Revision as of 18:33, 18 October 2016

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118 regimens on this page 227 variants on this page

Adjuvant therapy

Carboplatin & Paclitaxel

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Regimen

Study	Evidence	Comparator	Efficacy
Strauss et al. 2008 (CALGB 9633)	Phase III	Observation	Seems not superior

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV over 45 to 60 minutes once on day 1
Paclitaxel (Taxol) 200 mg/m² IV over 3 hours once on day 1

21-day cycle for 4 cycles

References

Strauss GM, Herndon JE 2nd, Maddaus MA, Johnstone DW, Johnson EA, Harpole DH, Gillenwater HH, Watson DM, Sugarbaker DJ, Schilsky RL, Vokes EE, Green MR. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol. 2008 Nov 1;26(31):5043-51. Epub 2008 Sep 22. link to original article contains protocol PubMed

Cisplatin & Docetaxel

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Example orders

Example orders for adjuvant Cisplatin (Platinol) and Docetaxel (Taxotere) in non-small cell lung cancer

Regimen

Study	Evidence	Comparator	Efficacy
Barlesi et al. 2015	Phase III	Cisplatin & Gemcitabine	Seems not superior

Treatment begins within 8 weeks of complete R0 resection for Stage IB–III NSCLC.

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV once on day 1
Docetaxel (Taxotere) 75 mg/m² IV once on day 1

21-day cycle for 3 cycles

References

Barlesi F, Chouaid C, Crequit J, Le Caer H, Pujol JL, Legodec J, Vergnenegre A, Le Treut J, Fabre-Guillevin E, Loundou A, Auquier P, Simeoni MC, Thomas PA. A randomized trial comparing adjuvant chemotherapy with gemcitabine plus cisplatin with docetaxel plus cisplatin in patients with completely resected non-small-cell lung cancer with quality of life as the primary objective. Interact Cardiovasc Thorac Surg. 2015 Jun;20(6):783-90. Epub 2015 Mar 11. link to original article contains verified protocol PubMed

Cisplatin & Etoposide

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Regimen

Study	Evidence	Comparator	Efficacy
Arriagada et al. 2004	Phase III	Observation	Seems to have superior OS

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV once on day 1
Etoposide (Vepesid) 100 mg/m² IV once per day on days 1 to 3

28-day cycle for 4 cycles

References

Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. link to original article PubMed

Cisplatin & Gemcitabine

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Regimen

Study	Evidence	Comparator	Efficacy
Barlesi et al. 2015	Phase III	Cisplatin & Docetaxel	Seems not superior

Treatment begins within 8 weeks of complete R0 resection for Stage IB–III NSCLC.

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV once on day 1
Gemcitabine (Gemzar) 1250 mg/m² IV once per day on days 1 & 8

21-day cycle for 3 cycles

References

Barlesi F, Chouaid C, Crequit J, Le Caer H, Pujol JL, Legodec J, Vergnenegre A, Le Treut J, Fabre-Guillevin E, Loundou A, Auquier P, Simeoni MC, Thomas PA. A randomized trial comparing adjuvant chemotherapy with gemcitabine plus cisplatin with docetaxel plus cisplatin in patients with completely resected non-small-cell lung cancer with quality of life as the primary objective. Interact Cardiovasc Thorac Surg. 2015 Jun;20(6):783-90. Epub 2015 Mar 11. link to original article contains verified protocol PubMed

Cisplatin & Pemetrexed

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Regimen

Study	Evidence	Comparator	Efficacy
Kreuter et al. 2013 (TREAT)	Randomized Phase II	Cisplatin & Vinorelbine	Superior clinical feasibility rate

Treatment to begin within 4 to 6 weeks after complete resection of pathologically confirmed NSCLC stages (according to the TNM staging system version 6) IB, IIA, IIB or T3N1.

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV once on day 1
Pemetrexed (Alimta) 500 mg/m² IV once on day 1

21-day cycle for 4 cycles

References

Kreuter M, Vansteenkiste J, Fischer JR, Eberhardt W, Zabeck H, Kollmeier J, Serke M, Frickhofen N, Reck M, Engel-Riedel W, Neumann S, Thomeer M, Schumann C, De Leyn P, Graeter T, Stamatis G, Zuna I, Griesinger F, Thomas M; TREAT investigators. Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study. Ann Oncol. 2013 Apr;24(4):986-92. Epub 2012 Nov 15. link to original article contains verified protocol PubMed

Cisplatin & Vinblastine

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Regimen

Study	Evidence	Comparator	Efficacy
Arriagada et al. 2004	Phase III	Observation	Seems to have superior OS

Note: Exact days for parts of the regimen were not specified by Arriagada et al. 2004. This vinblastine schedule is extrapolated from regimen information in Table 1 in which vinblastine is said to be given "weekly from days 1 to 29" and "then every 2 weeks after day 43 until last cisplatin administration.

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV once per day on days 1, 22, 43, 64
Vinblastine (Velban) 4 mg/m² IV once per day on days 1, 8, 15, 22, 29, 43, 57

12-week course

References

Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. link to original article contains verified protocol PubMed

Cisplatin & Vindesine

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Regimen

Study	Evidence	Comparator	Efficacy
Arriagada et al. 2004	Phase III	Observation	Seems to have superior OS

Note: Exact days for parts of the regimen were not specified by Arriagada et al. 2004. This vindesine schedule is extrapolated from regimen information in Table 1 in which vindesine is said to be given "weekly from days 1 to 29" and "then every 2 weeks after day 43 until last cisplatin administration.

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV once per day on days 1, 22, 43, 64
Vindesine (Eldisine) 3 mg/m² IV once per day on days 1, 8, 15, 22, 29, 43, 57

12-week course

References

Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. link to original article contains verified protocol PubMed

Cisplatin & Vinorelbine

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Regimen #1

Study	Evidence	Comparator	Efficacy
Winton et al. 2005 (JBR.10)	Phase III	Observation	Seems to have superior OS
Kreuter et al. 2013 (TREAT)	Randomized Phase II	Cisplatin & Pemetrexed	Inferior clinical feasibility rate

Treatment in TREAT to begin within 4 to 6 weeks after complete resection of pathologically confirmed NSCLC stages (according to the TNM staging system version 6) IB, IIA, IIB or T3N1.

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV once per day on days 1 & 8
Vinorelbine (Navelbine) 25 mg/m² IV once per day on days 1, 8, 15, 22

28-day cycle for 4 cycles

Regimen #2

Study	Evidence	Comparator	Efficacy
Arriagada et al. 2004	Phase III	Observation	Seems to have superior OS
Douillard et al. 2006 (ANITA)	Phase III	Observation	Seems to have superior OS

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV once on day 1
Vinorelbine (Navelbine) 30 mg/m² IV once per day on days 1, 8, 15, 22

28-day cycle for 4 cycles

Regimen #3

Study	Evidence
Hotta et al. 2001	Phase II

Chemotherapy

Cisplatin (Platinol) 75 to 80 mg/m² IV once on day 1
Vinorelbine (Navelbine) 25 to 30 mg/m² IV once per day on days 1 & 8

21-day cycle for 4 cycles

References

Hotta K, Sekine I, Tamura T, Sawada M, Watanabe H, Kusaba H, Akiyama Y, Inoue A, Shimoyama T, Nokihara H, Ueda Y, Yamamoto N, Kunitoh H, Ohe Y, Kodama T, Saijo N. A phase I/II study of cisplatin and vinorelbine chemotherapy in patients with advanced non-small cell lung cancer. Jpn J Clin Oncol. 2001 Dec;31(12):596-600. link to original article contains protocol PubMed
Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. link to original article PubMed content property of HemOnc.org
Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, Cormier Y, Goss G, Inculet R, Vallieres E, Fry W, Bethune D, Ayoub J, Ding K, Seymour L, Graham B, Tsao MS, Gandara D, Kesler K, Demmy T, Shepherd F; National Cancer Institute of Canada Clinical Trials Group; National Cancer Institute of the United States Intergroup JBR.10 Trial Investigators. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med. 2005 Jun 23;352(25):2589-97. link to original article PubMed
Douillard JY, Rosell R, De Lena M, Carpagnano F, Ramlau R, Gonzáles-Larriba JL, Grodzki T, Pereira JR, Le Groumellec A, Lorusso V, Clary C, Torres AJ, Dahabreh J, Souquet PJ, Astudillo J, Fournel P, Artal-Cortes A, Jassem J, Koubkova L, His P, Riggi M, Hurteloup P. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol. 2006 Sep;7(9):719-27. link to original article PubMed
Kreuter M, Vansteenkiste J, Fischer JR, Eberhardt W, Zabeck H, Kollmeier J, Serke M, Frickhofen N, Reck M, Engel-Riedel W, Neumann S, Thomeer M, Schumann C, De Leyn P, Graeter T, Stamatis G, Zuna I, Griesinger F, Thomas M; TREAT investigators. Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study. Ann Oncol. 2013 Apr;24(4):986-92. Epub 2012 Nov 15. link to original article contains verified protocol PubMed

Placebo (Observation)

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Regimen

Study	Evidence	Comparator	Efficacy
Arriagada et al. 2004	Phase III	Cisplatin & Etoposide	Seems to have inferior OS
		Cisplatin & Vinblastine	Seems to have inferior OS
		Cisplatin & Vindesine	Seems to have inferior OS
		Cisplatin & Vinorelbine	Seems to have inferior OS
Winton et al. 2006 (JBR.10)	Phase III	Cisplatin & Vinorelbine	Seems to have inferior OS
Douillard et al. 2006 (ANITA)	Phase III	Cisplatin & Vinorelbine	Seems to have inferior OS
Strauss et al. 2008 (CALGB 9633)	Phase III	Carboplatin & Paclitaxel	Seems not superior

No treatment. Placed here because one or more randomized clinical trials included a placebo or observation arm in this disease context.

References

Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. link to original article PubMed
Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, Cormier Y, Goss G, Inculet R, Vallieres E, Fry W, Bethune D, Ayoub J, Ding K, Seymour L, Graham B, Tsao MS, Gandara D, Kesler K, Demmy T, Shepherd F; National Cancer Institute of Canada Clinical Trials Group; National Cancer Institute of the United States Intergroup JBR.10 Trial Investigators. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med. 2005 Jun 23;352(25):2589-97. link to original article PubMed
Douillard JY, Rosell R, De Lena M, Carpagnano F, Ramlau R, Gonzáles-Larriba JL, Grodzki T, Pereira JR, Le Groumellec A, Lorusso V, Clary C, Torres AJ, Dahabreh J, Souquet PJ, Astudillo J, Fournel P, Artal-Cortes A, Jassem J, Koubkova L, His P, Riggi M, Hurteloup P. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol. 2006 Sep;7(9):719-27. link to original article PubMed
Strauss GM, Herndon JE 2nd, Maddaus MA, Johnstone DW, Johnson EA, Harpole DH, Gillenwater HH, Watson DM, Sugarbaker DJ, Schilsky RL, Vokes EE, Green MR. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol. 2008 Nov 1;26(31):5043-51. Epub 2008 Sep 22. link to original article contains protocol PubMed

Chemotherapy & radiation therapy

Carboplatin, Paclitaxel, concurrent RT

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Regimen

Study	Evidence
Belani et al. 2005	Phase II

Note: This regimen is listed by the NCCN, Non-Small Cell Lung Cancer version 2.2012, but this differs from the Belani et al. 2005 reference, in which additional consolidation chemotherapy is given after completion of concurrent chemotherapy & radiation therapy. That regimen is detailed here.

Chemotherapy

Carboplatin (Paraplatin) AUC 2 IV over 30 minutes once per day on days 1, 8, 15, given second
Paclitaxel (Taxol) 45 mg/m² IV over 1 hour once per day on days 1, 8, 15, given first

21-day cycle for 2 cycles, given with concurrent radiation therapy

Concurrent radiation therapy

Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions (total dose: 45 Gy), given once per day 5 days per week, then 2 Gy fractions x 9 fractions (additional dose: 18 Gy), given once per day 5 days per week. Total dose: 63 Gy over a total 7 week course of treatment.

References

Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. link to original article contains protocol PubMed

Carboplatin, Paclitaxel, concurrent RT -> consolidation chemo

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Regimen

Study	Evidence
Belani et al. 2005	Phase II

Chemoradiotherapy

Carboplatin (Paraplatin) AUC 2 IV over 30 minutes once per day on days 1, 8, 15, given second
Paclitaxel (Taxol) 45 mg/m² IV over 1 hour once per day on days 1, 8, 15, given first

21-day cycle for 2 cycles, given with concurrent radiation therapy

Concurrent radiation therapy

Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions (total dose: 45 Gy), given once per day 5 days per week, then 2 Gy fractions x 9 fractions (additional dose: 18 Gy), given once per day 5 days per week. Total dose: 63 Gy over a total 7 week course of treatment.

Consolidation chemotherapy

Carboplatin (Paraplatin) AUC 6 IV over 30 minutes once on day 1, given second
Paclitaxel (Taxol) 200 mg/m² IV over 3 hours once on day 1, given first

21-day cycle for 2 cycles

References

Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. link to original article contains protocol PubMed

Carboplatin, Paclitaxel -> sequential RT

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Regimen

Study	Evidence
Belani et al. 2005	Phase II

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV over 30 minutes once on day 1, given second
Paclitaxel (Taxol) 200 mg/m² IV over 3 hours once on day 1, given first

21-day cycle for 2 cycles, then proceed to radiation therapy

Radiation therapy

Sequential radiation therapy, 1.8 Gy fractions x 25 fractions (total dose: 45 Gy), given once per day 5 days per week, then 2 Gy fractions x 9 fractions (additional dose: 18 Gy), given once per day 5 days per week. Total dose: 63 Gy over a total 7 week course of treatment.

References

Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. link to original article contains protocol PubMed

Cisplatin, Etoposide, concurrent RT

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Regimen #1

Study	Evidence	Comparator	Efficacy
Curran et al. 2011 (RTOG 9410)	Phase III	Cisplatin, Vinblastine, concurrent RT	Seems not superior
Curran et al. 2011 (RTOG 9410)	Phase III	Cisplatin, Vinblastine, sequential RT	Might have superior OS

Chemoradiotherapy

Cisplatin (Platinol) 50 mg/m² IV once per day on days 1, 8, 29, 36
Etoposide (Vepesid) 50 mg PO BID on days 1 to 5, 8 to 12, 29 to 33, 36 to 40
Concurrent radiation therapy, 1.2 Gy fractions (total dose: 69.6 Gy), given twice per day for 5 days per week, starting on day 1

5-week course

Regimen #2

Study	Evidence
Albain et al. 2002 (SWOG 9019)	Phase II

Chemoradiotherapy

Cisplatin (Platinol) 50 mg/m² IV once per day on days 1, 8, 29, 36
Etoposide (Vepesid) 50 mg/m² IV once per day on days 1 to 5, 29 to 33
Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions (total dose: 45 Gy), given 5 days per week, to start within 24 hours of chemotherapy

5-week initial course of chemoradiotherapy

Patients were reimaged with CT scan (bone scan and head imaging were only done if patients had new symptoms), and those without progression or new metastatic disease received an additional 2 Gy per day x 8 fractions for a total of 61 Gy administered overall.

References

Albain KS, Crowley JJ, Turrisi AT 3rd, Gandara DR, Farrar WB, Clark JI, Beasley KR, Livingston RB. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: a Southwest Oncology Group phase II study, SWOG 9019. J Clin Oncol. 2002 Aug 15;20(16):3454-60. link to original article contains protocol PubMed
Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. link to original article PubMed

Cisplatin, Etoposide, concurrent RT -> consolidation chemo

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Regimen

Study	Evidence
Albain et al. 2002 (SWOG 9019)	Phase II

Note: The NCCN, Non-Small Cell Lung Cancer version 2.2012, describes "two extra cycles" of chemotherapy being given after completion of concurrent RT, but no primary reference can be found for this. It is unclear what the length of each cycle is supposed to be.

Chemoradiotherapy

Cisplatin (Platinol) 50 mg/m² IV once per day on days 1, 8, 29, 36
Etoposide (Vepesid) 50 mg/m² IV once per day on days 1 to 5, 29 to 33
Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions (total dose: 45 Gy), given 5 days per week, to start within 24 hours of chemotherapy

5-week initial course of chemotherapy & radiation; patients were reimaged with CT scan (bone scan and head imaging were only done if patients had new symptoms), and those without progression or new metastatic disease received an additional 2 Gy per day x 8 fractions for a total of 61 Gy administered overall

Consolidation chemotherapy

Cisplatin (Platinol) 50 mg/m² IV once per day on days 1 & 8
Etoposide (Vepesid) 50 mg/m² IV once per day on days 1 to 5

28-day cycle for 2 cycles

References

Albain KS, Crowley JJ, Turrisi AT 3rd, Gandara DR, Farrar WB, Clark JI, Beasley KR, Livingston RB. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: a Southwest Oncology Group phase II study, SWOG 9019. J Clin Oncol. 2002 Aug 15;20(16):3454-60. link to original article contains protocol--see note above PubMed

Cisplatin, Vinblastine, concurrent RT

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Regimen

Study	Evidence	Comparator	Efficacy
Curran et al. 2011 (RTOG 9410)	Phase III	Cisplatin, Etoposide, concurrent RT	Seems not superior
Curran et al. 2011 (RTOG 9410)	Phase III	Cisplatin, Vinblastine, sequential RT	Seems to have superior OS

Chemoradiotherapy

Cisplatin (Platinol) 100 mg/m² IV once per day on days 1 & 29
Vinblastine (Velban) 5 mg/m² IV once per day on days 1, 8, 15, 22, 29
Concurrent radiation therapy

5-week course of chemotherapy

References

Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. link to original article PubMed

Cisplatin, Vinblastine, sequential RT

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Regimen

Study	Evidence	Comparator	Efficacy
Curran et al. 2011 (RTOG 9410)	Phase III	Cisplatin, Etoposide, concurrent RT	Might have inferior OS
Curran et al. 2011 (RTOG 9410)	Phase III	Cisplatin, Vinblastine, concurrent RT	Seems to have inferior OS

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV once per day on days 1 & 29
Vinblastine (Velban) 5 mg/m² IV once per day on days 1, 8, 15, 22, 29

5-week total course of chemotherapy

Radiation therapy given after chemotherapy is complete

References

Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. link to original article PubMed

Advanced or metastatic disease, ALK-positive

Alectinib (Alecensa)

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Regimen

Study	Evidence
Ou et al. 2015 (NP28673)	Phase II
Gandhi et al. 2015 (NP28761)	Phase II

Patients in NP28673 and NP28761 were ALK mutation positive and had progression of disease on Crizotinib (Xalkori).

Chemotherapy

Alectinib (Alecensa) 600 mg PO BID, to be taken within 30 minutes of eating

Given until progressive disease, unacceptable toxicity, or withdrawal of consent

References

Leena Gandhi, Alice Shaw, Shirish M. Gadgeel, Gregory Riely, Jeremy Cetnar, Howard Jack West, D. Ross Camidge, Mark A. Socinski, Alberto Chiappori, Tarek Mekhail, Bo H. Chao, Hossein Borghaei, Kathryn A. Gold, Ali Hassan Zeaiter, Walter Bordogna, Bogdana Balas, Oscar Puig, Volkmar Henschel, Sai-Hong Ignatius Ou, NP28761 Study Investigators. A phase II, open-label, multicenter study of the ALK inhibitor alectinib in an ALK+ non-small-cell lung cancer (NSCLC) U.S./Canadian population who had progressed on crizotinib (NP28761). 2015 ASCO Annual Meeting abstract 8019. link to abstract
Ou SI, Ahn JS, De Petris L, Govindan R, Yang JC, Hughes B, Lena H, Moro-Sibilot D, Bearz A, Ramirez SV, Mekhail T, Spira A, Bordogna W, Balas B, Morcos PN, Monnet A, Zeaiter A, Kim DW. Alectinib in Crizotinib-Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global Study. J Clin Oncol. 2015 Nov 23. link to original article contains verified protocol PubMed

Ceritinib (Zykadia)

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Regimen

Study	Evidence
Shaw et al. 2014	Phase I

Shaw et al. 2014 investigated dose levels of 50 to 750 mg daily; 750 mg is the FDA-approved dose.

Chemotherapy

Ceritinib (Zykadia) 750 mg PO once per day on an empty stomach

Given until progression of disease

References

Shaw AT, Kim DW, Mehra R, Tan DS, Felip E, Chow LQ, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Lau YY, Goldwasser M, Boral AL, Engelman JA. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Mar 27;370(13):1189-97. link to original article contains verified protocol PubMed

Crizotinib (Xalkori)

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Regimen

Study	Evidence	Comparator	Efficacy
Kwak et al. 2010	Phase II
Shaw et al. 2013	Phase III	Pemetrexed	Superior PFS
Shaw et al. 2013	Phase III	Docetaxel	Superior PFS

Chemotherapy

Crizotinib (Xalkori) 250 mg PO BID on days 1 to 28

28-day cycles, given until progression of disease or unacceptable toxicity

Shaw et al. 2013 used 21-day cycles, and crizotinib was similarly given 250 mg PO BID on all days.

References

Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Jänne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, Iafrate AJ. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010 Oct 28;363(18):1693-703. link to original article contains verified protocol PubMed
1. Update: Camidge DR, Bang YJ, Kwak EL, Iafrate AJ, Varella-Garcia M, Fox SB, Riely GJ, Solomon B, Ou SH, Kim DW, Salgia R, Fidias P, Engelman JA, Gandhi L, Jänne PA, Costa DB, Shapiro GI, Lorusso P, Ruffner K, Stephenson P, Tang Y, Wilner K, Clark JW, Shaw AT. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol. 2012 Oct;13(10):1011-9. Epub 2012 Sep 4. link to original article contains verified protocol PubMed
Retrospective: Shaw AT, Yeap BY, Solomon BJ, Riely GJ, Gainor J, Engelman JA, Shapiro GI, Costa DB, Ou SH, Butaney M, Salgia R, Maki RG, Varella-Garcia M, Doebele RC, Bang YJ, Kulig K, Selaru P, Tang Y, Wilner KD, Kwak EL, Clark JW, Iafrate AJ, Camidge DR. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol. 2011 Oct;12(11):1004-12. Epub 2011 Sep 18. link to original article PubMed
Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O'Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Jänne PA. Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer. N Engl J Med. 2013 Jun 20;368(25):2385-94. Epub 2013 Jun 1. link to original article link to supplementary appendix contains verified protocol PubMed

Advanced or metastatic disease

Afatinib (Gliotrif)

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Regimen #1

Study	Evidence	Comparator	Efficacy
Yang et al. 2012 (LUX-Lung 2)	Phase II
Sequist et al. 2013 (LUX-Lung 3)	Phase III	Cisplatin & Pemetrexed	Superior PFS
Soria et al. 2015 (LUX-Lung 8)	Phase III	Erlotinib	Seems to have superior OS
Park et al. 2016 (LUX-Lung 7)	Randomized Phase II	Gefitinib	Seems to have superior PFS

Chemotherapy

Afatinib (Gliotrif) 40 mg PO once per day, given 1 hour before eating food (Yang et al. 2012: "no food intake immediately before or after afatinib")
- In LUX-Lung 3, patients could be increased to 50 mg PO once per day if they did not experience any grade 2 or higher rash, diarrhea, mucositis, or other drug-related adverse event.

Given until progressive disease, unacceptable toxicity, or withdrawal of consent

Regimen #2

Study	Evidence	Comparator	Efficacy
Miller et al. 2012 (LUX-Lung 1)	Phase III	Placebo	Superior PFS
Katakami et al. 2013 (LUX-Lung 4)	Phase II

In LUX-Lung 4, 72.6% of patients were EGFR mutation positive. This was third or fourth line therapy for participants, who had progressed while receiving erlotinib and/or gefitinib and had received one or two previous lines of chemotherapy, including at least one platinum-based regimen.

Chemotherapy

Afatinib (Gliotrif) 50 mg PO once per day, given 1 hour before eating food

Given until progressive disease, unacceptable toxicity, or withdrawal of consent

References

Miller VA, Hirsh V, Cadranel J, Chen YM, Park K, Kim SW, Zhou C, Su WC, Wang M, Sun Y, Heo DS, Crino L, Tan EH, Chao TY, Shahidi M, Cong XJ, Lorence RM, Yang JC. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol. 2012 May;13(5):528-38. Epub 2012 Mar 26. link to original article contains verified protocol PubMed
Yang JC, Shih JY, Su WC, Hsia TC, Tsai CM, Ou SH, Yu CJ, Chang GC, Ho CL, Sequist LV, Dudek AZ, Shahidi M, Cong XJ, Lorence RM, Yang PC, Miller VA. Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol. 2012 May;13(5):539-48. Epub 2012 Mar 26. link to original article contains verified protocol PubMed
Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. Epub 2013 Jul 1. link to original article contains verified protocol PubMed
1. Subgroup analysis: Yang JC, Hirsh V, Schuler M, Yamamoto N, O'Byrne KJ, Mok TS, Zazulina V, Shahidi M, Lungershausen J, Massey D, Palmer M, Sequist LV. Symptom Control and Quality of Life in LUX-Lung 3: A Phase III Study of Afatinib or Cisplatin/Pemetrexed in Patients With Advanced Lung Adenocarcinoma With EGFR Mutations. J Clin Oncol. 2013 Sep 20;31(27):3342-50. Epub 2013 Jul 1. link to original article contains verified protocol PubMed
Katakami N, Atagi S, Goto K, Hida T, Horai T, Inoue A, Ichinose Y, Koboyashi K, Takeda K, Kiura K, Nishio K, Seki Y, Ebisawa R, Shahidi M, Yamamoto N. LUX-Lung 4: A Phase II Trial of Afatinib in Patients With Advanced Non-Small-Cell Lung Cancer Who Progressed During Prior Treatment With Erlotinib, Gefitinib, or Both. J Clin Oncol. 2013 Sep 20;31(27):3335-41. Epub 2013 Jul 1. link to original article contains verified protocol PubMed
Soria JC, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, Göker E, Georgoulias V, Li W, Isla D, Guclu SZ, Morabito A, Min YJ, Ardizzoni A, Gadgeel SM, Wang B, Chand VK, Goss GD; LUX-Lung 8 Investigators. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015 Aug;16(8):897-907. Epub 2015 Jul 5. link to original article contains protocol PubMed
Park K, Tan EH, O'Byrne K, Zhang L, Boyer M, Mok T, Hirsh V, Yang JC, Lee KH, Lu S, Shi Y, Kim SW, Laskin J, Kim DW, Arvis CD, Kölbeck K, Laurie SA, Tsai CM, Shahidi M, Kim M, Massey D, Zazulina V, Paz-Ares L. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016 May;17(5):577-89. Epub 2016 Apr 12. link to original article contains protocol PubMed

Atezolizumab (Tecentriq)

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Regimen

Study	Evidence	Comparator	Efficacy
Fehrenbacher et al. 2016 (POPLAR)	Randomized Phase II	Docetaxel	Seems to have superior OS

Immunotherapy

Atezolizumab (Tecentriq) 1200 mg IV once on day 1

3-week cycles

References

Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, Park K, Smith D, Artal-Cortes A, Lewanski C, Braiteh F, Waterkamp D, He P, Zou W, Chen DS, Yi J, Sandler A, Rittmeyer A; POPLAR Study Group. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016 Apr 30;387(10030):1837-46. Epub 2016 Mar 9. link to original article contains protocol PubMed

Carboplatin & Docetaxel

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Regimen

Study	Evidence	Comparator	Efficacy
Fossella et al. 2003 (TAX 326)	Phase III	Cisplatin & Docetaxel
Fossella et al. 2003 (TAX 326)	Phase III	Cisplatin & Vinorelbine	Seems not superior

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1
Docetaxel (Taxotere) 75 mg/m² IV once on day 1

21-day cycles

References

Fossella F, Pereira JR, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003 Aug 15;21(16):3016-24. Epub 2003 Jul 1. link to original article contains protocol PubMed

Carboplatin & Gemcitabine

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Regimen

Study	Evidence	Comparator	Efficacy
Sederholm et al. 2005	Phase III	Gemcitabine	Seems to have superior OS
Grønberg et al. 2009	Phase III	Carboplatin & Pemetrexed	Seems not superior
Zhou et al. 2011 (OPTIMAL, CTONG-0802)	Phase III	Erlotinib	Inferior PFS

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV once on day 1
Gemcitabine (Gemzar) 1000 to 1250 mg/m² IV once per day on days 1 & 8

21-day cycles

References

Sederholm C, Hillerdal G, Lamberg K, Kölbeck K, Dufmats M, Westberg R, Gawande SR. Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group. J Clin Oncol. 2005 Nov 20;23(33):8380-8. link to original article contains verified protocol PubMed
Grønberg BH, Bremnes RM, Fløtten O, Amundsen T, Brunsvig PF, Hjelde HH, Kaasa S, von Plessen C, Stornes F, Tollåli T, Wammer F, Aasebø U, Sundstrøm S. Phase III study by the Norwegian lung cancer study group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2009 Jul 1;27(19):3217-24. Epub 2009 May 11. link to original article contains protocol PubMed
Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011 Aug;12(8):735-42. Epub 2011 Jul 23. link to original article PubMed
1. Update: Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015 Sep;26(9):1877-83. Epub 2015 Jul 3. link to original article PubMed

Carboplatin & Paclitaxel

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Regimen #1

Study	Evidence	Comparator	Efficacy
Johnson et al. 2004	Randomized Phase II	PacCBev	Seems to have inferior TTP
Sandler et al. 2006 (ECOG 4599)	Phase III	PacCBev -> Maintenance Bev	Inferior OS
Lilenbaum et al. 2008	Phase III	Erlotinib	Seems to have superior OS
Mok et al. 2009 (IPASS)	Phase III	Gefitinib	Inferior PFS
Socinski et al. 2012	Phase III	Carboplatin & nabPaclitaxel	Inferior ORR
Langer et al. 2014	Phase III	Carboplatin, Figitumumab, Paclitaxel	Might have superior OS

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV over 15 to 60 minutes once on day 1, given second
Paclitaxel (Taxol) 200 mg/m² IV over 3 hours once on day 1, given first

21-day cycle for 4 to 6 cycles

Patients in Socinski et al. 2012 "could continue in the absence of progressive disease and unacceptable toxicity per the investigator's discretion."

Regimen #2

Study	Evidence	Comparator	Efficacy
Lynch et al. 2012	Randomized Phase II	Carboplatin, Paclitaxel, Ipilimumab	Seems to have inferior PFS

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1
Paclitaxel (Taxol) 175 mg/m² IV once on day 1

Supportive medications

Corticosteroids could be used as premedication for paclitaxel infusion.

21-day cycle for up to 6 cycles

Regimen #3, weekly paclitaxel

Study	Evidence	Comparator	Efficacy
Quoix et al. 2011 (IFCT-0501)	Phase III	Gemcitabine	Superior OS
Quoix et al. 2011 (IFCT-0501)	Phase III	Vinorelbine	Superior OS

Study involved only patients 70 to 89 years old

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1
Paclitaxel (Taxol) 90 mg/m² IV once per day on days 1, 8, 15

Supportive medications

Growth factor support was not recommended as primary prophylaxis during cycle 1, but could be used if the patient develops grade 3-4 neutropenia

28-day cycle for up to 4 cycles

Regimen #4

Study	Evidence	Comparator	Efficacy
Mok et al. 2009 (IPASS)	Phase III	Gefitinib	Inferior PFS

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV over 15 to 60 minutes once on day 1, given second
Paclitaxel (Taxol) 200 mg/m² IV over 3 hours once on day 1, given first

21-day cycle for 6 cycles

Regimen #5

Study	Evidence	Comparator	Efficacy
Schiller et al. 2002	Phase III	Cisplatin & Docetaxel	Seems not superior
		Cisplatin & Gemcitabine	Seems not superior
		Cisplatin & Paclitaxel	Seems not superior

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1, given second
Paclitaxel (Taxol) 225 mg/m² IV over 3 hours once on day 1, given first

21-day cycles

References

Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. link to original article contains protocol PubMed
Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, Langer CJ, DeVore RF 3rd, Gaudreault J, Damico LA, Holmgren E, Kabbinavar F. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2004 Jun 1;22(11):2184-91. link to original article PubMed
Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14;355(24):2542-50. link to original article contains verified protocol PubMed
1. Subset analysis: Ramalingam SS, Dahlberg SE, Langer CJ, Gray R, Belani CP, Brahmer JR, Sandler AB, Schiller JH, Johnson DH; Eastern Cooperative Oncology Group. Outcomes for elderly, advanced-stage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol. 2008 Jan 1;26(1):60-5. link to original article contains verified protocol PubMed
Lilenbaum R, Axelrod R, Thomas S, Dowlati A, Seigel L, Albert D, Witt K, Botkin D. Randomized phase II trial of erlotinib or standard chemotherapy in patients with advanced non-small-cell lung cancer and a performance status of 2. J Clin Oncol. 2008 Feb 20;26(6):863-9. link to original article contains protocol PubMed
Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947-57. Epub 2009 Aug 19. link to original article contains verified protocol PubMed
Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, Dauba J, Debieuvre D, Souquet PJ, Bigay-Game L, Dansin E, Poudenx M, Molinier O, Vaylet F, Moro-Sibilot D, Herman D, Bennouna J, Tredaniel J, Ducoloné A, Lebitasy MP, Baudrin L, Laporte S, Milleron B; Intergroupe Francophone de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17;378(9796):1079-88. Epub 2011 Aug 8. link to original article contains verified protocol PubMed
Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012 Jun 10;30(17):2046-54. Epub 2012 Apr 30. link to original article contains verified protocol PubMed
Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, Hon JK, Hirsh V, Bhar P, Zhang H, Iglesias JL, Renschler MF. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2055-62. Epub 2012 Apr 30. link to original article contains verified protocol PubMed
Langer CJ, Novello S, Park K, Krzakowski M, Karp DD, Mok T, Benner RJ, Scranton JR, Olszanski AJ, Jassem J. Randomized, phase III trial of first-line figitumumab in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin alone in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2014 Jul 1;32(19):2059-66. Epub 2014 Jun 2. link to original article PubMed

Carboplatin & Paclitaxel, nanoparticle albumin-bound

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Regimen

Study	Evidence	Comparator	Efficacy
Socinski et al. 2012	Phase III	Carboplatin & Paclitaxel	Superior ORR

Chemotherapy

Carboplatin (Paraplatin) AUC 6 mg/mL/min (per Calvert formula) IV once on day 1, given second
Paclitaxel, nanoparticle albumin-bound (Abraxane) 100 mg/m² IV over 30 minutes once per day on days 1, 8, 15, given first

21-day cycle for 6 cycles; treatment could continue at physician's discretion if there was no progressive disease or unacceptable toxicity

References

Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, Hon JK, Hirsh V, Bhar P, Zhang H, Iglesias JL, Renschler MF. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2055-62. Epub 2012 Apr 30. link to original article contains verified protocol PubMed

Carboplatin, Paclitaxel, Bevacizumab (PacCBev)

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PacCBev: Paclitaxel, Carboplatin, Bevacizumab

Regimen #1

Study	Evidence	Comparator	Efficacy
Patel et al. 2013 (PointBreak)	Phase III	PemCBev -> Maintenance PemBev	Seems to have inferior PFS

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1
Paclitaxel (Taxol) 200 mg/m² IV once on day 1
Bevacizumab (Avastin) 15 mg/kg IV once on day 1

Supportive medications

Premedications per paclitaxel label
Erythropoietic agents or granulocyte colony-stimulating factors allowed per ASCO & NCCN guidelines

21-day cycle for 4 cycles

Patients with complete response, partial response, or stable disease proceeded to bevacizumab maintenance therapy.

Regimen #2

Study	Evidence	Comparator	Efficacy
Johnson et al. 2004	Randomized Phase II	Carboplatin & Paclitaxel	Seems to have superior TTP
Sandler et al. 2006 (ECOG 4599)	Phase III	Carboplatin & Paclitaxel	Superior OS

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV over 15 to 30 minutes once on day 1, given second, starting 60 minutes after the completion of paclitaxel
Paclitaxel (Taxol) 200 mg/m² IV over 3 hours once on day 1, given first
Bevacizumab (Avastin) 15 mg/kg IV on day 1, given third, starting 60 minutes after the completion of carboplatin
- Infusion time for bevacizumab per Johnson, et al. 2004 was over 90 minutes for cycle 1; if tolerated, bevacizumab was given over 30 to 60 minutes for cycles 2 and later

21-day cycle for up to 6 cycles, or until progression of disease, or unacceptable toxicity

After 6 cycles, patients in ECOG 4599 who had stable disease or response continued to bevacizumab maintenance therapy.

References

Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, Langer CJ, DeVore RF 3rd, Gaudreault J, Damico LA, Holmgren E, Kabbinavar F. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2004 Jun 1;22(11):2184-91. link to original article PubMed
Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14;355(24):2542-50. link to original article contains verified protocol PubMed
1. Subset analysis: Ramalingam SS, Dahlberg SE, Langer CJ, Gray R, Belani CP, Brahmer JR, Sandler AB, Schiller JH, Johnson DH; Eastern Cooperative Oncology Group. Outcomes for elderly, advanced-stage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol. 2008 Jan 1;26(1):60-5. link to original article contains verified protocol PubMed
Patel JD, Socinski MA, Garon EB, Reynolds CH, Spigel DR, Olsen MR, Hermann RC, Jotte RM, Beck T, Richards DA, Guba SC, Liu J, Frimodt-Moller B, John WJ, Obasaju CK, Pennella EJ, Bonomi P, Govindan R. PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. J Clin Oncol. 2013 Dec 1;31(34):4349-57. link to original article contains verified protocol PubMed

Carboplatin, Paclitaxel, Ipilimumab

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Regimen

Study	Evidence	Comparator	Efficacy
Lynch et al. 2012	Randomized Phase II	Carboplatin & Paclitaxel	Seems to have superior PFS

Note: this is the "phased" approach to this regimen.

Chemoimmunotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1
Paclitaxel (Taxol) 175 mg/m² IV once on day 1
Ipilimumab (Yervoy) as follows:
- Cycles 3 to 6: 10 mg/kg IV once on day 1

Supportive medications

Corticosteroids could be used as premedication for Paclitaxel (Taxol) infusion or for toxicity management.

21-day cycle for up to 6 cycles

Patients without progressive disease proceeded to receive maintenance ipilimumab therapy.

References

Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012 Jun 10;30(17):2046-54. Epub 2012 Apr 30. link to original article contains verified protocol PubMed

Carboplatin & Pemetrexed

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Example orders

Example orders for Carboplatin (Paraplatin) and Pemetrexed (Alimta) in non-small cell lung cancer

Regimen #1

Study	Evidence	Comparator	Efficacy
Ardizzoni et al. 2012 (GOIRC 02-2006)	Randomized Phase II	Pemetrexed	Seems not superior
Zukin et al. 2013	Phase III	Pemetrexed	Superior OS

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1, given second
Pemetrexed (Alimta) 500 mg/m² IV over 10 minutes once on day 1, given first

Supportive medications

(Ardizzoni et al. 2012 contained more details):
Dexamethasone (Decadron) 4 mg or equivalent corticosteroid PO BID on the day before, the day of, and day after each dose of pemetrexed
Folic acid 350 to 600 mcg PO once per day, starting 1 to 2 weeks before the first dose of pemetrexed, to be taken throughout pemetrexed therapy.
Cyanocobalamin (Vitamin B12) 1000 mcg IM once every 9 weeks, first dose 1 to 2 weeks before the first dose of pemetrexed, to be given throughout pemetrexed therapy

21-day cycle for up to 4 cycles or until progressive disease, unacceptable toxicity, or patient refusal

Regimen #2

Study	Evidence	Comparator	Efficacy
Grønberg et al. 2009	Phase III	Carboplatin & Gemcitabine	Seems not superior

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1
Pemetrexed (Alimta) 500 mg/m² IV once on day 1

Supportive medications

Cyanocobalamin (Vitamin B12) 1000 mcg IM once every 9 weeks, first dose prior to Pemetrexed (Alimta)
Folic acid 1 mg PO once per day

21-day cycles

References

Grønberg BH, Bremnes RM, Fløtten O, Amundsen T, Brunsvig PF, Hjelde HH, Kaasa S, von Plessen C, Stornes F, Tollåli T, Wammer F, Aasebø U, Sundstrøm S. Phase III study by the Norwegian lung cancer study group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2009 Jul 1;27(19):3217-24. Epub 2009 May 11. link to original article contains protocol PubMed
Ardizzoni A, Tiseo M, Boni L, Vincent AD, Passalacqua R, Buti S, Amoroso D, Camerini A, Labianca R, Genestreti G, Boni C, Ciuffreda L, Di Costanzo F, de Marinis F, Crinò L, Santo A, Pazzola A, Barbieri F, Zilembo N, Colantonio I, Tibaldi C, Mattioli R, Cafferata MA, Camisa R, Smit EF. Pemetrexed versus pemetrexed and carboplatin as second-line chemotherapy in advanced non-small-cell lung cancer: results of the GOIRC 02-2006 randomized phase II study and pooled analysis with the NVALT7 trial. J Clin Oncol. 2012 Dec 20;30(36):4501-7. Epub 2012 Oct 29. link to original article contains verified protocol PubMed
Zukin M, Barrios CH, Rodrigues Pereira J, De Albuquerque Ribeiro R, de Mendonça Beato CA, do Nascimento YN, Murad A, Franke FA, Precivale M, de Lima Araujo LH, Da Rocha Baldotto CS, Vieira FM, Small IA, Ferreira CG, Lilenbaum RC. Randomized Phase III Trial of Single-Agent Pemetrexed Versus Carboplatin and Pemetrexed in Patients With Advanced Non-Small-Cell Lung Cancer and Eastern Cooperative Oncology Group Performance Status of 2. J Clin Oncol. 2013 Aug 10;31(23):2849-53. Epub 2013 Jun 17. link to original article contains verified protocol PubMed

Carboplatin, Pemetrexed, Bevacizumab (PemCBev)

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PemCBev: Pemetrexed, Carboplatin, Bevacizumab

Regimen

Study	Evidence	Comparator	Efficacy
Patel et al. 2013 (PointBreak)	Phase III	PacCBev -> Maintenance Bev	Seems to have superior PFS

Chemotherapy

Carboplatin (Paraplatin) AUC 6 IV once on day 1
Pemetrexed (Alimta) 500 mg/m² IV once on day 1
Bevacizumab (Avastin) 15 mg/kg IV once on day 1

Supportive medications

Premedications, folic acid, and vitamin supplementation per pemetrexed label
Erythropoietic agents or granulocyte colony-stimulating factors allowed per ASCO & NCCN guidelines

21-day cycle for 4 cycles

Patients with complete response, partial response, or stable disease proceeded to bevacizumab & pemetrexed maintenance therapy.

References

Patel JD, Socinski MA, Garon EB, Reynolds CH, Spigel DR, Olsen MR, Hermann RC, Jotte RM, Beck T, Richards DA, Guba SC, Liu J, Frimodt-Moller B, John WJ, Obasaju CK, Pennella EJ, Bonomi P, Govindan R. PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. J Clin Oncol. 2013 Dec 1;31(34):4349-57. link to original article contains verified protocol PubMed

Cisplatin & Docetaxel

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Regimen

Study	Evidence	Comparator	Efficacy
Schiller et al. 2002	Phase III	Carboplatin & Paclitaxel	Seems not superior
		Cisplatin & Gemcitabine	Seems not superior
		Cisplatin & Paclitaxel	Seems not superior
Fossella et al. 2003 (TAX 326)	Phase III	Carboplatin & Docetaxel
Fossella et al. 2003 (TAX 326)	Phase III	Cisplatin & Vinorelbine	Seems to have superior OS

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV once on day 1
Docetaxel (Taxotere) 75 mg/m² IV once on day 1

21-day cycles

References

Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. link to original article contains protocol PubMed
Fossella F, Pereira JR, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003 Aug 15;21(16):3016-24. Epub 2003 Jul 1. link to original article contains protocol PubMed

Cisplatin & Gemcitabine

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Regimen #1

Study	Evidence	Comparator	Efficacy
Thatcher et al. 2015 (SQUIRE)	Phase III	Cisplatin, Gemcitabine, Necitumumab	Seems to have inferior OS

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV over 30 minutes once on day 1
Gemcitabine (Gemzar) 1250 mg/m² IV over 120 minutes once per day on days 1 & 8

21-day cycles

Regimen #2

Study	Evidence	Comparator	Efficacy
Schiller et al. 2002	Phase III	Carboplatin & Paclitaxel	Seems not superior
		Cisplatin & Docetaxel	Seems not superior
		Cisplatin & Paclitaxel	Superior PFS
Scagliotti et al. 2008	Phase III	Cisplatin & Pemetrexed	Seems non-inferior

Note: the subgroup of Scagliotti et al. 2008 with adenocarcinoma seemed to have superior OS with this regimen.

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV once on day 1
Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1, 8, 15

28-day cycles

References

Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. link to original article contains protocol PubMed
Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008 Jul 20;26(21):3543-51. Epub 2008 May 27. link to original article contains protocol PubMed
Thatcher N, Hirsch FR, Luft AV, Szczesna A, Ciuleanu TE, Dediu M, Ramlau R, Galiulin RK, Bálint B, Losonczy G, Kazarnowicz A, Park K, Schumann C, Reck M, Depenbrock H, Nanda S, Kruljac-Letunic A, Kurek R, Paz-Ares L, Socinski MA; SQUIRE Investigators. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2015 Jul;16(7):763-74. link to original article contains protocol PubMed

Cisplatin, Gemcitabine, Necitumumab

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Regimen

Study	Evidence	Comparator	Efficacy
Thatcher et al. 2015 (SQUIRE)	Phase III	Cisplatin & Gemcitabine	Seems to have superior OS

Patients had stage IV squamous non-small-cell lung cancer

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV over 120 minutes once on day 1
Gemcitabine (Gemzar) 1250 mg/m² IV over 30 minutes once per day on days 1 & 8
Necitumumab (Portrazza) 800 mg IV over at least 50 minutes once per day on days 1 & 8, before gemcitabine

Supportive medications

Antiemetic premedications for gemcitabine and cisplatin "according to local practice."
"Pre-emptive treatment for skin toxicity was allowed only after the first cycle."

21-day cycle for 6 cycles

Patients who were free of disease progression proceeded to maintenance necitumumab.

References

Thatcher N, Hirsch FR, Luft AV, Szczesna A, Ciuleanu TE, Dediu M, Ramlau R, Galiulin RK, Bálint B, Losonczy G, Kazarnowicz A, Park K, Schumann C, Reck M, Depenbrock H, Nanda S, Kruljac-Letunic A, Kurek R, Paz-Ares L, Socinski MA; SQUIRE Investigators. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2015 Jul;16(7):763-74. link to original article contains verified protocol PubMed

Cisplatin & Paclitaxel

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Regimen

Study	Evidence	Comparator	Efficacy
Schiller et al. 2002	Phase III	Carboplatin & Paclitaxel	Seems not superior
		Cisplatin & Docetaxel	Seems not superior
		Cisplatin & Gemcitabine	Inferior PFS

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV once on day 2, after paclitaxel
Paclitaxel (Taxol) 135 mg/m² IV continuous infusion over 24 hours once on day 1

21-day cycles

References

Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. link to original article contains verified protocol PubMed

Cisplatin & Pemetrexed

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Regimen #1

Study	Evidence	Comparator	Efficacy
Scagliotti et al. 2008	Phase III	Cisplatin & Gemcitabine	Seems non-inferior
Sequist et al. 2013 (LUX-Lung 3)	Phase III	Afatinib	Inferior PFS
Paz-Ares et al. 2015 (INSPIRE)	Phase III	Cisplatin, Pemetrexed, Necitumumab	Seems not superior

Note: the subgroup of Scagliotti et al. 2008 with adenocarcinoma seemed to have inferior OS with this regimen.

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV once on day 1
Pemetrexed (Alimta) 500 mg/m² IV once on day 1

Supportive medications

(as described in Scagliotti et al. 2008):
Cyanocobalamin (Vitamin B12) 1000 mcg IM every 9 weeks, first dose prior to Pemetrexed (Alimta)
Folic acid 1 mg PO once per day
In Sequist et al. 2013: Patients "received folic acid, vitamin B12, and dexamethasone, as per package recommendations for Pemetrexed (Alimta)."

21-day cycle for up to 6 cycles

Regimen #2

Study	Evidence
Paz-Ares et al. 2012 (PARAMOUNT)	Non-randomized portion of RCT

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV once on day 1
Pemetrexed (Alimta) 500 mg/m² IV once on day 1

Supportive medications

Folic acid, Cyanocobalamin (Vitamin B12), prophylactic Dexamethasone (Decadron)
"Investigators followed current American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) guidelines for use of colony-stimulating factors and erythropoiesis-stimulating agents."

21-day cycle for 4 cycles

Subsequently patients were randomized to placebo versus pemetrexed maintenance therapy.

References

Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008 Jul 20;26(21):3543-51. Epub 2008 May 27. link to original article contains protocol PubMed
Paz-Ares L, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2012 Mar;13(3):247-55. Epub 2012 Feb 16. link to original article contains verified protocol PubMed
1. Update: Paz-Ares LG, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. PARAMOUNT: Final Overall Survival Results of the Phase III Study of Maintenance Pemetrexed Versus Placebo Immediately After Induction Treatment With Pemetrexed Plus Cisplatin for Advanced Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2013 Aug 10;31(23):2895-902. Epub 2013 Jul 8. link to original article contains verified protocol PubMed
Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. Epub 2013 Jul 1. link to original article contains verified protocol PubMed
1. Subgroup analysis: Yang JC, Hirsh V, Schuler M, Yamamoto N, O'Byrne KJ, Mok TS, Zazulina V, Shahidi M, Lungershausen J, Massey D, Palmer M, Sequist LV. Symptom Control and Quality of Life in LUX-Lung 3: A Phase III Study of Afatinib or Cisplatin/Pemetrexed in Patients With Advanced Lung Adenocarcinoma With EGFR Mutations. J Clin Oncol. 2013 Sep 20;31(27):3342-50. Epub 2013 Jul 1. link to original article contains verified protocol PubMed
Paz-Ares L, Mezger J, Ciuleanu TE, Fischer JR, von Pawel J, Provencio M, Kazarnowicz A, Losonczy G, de Castro G Jr, Szczesna A, Crino L, Reck M, Ramlau R, Ulsperger E, Schumann C, Miziara JE, Lessa ÁE, Dediu M, Bálint B, Depenbrock H, Soldatenkova V, Kurek R, Hirsch FR, Thatcher N, Socinski MA; INSPIRE investigators. Necitumumab plus pemetrexed and cisplatin as first-line therapy in patients with stage IV non-squamous non-small-cell lung cancer (INSPIRE): an open-label, randomised, controlled phase 3 study. Lancet Oncol. 2015 Mar;16(3):328-37. Epub 2015 Feb 18. link to original article PubMed

Cisplatin, Pemetrexed, Bevacizumab

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Regimen

Study	Evidence
Barlesi et al. 2013 (AVAPERL (MO22089))	Phase II

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV over 2 hours once on day 1
Pemetrexed (Alimta) 500 mg/m² IV over 10 minutes once on day 1
Bevacizumab (Avastin) 7.5 mg/kg IV once on day 1; administered over 90 minutes for the first dose, and if well tolerated, subsequent infusions were given over 60 minutes, then 30 minutes

Supportive medications

Cyanocobalamin (Vitamin B12) 1000 mcg IM every 3 cycles (i.e. every 9 weeks), given throughout therapy
Folic acid 350 to 1000 mcg PO once per day, given throughout therapy
Dexamethasone (Decadron) 4 mg PO BID on days -1, 1, 2 of each cycle

21-day cycle for 4 cycles

Patients with complete response (CR), partial response (PR), or stable disease (SD) were randomized to bevacizumab maintenance versus bevacizumab & pemetrexed maintenance.

References

Barlesi F, Scherpereel A, Rittmeyer A, Pazzola A, Ferrer Tur N, Kim JH, Ahn MJ, Aerts JG, Gorbunova V, Vikström A, Wong EK, Perez-Moreno P, Mitchell L, Groen HJ. Randomized Phase III Trial of Maintenance Bevacizumab With or Without Pemetrexed After First-Line Induction With Bevacizumab, Cisplatin, and Pemetrexed in Advanced Nonsquamous Non-Small-Cell Lung Cancer: AVAPERL (MO22089). J Clin Oncol. 2013 Aug 20;31(24):3004-11. Epub 2013 Jul 8. link to original article contains verified protocol PubMed

Cisplatin & Vinorelbine

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Regimen #1

Study	Evidence	Comparator	Efficacy
Pirker et al. 2009 (FLEX)	Phase III	Cisplatin, Vinorelbine, Cetuximab	Seems to have inferior OS

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV once on day 1
Vinorelbine (Navelbine) 25 mg/m² IV once per day on days 1 & 8

21-day cycle for up to 6 cycles

Regimen #2

Study	Evidence	Comparator	Efficacy
Fossella et al. 2003 (TAX 326)	Phase III	Carboplatin & Docetaxel	Seems not superior
Fossella et al. 2003 (TAX 326)	Phase III	Cisplatin & Docetaxel	Seems to have inferior OS

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV once on day 1
Vinorelbine (Navelbine) 25 mg/m² IV once on day 1

28-day cycles

References

Fossella F, Pereira JR, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003 Aug 15;21(16):3016-24. Epub 2003 Jul 1. link to original article contains protocol PubMed
Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Yu CT, Ganul V, Roh JK, Bajetta E, O'Byrne K, de Marinis F, Eberhardt W, Goddemeier T, Emig M, Gatzemeier U; FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009 May 2;373(9674):1525-31. link to original article contains verified protocol PubMed

Cisplatin, Vinorelbine, Cetuximab

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Regimen

Study	Evidence	Comparator	Efficacy
Pirker et al. 2009 (FLEX)	Phase III	Cisplatin & Vinorelbine	Seems to have superior OS

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV once on day 1
Vinorelbine (Navelbine) 25 mg/m² IV once per day on days 1 & 8
Cetuximab (Erbitux) as follows:
- Week 1: 400 mg/m² IV over 2 hours once on day 1
- Week 2 onwards: 250 mg/m² over 1 hour once per week

21-day cycle for up to 6 cycles

Cetuximab was then to continue until progression or intolerable toxicity.

References

Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Yu CT, Ganul V, Roh JK, Bajetta E, O'Byrne K, de Marinis F, Eberhardt W, Goddemeier T, Emig M, Gatzemeier U; FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009 May 2;373(9674):1525-31. link to original article contains protocol PubMed

Docetaxel (Taxotere)

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Example orders

Example orders for Docetaxel (Taxotere) in non-small cell lung cancer

Regimen #1, 3-week docetaxel

Study	Evidence	Comparator	Efficacy
Hanna et al. 2004	Phase III	Pemetrexed	Inconclusive whether non-inferior
Chen et al. 2006	Phase III	Weekly paclitaxel
Kim et al. 2008 (INTEREST)	Phase III	Gefitinib	Seems non-inferior
Shaw et al. 2013	Phase III	Crizotinib	Inferior PFS
Reck et al. 2014 (LUME-Lung 1)	Phase III	Docetaxel & Nintedanib	Inferior PFS
Garon et al. 2014 (REVEL)	Phase III	Docetaxel & Ramucirumab	Seems to have inferior OS
Brahmer et al. 2015 (CheckMate 017)	Phase III	Nivolumab	Inferior OS
Borghaei et al. 2015 (CheckMate 057)	Phase III	Nivolumab	Inferior OS
Herbst et al. 2015 (KEYNOTE-010)	Phase II/III	Pembrolizumab	Inferior OS
Fehrenbacher et al. 2016 (POPLAR)	Randomized Phase II	Atezolizumab	Seems to have inferior OS

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV over 1 hour once on day 1
- In Garon, et al. 2014, East Asian patients were later recommended to receive Docetaxel (Taxotere) 60 mg/m² IV once on day 1

Supportive medications

Per Hanna et al. 2004: Dexamethasone (Decadron) 8 mg PO BID the day before, the day of, and the day after docetaxel
Per Chem et al. 2006: Dexamethasone (Decadron) 8 mg PO once 12 hours before docetaxel, 10 mg IV once 30 minutes before docetaxel, and 8 mg PO 12 hours after docetaxel

21-day cycles, given until progression of disease, unacceptable toxicity, or patient/physician choice

Regimen #2, weekly docetaxel

Study	Evidence	Comparator	Efficacy
Chen et al. 2006	Phase III	3-week docetaxel

Chemotherapy

Docetaxel (Taxotere) 35 mg/m² IV once per day on days 1, 8, 15

Supportive medications

Dexamethasone (Decadron) 8 mg PO once 12 hours before docetaxel, 10 mg IV once 30 minutes before docetaxel, and 8 mg PO 12 hours after docetaxel

28-day cycles

References

Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, Gatzemeier U, Tsao TC, Pless M, Muller T, Lim HL, Desch C, Szondy K, Gervais R, Shaharyar, Manegold C, Paul S, Paoletti P, Einhorn L, Bunn PA Jr. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004 May 1;22(9):1589-97. link to original article contains verified protocol PubMed
Chen YM, Shih JF, Perng RP, Tsai CM, Whang-Peng J. A randomized trial of different docetaxel schedules in non-small cell lung cancer patients who failed previous platinum-based chemotherapy. Chest. 2006 Apr;129(4):1031-8. link to SD article contains verified protocol PubMed
Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Wu YL, Li LY, Watkins CL, Sellers MV, Lowe ES, Sun Y, Liao ML, Osterlind K, Reck M, Armour AA, Shepherd FA, Lippman SM, Douillard JY. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet. 2008 Nov 22;372(9652):1809-18. link to original article contains protocol PubMed
Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O'Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Jänne PA. Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer. N Engl J Med. 2013 Jun 20;368(25):2385-94. Epub 2013 Jun 1. link to original article link to supplementary appendix contains verified protocol PubMed
Reck M, Kaiser R, Mellemgaard A, Douillard JY, Orlov S, Krzakowski M, von Pawel J, Gottfried M, Bondarenko I, Liao M, Gann CN, Barrueco J, Gaschler-Markefski B, Novello S; LUME-Lung 1 Study Group. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol. 2014 Feb;15(2):143-55. 2. Epub 2014 Jan 9. link to original article PubMed
Garon EB, Ciuleanu TE, Arrieta O, Prabhash K, Syrigos KN, Goksel T, Park K, Gorbunova V, Kowalyszyn RD, Pikiel J, Czyzewicz G, Orlov SV, Lewanski CR, Thomas M, Bidoli P, Dakhil S, Gans S, Kim JH, Grigorescu A, Karaseva N, Reck M, Cappuzzo F, Alexandris E, Sashegyi A, Yurasov S, Pérol M. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014 Aug 23;384(9944):665-73. link to original article contains verified protocol PubMed
Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Arén Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. Epub 2015 May 31. link to original article PubMed
Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhäufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crinò L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Oct 22;373(17):1627-39. Epub 2015 Sep 27. link to original article PubMed
Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016 Apr 9;387(10027):1540-50. Epub 2015 Dec 19. link to original article contains protocol PubMed
Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, Park K, Smith D, Artal-Cortes A, Lewanski C, Braiteh F, Waterkamp D, He P, Zou W, Chen DS, Yi J, Sandler A, Rittmeyer A; POPLAR Study Group. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016 Apr 30;387(10030):1837-46. Epub 2016 Mar 9. link to original article contains protocol PubMed

Docetaxel & Ramucirumab

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Regimen

Study	Evidence	Comparator	Efficacy
Garon et al. 2014 (REVEL)	Phase III	Docetaxel	Seems to have superior OS

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV once on day 1
- East Asian patients were later recommended to receive Docetaxel (Taxotere) 60 mg/m² IV once on day 1
Ramucirumab (Cyramza) 10 mg/kg IV once on day 1

Supportive medications

Colony-stimulating factors and erythroid-stimulating factor use per investigator discretion.

21-day cycles, given until progression of disease, unacceptable toxicity, withdrawal, or death

References

Garon EB, Ciuleanu TE, Arrieta O, Prabhash K, Syrigos KN, Goksel T, Park K, Gorbunova V, Kowalyszyn RD, Pikiel J, Czyzewicz G, Orlov SV, Lewanski CR, Thomas M, Bidoli P, Dakhil S, Gans S, Kim JH, Grigorescu A, Karaseva N, Reck M, Cappuzzo F, Alexandris E, Sashegyi A, Yurasov S, Pérol M. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014 Aug 23;384(9944):665-73. link to original article contains verified protocol PubMed

Erlotinib (Tarceva)

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Regimen #1

Study	Evidence	Comparator	Efficacy
Shepherd et al. 2005 (NCIC CTG BR.21)	Phase III	Placebo	Superior OS
Lilenbaum et al. 2008	Phase III	Carboplatin & Paclitaxel	Seems to have inferior OS
Zhou et al. 2011 (OPTIMAL, CTONG-0802)	Phase III	Carboplatin & Gemcitabine	Superior PFS
Scagliotti et al. 2014	Phase III	Erlotinib & Figitumumab	Seems not superior
Soria et al. 2015 (LUX-Lung 8)	Phase III	Afatinib	Seems to have inferior OS
Urata et al. 2016 (WJOG 5108L)	Phase III	Gefitinib	Inconclusive whether non-inferior

Chemotherapy

Erlotinib (Tarceva) 150 mg PO once per day

Continued until progression or intolerance

Regimen #2, low-dose

Study	Evidence
Yeo et al. 2010	Retrospective

Chemotherapy

Erlotinib (Tarceva) 25 mg PO once per day

Continued until progression or intolerance

References

Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):123-32. link to original article contains protocol PubMed
Lilenbaum R, Axelrod R, Thomas S, Dowlati A, Seigel L, Albert D, Witt K, Botkin D. Randomized phase II trial of erlotinib or standard chemotherapy in patients with advanced non-small-cell lung cancer and a performance status of 2. J Clin Oncol. 2008 Feb 20;26(6):863-9. link to original article contains protocol PubMed
Yeo WL, Riely GJ, Yeap BY, Lau MW, Warner JL, Bodio K, Huberman MS, Kris MG, Tenen DG, Pao W, Kobayashi S, Costa DB. Erlotinib at a dose of 25 mg daily for non-small cell lung cancers with EGFR mutations. J Thorac Oncol. 2010 Jul;5(7):1048-53. link to PMC article PubMed
Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011 Aug;12(8):735-42. Epub 2011 Jul 23. link to original article PubMed
1. Update: Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015 Sep;26(9):1877-83. Epub 2015 Jul 3. link to original article PubMed
Scagliotti GV, Bondarenko I, Blackhall F, Barlesi F, Hsia TC, Jassem J, Milanowski J, Popat S, Sanchez-Torres JM, Novello S, Benner RJ, Green S, Molpus K, Soria JC, Shepherd FA. Randomized, phase III trial of figitumumab in combination with erlotinib versus erlotinib alone in patients with nonadenocarcinoma nonsmall-cell lung cancer. Ann Oncol. 2015 Mar;26(3):497-504. Epub 2014 Nov 13. link to original article PubMed
Soria JC, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, Göker E, Georgoulias V, Li W, Isla D, Guclu SZ, Morabito A, Min YJ, Ardizzoni A, Gadgeel SM, Wang B, Chand VK, Goss GD; LUX-Lung 8 Investigators. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015 Aug;16(8):897-907. Epub 2015 Jul 5. link to original article contains protocol PubMed
Urata Y, Katakami N, Morita S, Kaji R, Yoshioka H, Seto T, Satouchi M, Iwamoto Y, Kanehara M, Fujimoto D, Ikeda N, Murakami H, Daga H, Oguri T, Goto I, Imamura F, Sugawara S, Saka H, Nogami N, Negoro S, Nakagawa K, Nakanishi Y. Randomized Phase III Study Comparing Gefitinib With Erlotinib in Patients With Previously Treated Advanced Lung Adenocarcinoma: WJOG 5108L. J Clin Oncol. 2016 Sep 20;34(27):3248-57. Epub 2016 Mar 28. link to original article contains verified protocol PubMed

Gefitinib (Iressa)

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Regimen

Study	Evidence	Comparator	Efficacy
Kris et al. 2003 (IDEAL2)	Randomized Phase II	Gefitinib 500 mg/day	Seems not superior
Kim et al. 2008 (INTEREST)	Phase III	Docetaxel	Seems non-inferior
Mok et al. 2009 (IPASS)	Phase III	Carboplatin & Paclitaxel	Superior PFS
Shi et al. 2013 (ICOGEN)	Phase III	Icotinib	Seems non-inferior
Douillard, et al. 2014	Phase IV
Park et al. 2016 (LUX-Lung 7)	Randomized Phase II	Afatinib	Seems to have inferior PFS
Urata et al. 2016 (WJOG 5108L)	Phase III	Erlotinib	Inconclusive whether non-inferior
Cheng et al. 2016	Randomized Phase II	P+G	Seems to have inferior PFS

Chemotherapy

Gefitinib (Iressa) 250 mg PO once per day

Given until progression of objective disease or unacceptable toxicity

References

Kris MG, Natale RB, Herbst RS, Lynch TJ Jr, Prager D, Belani CP, Schiller JH, Kelly K, Spiridonidis H, Sandler A, Albain KS, Cella D, Wolf MK, Averbuch SD, Ochs JJ, Kay AC. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA. 2003 Oct 22;290(16):2149-58. link to original article PubMed
Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Wu YL, Li LY, Watkins CL, Sellers MV, Lowe ES, Sun Y, Liao ML, Osterlind K, Reck M, Armour AA, Shepherd FA, Lippman SM, Douillard JY. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet. 2008 Nov 22;372(9652):1809-18. link to original article contains verified protocol PubMed
Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947-57. Epub 2009 Aug 19. link to original article contains verified protocol PubMed
Shi Y, Zhang L, Liu X, Zhou C, Zhang L, Zhang S, Wang D, Li Q, Qin S, Hu C, Zhang Y, Chen J, Cheng Y, Feng J, Zhang H, Song Y, Wu YL, Xu N, Zhou J, Luo R, Bai C, Jin Y, Liu W, Wei Z, Tan F, Wang Y, Ding L, Dai H, Jiao S, Wang J, Liang L, Zhang W, Sun Y. Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial. Lancet Oncol. 2013 Sep;14(10):953-61. Epub 2013 Aug 13. link to original article PubMed
Douillard JY, Ostoros G, Cobo M, Ciuleanu T, McCormack R, Webster A, Milenkova T. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br J Cancer. 2014 Jan 7;110(1):55-62. link to PMC article contains verified protocol PubMed
Park K, Tan EH, O'Byrne K, Zhang L, Boyer M, Mok T, Hirsh V, Yang JC, Lee KH, Lu S, Shi Y, Kim SW, Laskin J, Kim DW, Arvis CD, Kölbeck K, Laurie SA, Tsai CM, Shahidi M, Kim M, Massey D, Zazulina V, Paz-Ares L. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016 May;17(5):577-89. Epub 2016 Apr 12. link to original article contains protocol PubMed
Urata Y, Katakami N, Morita S, Kaji R, Yoshioka H, Seto T, Satouchi M, Iwamoto Y, Kanehara M, Fujimoto D, Ikeda N, Murakami H, Daga H, Oguri T, Goto I, Imamura F, Sugawara S, Saka H, Nogami N, Negoro S, Nakagawa K, Nakanishi Y. Randomized Phase III Study Comparing Gefitinib With Erlotinib in Patients With Previously Treated Advanced Lung Adenocarcinoma: WJOG 5108L. J Clin Oncol. 2016 Sep 20;34(27):3248-57. Epub 2016 Mar 28. link to original article contains verified protocol PubMed
Cheng Y, Murakami H, Yang PC, He J, Nakagawa K, Kang JH, Kim JH, Wang X, Enatsu S, Puri T, Orlando M, Yang JC. Randomized Phase II Trial of Gefitinib With and Without Pemetrexed as First-Line Therapy in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations. J Clin Oncol. 2016 Sep 20;34(27):3258-66. Epub 2016 Aug 9. link to original article contains verified protocol PubMed

Gemcitabine (Gemzar)

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Regimen #1

Study	Evidence	Comparator	Efficacy
Quoix et al. 2011 (IFCT-0501)	Phase III	Carboplatin & Paclitaxel	Inferior OS

Study involved only patients 70 to 89 years old

Chemotherapy

Gemcitabine (Gemzar) 1150 mg/m² IV once per day on days 1 & 8

Supportive medications

Growth factor support was not recommended as primary prophylaxis during cycle 1, but could be used if the patient develops grade 3 to 4 neutropenia

21-day cycle for up to 5 cycles

Regimen #2

Study	Evidence	Comparator	Efficacy
Sederholm et al. 2005	Phase III	Carboplatin & Gemcitabine	Seems to have inferior OS

Chemotherapy

Gemcitabine (Gemzar) 1250 mg/m² IV once per day on days 1 & 8

21-day cycles

Regimen #3

Study	Evidence	Comparator	Efficacy
Gridelli et al. 2003 (MILES)	Phase III	Gemcitabine & Vinorelbine	Seems not superior
Gridelli et al. 2003 (MILES)	Phase III	Vinorelbine	Seems not superior

Study involved only patients at least 70 years old

Chemotherapy

Gemcitabine (Gemzar) 1200 mg/m² IV once per day on days 1 & 8

Supportive medications

"Antiemetic agents and other supportive treatments were provided at the discretion of the treating physician."

21-day cycle for up to 6 cycles

References

Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, Barbera S, Ferraù F, Piazza E, Rosetti F, Clerici M, Bertetto O, Robbiati SF, Frontini L, Sacco C, Castiglione F, Favaretto A, Novello S, Migliorino MR, Gasparini G, Galetta D, Iaffaioli RV, Gebbia V; MILES Investigators. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst. 2003 Mar 5;95(5):362-72. link to original article contains verified protocol PubMed
Sederholm C, Hillerdal G, Lamberg K, Kölbeck K, Dufmats M, Westberg R, Gawande SR. Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group. J Clin Oncol. 2005 Nov 20;23(33):8380-8. link to original article contains verified protocol PubMed
Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, Dauba J, Debieuvre D, Souquet PJ, Bigay-Game L, Dansin E, Poudenx M, Molinier O, Vaylet F, Moro-Sibilot D, Herman D, Bennouna J, Tredaniel J, Ducoloné A, Lebitasy MP, Baudrin L, Laporte S, Milleron B; Intergroupe Francophone de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17;378(9796):1079-88. Epub 2011 Aug 8. link to original article contains verified protocol PubMed

Gemcitabine & Vinorelbine

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Regimen

Study	Evidence	Comparator	Efficacy
Gridelli et al. 2003 (MILES)	Phase III	Gemcitabine	Seems not superior
Gridelli et al. 2003 (MILES)	Phase III	Vinorelbine	Seems not superior

Study involved only patients at least 70 years old

Chemotherapy

Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1 & 8
Vinorelbine (Navelbine) 25 mg/m² IV once per day on days 1 & 8

Supportive medications

"Antiemetic agents and other supportive treatments were provided at the discretion of the treating physician."

21-day cycle for up to 6 cycles

References

Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, Barbera S, Ferraù F, Piazza E, Rosetti F, Clerici M, Bertetto O, Robbiati SF, Frontini L, Sacco C, Castiglione F, Favaretto A, Novello S, Migliorino MR, Gasparini G, Galetta D, Iaffaioli RV, Gebbia V; MILES Investigators. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst. 2003 Mar 5;95(5):362-72. link to original article contains verified protocol PubMed

Osimertinib (Tagrisso)

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Regimen

Study	Evidence	Comparator	Efficacy
Jänne et al. 2015 (AURA)	Phase I
AURA2 (ongoing)	Phase II
FLAURA (ongoing)	Phase III	Gefitinib (Iressa) & Erlotinib (Tarceva)	TBD

Chemotherapy

Osimertinib (Tagrisso) 80 mg PO once per day

Given until progression of disease or unacceptable toxicity

References

Non-peer-reviewed references are listed because of a lack of published peer-reviewed articles at the time of osimertinib's 11/13/2015 FDA approval.

Jänne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam SS, Ahn MJ, Kim SW, Su WC, Horn L, Haggstrom D, Felip E, Kim JH, Frewer P, Cantarini M, Brown KH, Dickinson PA, Ghiorghiu S, Ranson M. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med. 2015 Apr 30;372(18):1689-99. link to original article contains verified protocol PubMed
Osimertinib (Tagrisso) package insert
16th World Conference on Lung Cancer abstracts MINI16.06, MINI16.07, MINI16.08.
1. Yang J C-H, et al: World Conf on Lung Cancer. Abst MINI16.06. Sept 8, 2015.
2. Ramalingam S, et al: World Conf on Lung Cancer. Abst MINI16.07. Sept 8, 2015.
3. Mitsudomi T, et al: World Conf on Lung Cancer. Abst MINI16.08. Sept 8, 2015.
Phase II AZD9291 Open Label Study in NSCLC After Previous EGFR TKI Therapy in EGFR and T790M Mutation Positive Tumours (AURA2) (clinicaltrials.gov)
AZD9291 Versus Gefitinib or Erlotinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (FLAURA) (clinicaltrials.gov)
David Planchard, MD, PhD. AZD9291 a novel EGFR-TKI that overcomes T790M-mediated resistance in NSCLC. (PowerPoint presentation)

Nivolumab (Opdivo)

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Regimen

Study	Evidence	ORR	Comparator	Efficacy	Pt Population
Rizvi et al. 2015 (CheckMate 063)	Phase II	14% (95% CI 9 - 22)			Chemo exposed
Brahmer et al. 2015 (CheckMate 017)	Phase III	20% (95% CI 14 - 28)	Docetaxel	Superior OS	Squamous only, chemo exposed
Borghaei et al. 2015 (CheckMate 057)	Phase III	19% (95% CI 15 - 24)	Docetaxel	Superior OS	Non-squamous only, chemo exposed

Immunotherapy

Nivolumab (Opdivo) 3 mg/kg IV once on day 1
- Notably, on 9/13/16 the FDA recommended that dosing for this indication be changed to 240 mg with the same schedule based on updated pharmacokinetic data.

2-week cycles, given until progression of disease or unacceptable toxicity

References

Rizvi NA, Mazières J, Planchard D, Stinchcombe TE, Dy GK, Antonia SJ, Horn L, Lena H, Minenza E, Mennecier B, Otterson GA, Campos LT, Gandara DR, Levy BP, Nair SG, Zalcman G, Wolf J, Souquet PJ, Baldini E, Cappuzzo F, Chouaid C, Dowlati A, Sanborn R, Lopez-Chavez A, Grohe C, Huber RM, Harbison CT, Baudelet C, Lestini BJ, Ramalingam SS. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 2015 Feb 19. link to original article contains verified protocol PubMed
Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Arén Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. Epub 2015 May 31. link to original article PubMed
Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhäufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crinò L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Oct 22;373(17):1627-39. Epub 2015 Sep 27. link to original article PubMed

P+G

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P+G: Pemetrexed, Gefitinib

Regimen

Study	Evidence	Comparator	Efficacy
Cheng et al. 2016	Randomized Phase II	Gefitinib	Seems to have superior PFS

Chemotherapy

Pemetrexed (Alimta) 500 mg IV once on day 1
Gefitinib (Iressa) 250 mg PO once per day

3-week cycles, given until progression of objective disease or unacceptable toxicity

References

Cheng Y, Murakami H, Yang PC, He J, Nakagawa K, Kang JH, Kim JH, Wang X, Enatsu S, Puri T, Orlando M, Yang JC. Randomized Phase II Trial of Gefitinib With and Without Pemetrexed as First-Line Therapy in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations. J Clin Oncol. 2016 Sep 20;34(27):3258-66. Epub 2016 Aug 9. link to original article contains verified protocol PubMed

Pembrolizumab (Keytruda)

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Regimen

Study	Evidence	ORR	Comparator	Efficacy	Pt Population
Herbst et al. 2015 (KEYNOTE-010)	Phase II/III	2 mg/kg: 18% (95% CI 14 - 23) 10 mg/kg: 19% (95% CI 15 - 23)	Docetaxel	Superior OS	Chemo exposed

Immunotherapy

Pembrolizumab (Keytruda) 2 mg/kg or 10 mg/kg IV once on day 1

21-day cycles, given until progression of disease or unacceptable toxicity

References

Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn MJ, Felip E, Lee JS, Hellmann MD, Hamid O, Goldman JW, Soria JC, Dolled-Filhart M, Rutledge RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator K, Gandhi L; KEYNOTE-001 Investigators. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015 May 21;372(21):2018-28. Epub 2015 Apr 19. link to original article PubMed
Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016 Apr 9;387(10027):1540-50. Epub 2015 Dec 19. link to original article contains protocol PubMed

Pemetrexed (Alimta)

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Example orders

Example orders for Pemetrexed (Alimta) in non-small cell lung cancer

Regimen

Study	Evidence	Comparator	Efficacy
Hanna et al. 2004	Phase III	Docetaxel	Inconclusive whether non-inferior
Ardizzoni et al. 2012 (GOIRC 02-2006)	Randomized Phase II	Carboplatin & Pemetrexed	Seems not superior
Shaw et al. 2013	Phase III	Crizotinib	Inferior PFS
Zukin et al. 2013	Phase III	Carboplatin & Pemetrexed	Inferior OS

Chemotherapy

Pemetrexed (Alimta) 500 mg/m² IV over 10 minutes once on day 1

Supportive medications

(per Ardizzoni et al. 2012):
Dexamethasone (Decadron) 4 mg or equivalent corticosteroid PO BID on the day before, the day of, and day after each dose of pemetrexed
Folic acid 350 to 600 mcg PO once per day, starting 1 to 2 weeks before the first dose of pemetrexed, to be taken throughout pemetrexed therapy.
- Hanna et al. 2004 used folic acid 1 mg PO once per day
Cyanocobalamin (Vitamin B12) 1000 mcg IM once every 9 weeks, first dose 1 to 2 weeks before the first dose of pemetrexed, to be given throughout pemetrexed therapy

21-day cycles

Ardizzoni et al. 2012 & Zukin et al. 2013 treated patients for up to 4 cycles or until progressive disease, unacceptable toxicity, or patient refusal.

References

Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, Gatzemeier U, Tsao TC, Pless M, Muller T, Lim HL, Desch C, Szondy K, Gervais R, Shaharyar, Manegold C, Paul S, Paoletti P, Einhorn L, Bunn PA Jr. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004 May 1;22(9):1589-97. link to original article contains protocol PubMed
Ardizzoni A, Tiseo M, Boni L, Vincent AD, Passalacqua R, Buti S, Amoroso D, Camerini A, Labianca R, Genestreti G, Boni C, Ciuffreda L, Di Costanzo F, de Marinis F, Crinò L, Santo A, Pazzola A, Barbieri F, Zilembo N, Colantonio I, Tibaldi C, Mattioli R, Cafferata MA, Camisa R, Smit EF. Pemetrexed versus pemetrexed and carboplatin as second-line chemotherapy in advanced non-small-cell lung cancer: results of the GOIRC 02-2006 randomized phase II study and pooled analysis with the NVALT7 trial. J Clin Oncol. 2012 Dec 20;30(36):4501-7. Epub 2012 Oct 29. link to original article contains verified protocol PubMed
Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O'Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Jänne PA. Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer. N Engl J Med. 2013 Jun 20;368(25):2385-94. Epub 2013 Jun 1. link to original article link to supplementary appendix contains verified protocol PubMed
Zukin M, Barrios CH, Rodrigues Pereira J, De Albuquerque Ribeiro R, de Mendonça Beato CA, do Nascimento YN, Murad A, Franke FA, Precivale M, de Lima Araujo LH, Da Rocha Baldotto CS, Vieira FM, Small IA, Ferreira CG, Lilenbaum RC. Randomized Phase III Trial of Single-Agent Pemetrexed Versus Carboplatin and Pemetrexed in Patients With Advanced Non-Small-Cell Lung Cancer and Eastern Cooperative Oncology Group Performance Status of 2. J Clin Oncol. 2013 Aug 10;31(23):2849-53. Epub 2013 Jun 17. link to original article contains verified protocol PubMed

Placebo (Observation)

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Regimen

Study	Evidence	Comparator	Efficacy
Elderly Lung Cancer Vinorelbine Italian Study Group, 1999	Phase III	Vinorelbine	Seems to have inferior OS
Shepherd et al. 2005 (NCIC CTG BR.21)	Phase III	Erlotinib	Inferior OS
Miller et al. 2012 (LUX-Lung 1)	Phase III	Afatinib	Inferior PFS

No active antineoplastic treatment. Placed here because one or more randomized clinical trials included a placebo or observation arm in this disease context.

References

The Elderly Lung Cancer Vinorelbine Italian Study Group. Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. J Natl Cancer Inst. 1999 Jan 6;91(1):66-72. link to original article contains verified protocol PubMed
Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):123-32. link to original article contains protocol PubMed
Miller VA, Hirsh V, Cadranel J, Chen YM, Park K, Kim SW, Zhou C, Su WC, Wang M, Sun Y, Heo DS, Crino L, Tan EH, Chao TY, Shahidi M, Cong XJ, Lorence RM, Yang JC. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol. 2012 May;13(5):528-38. Epub 2012 Mar 26. link to original article contains verified protocol PubMed

Vinorelbine (Navelbine)

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Regimen #1

Study	Evidence	Comparator	Efficacy
Quoix et al. 2011 (IFCT-0501)	Phase III	Carboplatin & Paclitaxel	Inferior OS

Study involved only patients 70 to 89 years old

Chemotherapy

Vinorelbine (Navelbine) 25 mg/m² IV once per day on days 1 & 8

Supportive medications

Growth factor support was not recommended as primary prophylaxis during cycle 1, but could be used if the patient develops grade 3 to 4 neutropenia

21-day cycle for up to 5 cycles

Regimen #2

Study	Evidence	Comparator	Efficacy
Elderly Lung Cancer Vinorelbine Italian Study Group, 1999	Phase III	Supportive care	Seems to have superior OS
Gridelli et al. 2003 (MILES)	Phase III	Gemcitabine	Seems not superior
Gridelli et al. 2003 (MILES)	Phase III	Gemcitabine & Vinorelbine	Seems not superior

Study involved only patients at least 70 years old

Chemotherapy

Vinorelbine (Navelbine) 30 mg/m² IV once per day on days 1 & 8

Supportive medications

(varies depending on reference):
Elderly Lung Cancer Vinorelbine Italian Study Group, 1999: Metoclopramide (Reglan) 20 mg IV bolus prior to Vinorelbine (Navelbine)
Gridelli et al. 2003: "Antiemetic agents and other supportive treatments were provided at the discretion of the treating physician."

21-day cycle for up to 6 cycles

Regimen #3

Study	Evidence	Comparator	Efficacy
Jassem et al. 2001	Randomized Phase II	Oral vinorelbine	Seems not superior

Chemotherapy

Vinorelbine (Navelbine) 30 mg/m² IV over 5 to 10 minutes once per week

Supportive medications

Patients who had either grade 4 neutropenia lasting at least 5 days or both fever and grade 3 or 4 neutropenia could receive G-CSF (dose/schedule/duration not specified)
Metoclopramide (Reglan) (dose/schedule/route not specified) used first for nausea
Nausea despite metoclopramide was treated with a 5-HT3 antagonist such as Ondansetron (Zofran) or Granisetron (Kytril) (dose/schedule/route not specified) prn nausea

Continued until progression

Regimen #4

Study	Evidence	Comparator	Efficacy
Jassem et al. 2001	Randomized Phase II	Intravenous vinorelbine	Seems not superior

Chemotherapy

Vinorelbine (Navelbine) 60 mg/m² PO once per week, increased to 80 mg/m² PO once per week with 4th dose, if no severe neutropenia

Supportive medications

Patients who had either grade 4 neutropenia lasting at least 5 days or both fever and grade 3 or 4 neutropenia could receive G-CSF (dose/schedule/duration not specified)
Metoclopramide (Reglan) (dose/schedule/route not specified) used first for nausea
Nausea despite metoclopramide was treated with a 5-HT3 antagonist such as Ondansetron (Zofran) or Granisetron (Kytril) (dose/schedule/route not specified) prn nausea

Continued until progression

References

The Elderly Lung Cancer Vinorelbine Italian Study Group. Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. J Natl Cancer Inst. 1999 Jan 6;91(1):66-72. link to original article contains verified protocol PubMed
Jassem J, Ramlau R, Karnicka-Mlodkowska H, Krawczyk K, Krzakowski M, Zatloukal P, Lemarié E, Hartmann W, Novakova L, O'Brien M, Depierr A. A multicenter randomized phase II study of oral vs. intravenous vinorelbine in advanced non-small-cell lung cancer patients. Ann Oncol. 2001 Oct;12(10):1375-81. link to original article contains verified protocol PubMed
Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, Barbera S, Ferraù F, Piazza E, Rosetti F, Clerici M, Bertetto O, Robbiati SF, Frontini L, Sacco C, Castiglione F, Favaretto A, Novello S, Migliorino MR, Gasparini G, Galetta D, Iaffaioli RV, Gebbia V; MILES Investigators. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst. 2003 Mar 5;95(5):362-72. link to original article contains verified protocol PubMed
Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, Dauba J, Debieuvre D, Souquet PJ, Bigay-Game L, Dansin E, Poudenx M, Molinier O, Vaylet F, Moro-Sibilot D, Herman D, Bennouna J, Tredaniel J, Ducoloné A, Lebitasy MP, Baudrin L, Laporte S, Milleron B; Intergroupe Francophone de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17;378(9796):1079-88. Epub 2011 Aug 8. link to original article contains verified protocol PubMed

Maintenance

Bevacizumab (Avastin)

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Regimen #1

Study	Evidence	Comparator	Efficacy
Barlesi et al. 2013 (AVAPERL (MO22089))	Phase III	Bevacizumab & Pemetrexed maintenance	Inferior PFS

Treatment preceded by cisplatin, pemetrexed, bevacizumab x 4.

Chemotherapy

Bevacizumab (Avastin) 7.5 mg/kg IV once on day 1

21-day cycles, given until progression of disease or unacceptable toxicity

Regimen #2

Study	Evidence
Sandler et al. 2006 (ECOG 4599)	Non-randomized portion of RCT
Patel et al. 2013 (PointBreak)	Non-randomized portion of RCT

Treatment in ECOG 4599 preceded by PacCBev x 6. Treatment in PointBreak preceded by PacCBev x 4.

Chemotherapy

Bevacizumab (Avastin) 15 mg/kg IV once on day 1

21-day cycles, given until progression of disease or unacceptable toxicity

References

Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14;355(24):2542-50. link to original article contains verified protocol PubMed
1. Subset analysis: Ramalingam SS, Dahlberg SE, Langer CJ, Gray R, Belani CP, Brahmer JR, Sandler AB, Schiller JH, Johnson DH; Eastern Cooperative Oncology Group. Outcomes for elderly, advanced-stage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol. 2008 Jan 1;26(1):60-5. link to original article contains verified protocol PubMed
Barlesi F, Scherpereel A, Rittmeyer A, Pazzola A, Ferrer Tur N, Kim JH, Ahn MJ, Aerts JG, Gorbunova V, Vikström A, Wong EK, Perez-Moreno P, Mitchell L, Groen HJ. Randomized Phase III Trial of Maintenance Bevacizumab With or Without Pemetrexed After First-Line Induction With Bevacizumab, Cisplatin, and Pemetrexed in Advanced Nonsquamous Non-Small-Cell Lung Cancer: AVAPERL (MO22089). J Clin Oncol. 2013 Aug 20;31(24):3004-11. Epub 2013 Jul 8. link to original article contains verified protocol PubMed
Patel JD, Socinski MA, Garon EB, Reynolds CH, Spigel DR, Olsen MR, Hermann RC, Jotte RM, Beck T, Richards DA, Guba SC, Liu J, Frimodt-Moller B, John WJ, Obasaju CK, Pennella EJ, Bonomi P, Govindan R. PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. J Clin Oncol. 2013 Dec 1;31(34):4349-57. link to original article contains verified protocol PubMed

Bevacizumab & Pemetrexed

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Regimen #1

Study	Evidence	Comparator	Efficacy
Barlesi et al. 2013 (AVAPERL (MO22089))	Phase III	Bevacizumab maintenance	Superior PFS

Treatment preceded by cisplatin, pemetrexed, bevacizumab x 4.

Chemotherapy

Bevacizumab (Avastin) 7.5 mg/kg IV once on day 1
Pemetrexed (Alimta) 500 mg/m² IV over 10 minutes once on day 1

Supportive medications

Cyanocobalamin (Vitamin B12) 1000 mcg IM every 3 cycles (i.e. every 9 weeks), given throughout therapy
Folic acid 350 to 1000 mcg PO once per day, given throughout therapy
Dexamethasone (Decadron) 4 mg PO BID on days -1, 1, 2 of each cycle

21-day cycles, given until progression of disease or unacceptable toxicity

Regimen #2

Study	Evidence
Patel et al. 2013 (PointBreak)	Non-randomized portion of RCT

Treatment preceded by PemCBev x 4.

Chemotherapy

Bevacizumab (Avastin) 15 mg/kg IV once on day 1
Pemetrexed (Alimta) 500 mg/m² IV once on day 1

Supportive medications

Premedications, folic acid, and vitamin supplementation per pemetrexed label
Erythropoietic agents or granulocyte colony-stimulating factors allowed per ASCO & NCCN guidelines

21-day cycles, given until progression of disease or unacceptable toxicity

References

Barlesi F, Scherpereel A, Rittmeyer A, Pazzola A, Ferrer Tur N, Kim JH, Ahn MJ, Aerts JG, Gorbunova V, Vikström A, Wong EK, Perez-Moreno P, Mitchell L, Groen HJ. Randomized Phase III Trial of Maintenance Bevacizumab With or Without Pemetrexed After First-Line Induction With Bevacizumab, Cisplatin, and Pemetrexed in Advanced Nonsquamous Non-Small-Cell Lung Cancer: AVAPERL (MO22089). J Clin Oncol. 2013 Aug 20;31(24):3004-11. Epub 2013 Jul 8. link to original article contains verified protocol PubMed
Patel JD, Socinski MA, Garon EB, Reynolds CH, Spigel DR, Olsen MR, Hermann RC, Jotte RM, Beck T, Richards DA, Guba SC, Liu J, Frimodt-Moller B, John WJ, Obasaju CK, Pennella EJ, Bonomi P, Govindan R. PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. J Clin Oncol. 2013 Dec 1;31(34):4349-57. link to original article contains verified protocol PubMed

Ipilimumab (Yervoy)

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Regimen

Study	Evidence
Lynch et al. 2012	Non-randomized portion of RCT

Treatment preceded by carboplatin, paclitaxel, ipilimumab x 6.

Immunotherapy

Ipilimumab (Yervoy) 10 mg/kg IV once on day 1

12-week cycles, given until progression of disease or unacceptable toxicity

References

Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012 Jun 10;30(17):2046-54. Epub 2012 Apr 30. link to original article contains verified protocol PubMed

Necitumumab (Portrazza)

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Regimen

Study	Evidence
Thatcher et al. 2015 (SQUIRE)	Non-randomized portion of RCT

Patients had stage IV squamous non-small-cell lung cancer; treatment preceded by Cisplatin, Gemcitabine, Necitumumab x 6.

Chemotherapy

Necitumumab (Portrazza) 800 mg IV over at least 50 minutes once per day on days 1 & 8

21-day cycles, given until progression of disease or unacceptable toxicity

References

Thatcher N, Hirsch FR, Luft AV, Szczesna A, Ciuleanu TE, Dediu M, Ramlau R, Galiulin RK, Bálint B, Losonczy G, Kazarnowicz A, Park K, Schumann C, Reck M, Depenbrock H, Nanda S, Kruljac-Letunic A, Kurek R, Paz-Ares L, Socinski MA; SQUIRE Investigators. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2015 Jul;16(7):763-74. link to original article contains verified protocol PubMed

Pemetrexed (Alimta)

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Example orders

Example orders for Pemetrexed (Alimta) in non-small cell lung cancer

Regimen

Study	Evidence	Comparator	Efficacy
Paz-Ares et al. 2012 (PARAMOUNT)	Phase III	Placebo	Superior PFS

Treatment preceded by 4 cycles of induction therapy with cisplatin & pemetrexed. Maintenance therapy started 21 to 42 days after cycle 4 day 1 of induction chemotherapy.

Chemotherapy

Pemetrexed (Alimta) 500 mg/m² IV once on day 1

Supportive medications

Folic acid, Cyanocobalamin (Vitamin B12), prophylactic Dexamethasone (Decadron)
"Investigators followed current American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) guidelines for use of colony-stimulating factors and erythropoiesis-stimulating agents."

21-day cycles, given until progression of disease, unacceptable toxicity, or physician/patient choice

References

Paz-Ares L, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2012 Mar;13(3):247-55. Epub 2012 Feb 16. link to original article contains verified protocol PubMed
1. Update: Paz-Ares LG, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. PARAMOUNT: Final Overall Survival Results of the Phase III Study of Maintenance Pemetrexed Versus Placebo Immediately After Induction Treatment With Pemetrexed Plus Cisplatin for Advanced Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2013 Aug 10;31(23):2895-902. Epub 2013 Jul 8. link to original article contains verified protocol PubMed

Placebo (Observation)

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Regimen

Study	Evidence	Comparator	Efficacy
Paz-Ares et al. 2012 (PARAMOUNT)	Phase III	Pemetrexed	Inferior PFS

Preceded by 4 cycles of induction therapy with cisplatin & pemetrexed. No further active treatment.

References

Paz-Ares L, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2012 Mar;13(3):247-55. Epub 2012 Feb 16. link to original article contains verified protocol PubMed
1. Update: Paz-Ares LG, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. PARAMOUNT: Final Overall Survival Results of the Phase III Study of Maintenance Pemetrexed Versus Placebo Immediately After Induction Treatment With Pemetrexed Plus Cisplatin for Advanced Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2013 Aug 10;31(23):2895-902. Epub 2013 Jul 8. link to original article contains verified protocol PubMed

@@ Line 21: / Line 21: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jco.ascopubs.org/content/26/31/5043.long Strauss et al. 2008 (CALGB 9633)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Placebo_.28Observation.29|Observation]]
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
@@ Line 39: / Line 36: @@
 ===References===
-# Strauss GM, Herndon JE 2nd, Maddaus MA, Johnstone DW, Johnson EA, Harpole DH, Gillenwater HH, Watson DM, Sugarbaker DJ, Schilsky RL, Vokes EE, Green MR. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol. 2008 Nov 1;26(31):5043-51. Epub 2008 Sep 22. [http://jco.ascopubs.org/content/26/31/5043.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18809614 PubMed]
+<!-- Presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, June 5-8, 2004, New Orleans, LA, and at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA. -->
+# Strauss GM, Herndon JE 2nd, Maddaus MA, Johnstone DW, Johnson EA, Harpole DH, Gillenwater HH, Watson DM, Sugarbaker DJ, Schilsky RL, Vokes EE, Green MR. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol. 2008 Nov 1;26(31):5043-51. Epub 2008 Sep 22. [http://jco.ascopubs.org/content/26/31/5043.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18809614 PubMed]
 ==Cisplatin & Docetaxel {{#subobject:211cca|Regimen=1}}==
@@ Line 54: / Line 52: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://icvts.oxfordjournals.org/content/20/6/783.long Barlesi et al. 2015]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine|Cisplatin & Gemcitabine]]
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
@@ Line 74: / Line 69: @@
 ===References===
-# Barlesi F, Chouaid C, Crequit J, Le Caer H, Pujol JL, Legodec J, Vergnenegre A, Le Treut J, Fabre-Guillevin E, Loundou A, Auquier P, Simeoni MC, Thomas PA. A randomized trial comparing adjuvant chemotherapy with gemcitabine plus cisplatin with docetaxel plus cisplatin in patients with completely resected non-small-cell lung cancer with quality of life as the primary objective. Interact Cardiovasc Thorac Surg. 2015 Jun;20(6):783-90. Epub 2015 Mar 11. [http://icvts.oxfordjournals.org/content/20/6/783.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/25765952 PubMed]
+# Barlesi F, Chouaid C, Crequit J, Le Caer H, Pujol JL, Legodec J, Vergnenegre A, Le Treut J, Fabre-Guillevin E, Loundou A, Auquier P, Simeoni MC, Thomas PA. A randomized trial comparing adjuvant chemotherapy with gemcitabine plus cisplatin with docetaxel plus cisplatin in patients with completely resected non-small-cell lung cancer with quality of life as the primary objective. Interact Cardiovasc Thorac Surg. 2015 Jun;20(6):783-90. Epub 2015 Mar 11. [http://icvts.oxfordjournals.org/content/20/6/783.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25765952 PubMed]
 ==Cisplatin & Etoposide {{#subobject:dbad67|Regimen=1}}==
@@ Line 86: / Line 81: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa031644 Arriagada et al. 2004]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
+|[[Non-small_cell_lung_cancer#Placebo_.28Observation.29|Observation]]
-padding:3px 6px 3px 6px;
+|style="background-color:#00cd00"|Seems to have superior OS
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Non-small_cell_lung_cancer#Cisplatin_.26_Vinblastine|Cisplatin & Vinblastine]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Vindesine|Cisplatin & Vindesine]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Vinorelbine|Cisplatin & Vinorelbine]]<br> [[Non-small_cell_lung_cancer#Placebo_.28Observation.29|Observation]]
 |-
 |}
@@ Line 104: / Line 96: @@
 ===References===
-# Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. [http://www.nejm.org/doi/full/10.1056/NEJMoa031644 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/14736927 PubMed]
+# Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. [http://www.nejm.org/doi/full/10.1056/NEJMoa031644 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14736927 PubMed]
 ==Cisplatin & Gemcitabine {{#subobject:289ea6|Regimen=1}}==
@@ Line 116: / Line 108: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://icvts.oxfordjournals.org/content/20/6/783.long Barlesi et al. 2015]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Cisplatin_.26_Docetaxel|Cisplatin & Docetaxel]]
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
@@ Line 136: / Line 125: @@
 ===References===
-# Barlesi F, Chouaid C, Crequit J, Le Caer H, Pujol JL, Legodec J, Vergnenegre A, Le Treut J, Fabre-Guillevin E, Loundou A, Auquier P, Simeoni MC, Thomas PA. A randomized trial comparing adjuvant chemotherapy with gemcitabine plus cisplatin with docetaxel plus cisplatin in patients with completely resected non-small-cell lung cancer with quality of life as the primary objective. Interact Cardiovasc Thorac Surg. 2015 Jun;20(6):783-90. Epub 2015 Mar 11. [http://icvts.oxfordjournals.org/content/20/6/783.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/25765952 PubMed]
+# Barlesi F, Chouaid C, Crequit J, Le Caer H, Pujol JL, Legodec J, Vergnenegre A, Le Treut J, Fabre-Guillevin E, Loundou A, Auquier P, Simeoni MC, Thomas PA. A randomized trial comparing adjuvant chemotherapy with gemcitabine plus cisplatin with docetaxel plus cisplatin in patients with completely resected non-small-cell lung cancer with quality of life as the primary objective. Interact Cardiovasc Thorac Surg. 2015 Jun;20(6):783-90. Epub 2015 Mar 11. [http://icvts.oxfordjournals.org/content/20/6/783.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25765952 PubMed]
 ==Cisplatin & Pemetrexed {{#subobject:1caad6|Regimen=1}}==
@@ Line 148: / Line 137: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://annonc.oxfordjournals.org/content/24/4/986.long Kreuter et al. 2013 (TREAT)]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
 |[[Non-small_cell_lung_cancer#Cisplatin_.26_Vinorelbine|Cisplatin & Vinorelbine]]
+|style="background-color:#00cd00"|Superior clinical feasibility rate
 |-
 |}
@@ Line 168: / Line 154: @@
 ===References===
-# Kreuter M, Vansteenkiste J, Fischer JR, Eberhardt W, Zabeck H, Kollmeier J, Serke M, Frickhofen N, Reck M, Engel-Riedel W, Neumann S, Thomeer M, Schumann C, De Leyn P, Graeter T, Stamatis G, Zuna I, Griesinger F, Thomas M; TREAT investigators. Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study. Ann Oncol. 2013 Apr;24(4):986-92. Epub 2012 Nov 15. [http://annonc.oxfordjournals.org/content/24/4/986.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23161898 PubMed]
+# Kreuter M, Vansteenkiste J, Fischer JR, Eberhardt W, Zabeck H, Kollmeier J, Serke M, Frickhofen N, Reck M, Engel-Riedel W, Neumann S, Thomeer M, Schumann C, De Leyn P, Graeter T, Stamatis G, Zuna I, Griesinger F, Thomas M; TREAT investigators. Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study. Ann Oncol. 2013 Apr;24(4):986-92. Epub 2012 Nov 15. [http://annonc.oxfordjournals.org/content/24/4/986.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23161898 PubMed]
 ==Cisplatin & Vinblastine {{#subobject:af5cc1|Regimen=1}}==
@@ Line 180: / Line 166: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa031644 Arriagada et al. 2004]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
+|[[Non-small_cell_lung_cancer#Placebo_.28Observation.29|Observation]]
-padding:3px 6px 3px 6px;
+|style="background-color:#00cd00"|Seems to have superior OS
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Non-small_cell_lung_cancer#Cisplatin_.26_Etoposide|Cisplatin & Etoposide]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Vindesine|Cisplatin & Vindesine]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Vinorelbine|Cisplatin & Vinorelbine]]<br> [[Non-small_cell_lung_cancer#Placebo_.28Observation.29|Observation]]
 |-
 |}
 ''Note: Exact days for parts of the regimen were not specified by Arriagada et al. 2004. This vinblastine schedule is extrapolated from regimen information in Table 1 in which vinblastine is said to be given "weekly from days 1 to 29" and "then every 2 weeks after day 43 until last cisplatin administration.''
 ====Chemotherapy====
@@ Line 200: / Line 182: @@
 ===References===
-# Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. [http://www.nejm.org/doi/full/10.1056/NEJMoa031644 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14736927 PubMed]
+# Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. [http://www.nejm.org/doi/full/10.1056/NEJMoa031644 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14736927 PubMed]
 ==Cisplatin & Vindesine {{#subobject:80fe2|Regimen=1}}==
@@ Line 212: / Line 194: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa031644 Arriagada et al. 2004]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
+|[[Non-small_cell_lung_cancer#Placebo_.28Observation.29|Observation]]
-padding:3px 6px 3px 6px;
+|style="background-color:#00cd00"|Seems to have superior OS
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Non-small_cell_lung_cancer#Cisplatin_.26_Etoposide|Cisplatin & Etoposide]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Vinblastine|Cisplatin & Vinblastine]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Vinorelbine|Cisplatin & Vinorelbine]]<br> [[Non-small_cell_lung_cancer#Placebo_.28Observation.29|Observation]]
 |-
 |}
@@ Line 232: / Line 211: @@
 ===References===
-# Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. [http://www.nejm.org/doi/full/10.1056/NEJMoa031644 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/14736927 PubMed]
+# Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. [http://www.nejm.org/doi/full/10.1056/NEJMoa031644 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14736927 PubMed]
 ==Cisplatin & Vinorelbine {{#subobject:ab1b88|Regimen=1}}==
@@ Line 244: / Line 223: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa043623 Winton et al. 2005 (JBR.10)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Placebo_.28Observation.29|Observation]]
+|style="background-color:#00cd00"|Seems to have superior OS
 |-
 |[http://annonc.oxfordjournals.org/content/24/4/986.long Kreuter et al. 2013 (TREAT)]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
 |[[Non-small_cell_lung_cancer#Cisplatin_.26_Pemetrexed|Cisplatin & Pemetrexed]]
+|style="background-color:#ff0000"|Inferior clinical feasibility rate
 |-
 |}
@@ Line 277: / Line 249: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa031644 Arriagada et al. 2004]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
+|[[Non-small_cell_lung_cancer#Placebo_.28Observation.29|Observation]]
-padding:3px 6px 3px 6px;
+|style="background-color:#00cd00"|Seems to have superior OS
-border-color:black;
+|-
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Non-small_cell_lung_cancer#Cisplatin_.26_Etoposide|Cisplatin & Etoposide]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Vinblastine|Cisplatin & Vinblastine]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Vindesine|Cisplatin & Vindesine]]<br> [[Non-small_cell_lung_cancer#Placebo_.28Observation.29|Observation]]
-|-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(06)70804-X/fulltext Douillard et al. 2006 (ANITA)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Placebo_.28Observation.29|Observation]]
+|style="background-color:#00cd00"|Seems to have superior OS
 |-
 |}
@@ Line 309: / Line 274: @@
 |-
 |[http://jjco.oxfordjournals.org/content/31/12/596.full Hotta et al. 2001]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 324: / Line 284: @@
 ===References===
-# Hotta K, Sekine I, Tamura T, Sawada M, Watanabe H, Kusaba H, Akiyama Y, Inoue A, Shimoyama T, Nokihara H, Ueda Y, Yamamoto N, Kunitoh H, Ohe Y, Kodama T, Saijo N. A phase I/II study of cisplatin and vinorelbine chemotherapy in patients with advanced non-small cell lung cancer. Jpn J Clin Oncol. 2001 Dec;31(12):596-600. [http://jjco.oxfordjournals.org/content/31/12/596.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11902490 PubMed]
+# Hotta K, Sekine I, Tamura T, Sawada M, Watanabe H, Kusaba H, Akiyama Y, Inoue A, Shimoyama T, Nokihara H, Ueda Y, Yamamoto N, Kunitoh H, Ohe Y, Kodama T, Saijo N. A phase I/II study of cisplatin and vinorelbine chemotherapy in patients with advanced non-small cell lung cancer. Jpn J Clin Oncol. 2001 Dec;31(12):596-600. [http://jjco.oxfordjournals.org/content/31/12/596.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11902490 PubMed]
-# Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. [http://www.nejm.org/doi/full/10.1056/NEJMoa031644 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/14736927 PubMed] content property of [http://hemonc.org HemOnc.org]
+# Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. [http://www.nejm.org/doi/full/10.1056/NEJMoa031644 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14736927 PubMed] content property of [http://hemonc.org HemOnc.org]
-# Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, Cormier Y, Goss G, Inculet R, Vallieres E, Fry W, Bethune D, Ayoub J, Ding K, Seymour L, Graham B, Tsao MS, Gandara D, Kesler K, Demmy T, Shepherd F; National Cancer Institute of Canada Clinical Trials Group; National Cancer Institute of the United States Intergroup JBR.10 Trial Investigators. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med. 2005 Jun 23;352(25):2589-97. [http://www.nejm.org/doi/full/10.1056/NEJMoa043623 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/15972865 PubMed]
+# Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, Cormier Y, Goss G, Inculet R, Vallieres E, Fry W, Bethune D, Ayoub J, Ding K, Seymour L, Graham B, Tsao MS, Gandara D, Kesler K, Demmy T, Shepherd F; National Cancer Institute of Canada Clinical Trials Group; National Cancer Institute of the United States Intergroup JBR.10 Trial Investigators. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med. 2005 Jun 23;352(25):2589-97. [http://www.nejm.org/doi/full/10.1056/NEJMoa043623 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15972865 PubMed]
-# Douillard JY, Rosell R, De Lena M, Carpagnano F, Ramlau R, Gonzáles-Larriba JL, Grodzki T, Pereira JR, Le Groumellec A, Lorusso V, Clary C, Torres AJ, Dahabreh J, Souquet PJ, Astudillo J, Fournel P, Artal-Cortes A, Jassem J, Koubkova L, His P, Riggi M, Hurteloup P. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol. 2006 Sep;7(9):719-27. [http://linkinghub.elsevier.com/retrieve/pii/S1470-2045%2806%2970804-X link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/16945766 PubMed]
+# Douillard JY, Rosell R, De Lena M, Carpagnano F, Ramlau R, Gonzáles-Larriba JL, Grodzki T, Pereira JR, Le Groumellec A, Lorusso V, Clary C, Torres AJ, Dahabreh J, Souquet PJ, Astudillo J, Fournel P, Artal-Cortes A, Jassem J, Koubkova L, His P, Riggi M, Hurteloup P. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol. 2006 Sep;7(9):719-27. [http://linkinghub.elsevier.com/retrieve/pii/S1470-2045%2806%2970804-X link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16945766 PubMed]
-# Kreuter M, Vansteenkiste J, Fischer JR, Eberhardt W, Zabeck H, Kollmeier J, Serke M, Frickhofen N, Reck M, Engel-Riedel W, Neumann S, Thomeer M, Schumann C, De Leyn P, Graeter T, Stamatis G, Zuna I, Griesinger F, Thomas M; TREAT investigators. Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study. Ann Oncol. 2013 Apr;24(4):986-92. Epub 2012 Nov 15. [http://annonc.oxfordjournals.org/content/24/4/986.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23161898 PubMed]
+# Kreuter M, Vansteenkiste J, Fischer JR, Eberhardt W, Zabeck H, Kollmeier J, Serke M, Frickhofen N, Reck M, Engel-Riedel W, Neumann S, Thomeer M, Schumann C, De Leyn P, Graeter T, Stamatis G, Zuna I, Griesinger F, Thomas M; TREAT investigators. Randomized phase 2 trial on refinement of early-stage NSCLC adjuvant chemotherapy with cisplatin and pemetrexed versus cisplatin and vinorelbine: the TREAT study. Ann Oncol. 2013 Apr;24(4):986-92. Epub 2012 Nov 15. [http://annonc.oxfordjournals.org/content/24/4/986.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23161898 PubMed]
-==Placebo (Observation) {{#subobject:3fd960|Regimen=1}}==
+==Placebo (Observation)==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
@@ Line 336: / Line 296: @@
 |}
-===Regimen {{#subobject:9ada39|Variant=1}}===
+===Regimen===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|rowspan=4|[http://www.nejm.org/doi/full/10.1056/NEJMoa031644 Arriagada et al. 2004]
+|rowspan=4 style="background-color:#00cd00"|Phase III
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Etoposide|Cisplatin & Etoposide]]
+|style="background-color:#ff0000"|Seems to have inferior OS
+|-
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Vinblastine|Cisplatin & Vinblastine]]
+|style="background-color:#ff0000"|Seems to have inferior OS
+|-
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Vindesine|Cisplatin & Vindesine]]
+|style="background-color:#ff0000"|Seems to have inferior OS
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa031644 Arriagada et al. 2004]
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Vinorelbine|Cisplatin & Vinorelbine]]
-|<span
+|style="background-color:#ff0000"|Seems to have inferior OS
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Non-small_cell_lung_cancer#Cisplatin_.26_Etoposide|Cisplatin & Etoposide]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Vinblastine|Cisplatin & Vinblastine]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Vindesine|Cisplatin & Vindesine]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Vinorelbine|Cisplatin & Vinorelbine]]
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa043623 Winton et al. 2006 (JBR.10)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Cisplatin_.26_Vinorelbine|Cisplatin & Vinorelbine]]
+|style="background-color:#ff0000"|Seems to have inferior OS
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(06)70804-X/fulltext Douillard et al. 2006 (ANITA)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Cisplatin_.26_Vinorelbine|Cisplatin & Vinorelbine]]
+|style="background-color:#ff0000"|Seems to have inferior OS
 |-
 |[http://jco.ascopubs.org/content/26/31/5043.long Strauss et al. 2008 (CALGB 9633)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel|Carboplatin & Paclitaxel]]
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
@@ Line 383: / Line 337: @@
 ===References===
-# Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. [http://www.nejm.org/doi/full/10.1056/NEJMoa031644 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/14736927 PubMed]
+# Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J; International Adjuvant Lung Cancer Trial Collaborative Group. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004 Jan 22;350(4):351-60. [http://www.nejm.org/doi/full/10.1056/NEJMoa031644 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/14736927 PubMed]
-# Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, Cormier Y, Goss G, Inculet R, Vallieres E, Fry W, Bethune D, Ayoub J, Ding K, Seymour L, Graham B, Tsao MS, Gandara D, Kesler K, Demmy T, Shepherd F; National Cancer Institute of Canada Clinical Trials Group; National Cancer Institute of the United States Intergroup JBR.10 Trial Investigators. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med. 2005 Jun 23;352(25):2589-97. [http://www.nejm.org/doi/full/10.1056/NEJMoa043623 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/15972865 PubMed]
+# Winton T, Livingston R, Johnson D, Rigas J, Johnston M, Butts C, Cormier Y, Goss G, Inculet R, Vallieres E, Fry W, Bethune D, Ayoub J, Ding K, Seymour L, Graham B, Tsao MS, Gandara D, Kesler K, Demmy T, Shepherd F; National Cancer Institute of Canada Clinical Trials Group; National Cancer Institute of the United States Intergroup JBR.10 Trial Investigators. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med. 2005 Jun 23;352(25):2589-97. [http://www.nejm.org/doi/full/10.1056/NEJMoa043623 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15972865 PubMed]
-# Douillard JY, Rosell R, De Lena M, Carpagnano F, Ramlau R, Gonzáles-Larriba JL, Grodzki T, Pereira JR, Le Groumellec A, Lorusso V, Clary C, Torres AJ, Dahabreh J, Souquet PJ, Astudillo J, Fournel P, Artal-Cortes A, Jassem J, Koubkova L, His P, Riggi M, Hurteloup P. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol. 2006 Sep;7(9):719-27. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(06)70804-X/fulltext link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/16945766 PubMed]
+# Douillard JY, Rosell R, De Lena M, Carpagnano F, Ramlau R, Gonzáles-Larriba JL, Grodzki T, Pereira JR, Le Groumellec A, Lorusso V, Clary C, Torres AJ, Dahabreh J, Souquet PJ, Astudillo J, Fournel P, Artal-Cortes A, Jassem J, Koubkova L, His P, Riggi M, Hurteloup P. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol. 2006 Sep;7(9):719-27. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(06)70804-X/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16945766 PubMed]
-# Strauss GM, Herndon JE 2nd, Maddaus MA, Johnstone DW, Johnson EA, Harpole DH, Gillenwater HH, Watson DM, Sugarbaker DJ, Schilsky RL, Vokes EE, Green MR. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol. 2008 Nov 1;26(31):5043-51. Epub 2008 Sep 22. [http://jco.ascopubs.org/content/26/31/5043.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18809614 PubMed]
+<!-- Presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, June 5-8, 2004, New Orleans, LA, and at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA. -->
+# Strauss GM, Herndon JE 2nd, Maddaus MA, Johnstone DW, Johnson EA, Harpole DH, Gillenwater HH, Watson DM, Sugarbaker DJ, Schilsky RL, Vokes EE, Green MR. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group, and North Central Cancer Treatment Group Study Groups. J Clin Oncol. 2008 Nov 1;26(31):5043-51. Epub 2008 Sep 22. [http://jco.ascopubs.org/content/26/31/5043.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18809614 PubMed]
 =Chemotherapy & radiation therapy=
@@ Line 400: / Line 355: @@
 |-
 |[http://jco.ascopubs.org/content/23/25/5883.long Belani et al. 2005]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 420: / Line 370: @@
 ===References===
-# Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. [http://jco.ascopubs.org/content/23/25/5883.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16087941 PubMed]
+# Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. [http://jco.ascopubs.org/content/23/25/5883.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16087941 PubMed]
 ==Carboplatin, Paclitaxel, concurrent RT -> consolidation chemo {{#subobject:c7393d|Regimen=1}}==
@@ Line 433: / Line 383: @@
 |-
 |[http://jco.ascopubs.org/content/23/25/5883.long Belani et al. 2005]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 458: / Line 403: @@
 ===References===
-# Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. [http://jco.ascopubs.org/content/23/25/5883.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16087941 PubMed]
+# Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. [http://jco.ascopubs.org/content/23/25/5883.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16087941 PubMed]
 ==Carboplatin, Paclitaxel -> sequential RT {{#subobject:b2de53|Regimen=1}}==
@@ Line 471: / Line 416: @@
 |-
 |[http://jco.ascopubs.org/content/23/25/5883.long Belani et al. 2005]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 490: / Line 430: @@
 ===References===
-# Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. [http://jco.ascopubs.org/content/23/25/5883.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16087941 PubMed]
+# Belani CP, Choy H, Bonomi P, Scott C, Travis P, Haluschak J, Curran WJ Jr. Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol. 2005 Sep 1;23(25):5883-91. [http://jco.ascopubs.org/content/23/25/5883.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16087941 PubMed]
 ==Cisplatin, Etoposide, concurrent RT {{#subobject:743aa8|Regimen=1}}==
@@ Line 497: / Line 437: @@
 |[[#toc|back to top]]
 |}
-===Regimen {{#subobject:dcb6c1|Variant=1}}===
+===Regimen #1 {{#subobject:3ea5c6|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/20/16/3454.long Albain et al. 2002 (SWOG 9019)]
+|rowspan=2|[http://jnci.oxfordjournals.org/content/103/19/1452.long Curran et al. 2011 (RTOG 9410)]
-|<span
+|rowspan=2 style="background-color:#00cd00"|Phase III
-style="background:#EEEE00;
+|[[#Cisplatin.2C_Vinblastine.2C_concurrent_RT|Cisplatin, Vinblastine, concurrent RT]]
-padding:3px 6px 3px 6px;
+|style="background-color:#eeee00"|Seems not superior
-border-color:black;
+|-
-border-width:2px;
+|[[Non-small_cell_lung_cancer#Cisplatin.2C_Vinblastine.2C_sequential_RT|Cisplatin, Vinblastine, sequential RT]]
-border-style:solid;">Phase II</span>
+|style="background-color:#00cd00"|Might have superior OS
+|-
+|}
+====Chemoradiotherapy====
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 8, 29, 36
+*[[Etoposide (Vepesid)]] 50 mg PO BID on days 1 to 5, 8 to 12, 29 to 33, 36 to 40
+*Concurrent radiation therapy, 1.2 Gy fractions (total dose: 69.6 Gy), given twice per day for 5 days per week, starting on day 1
+'''5-week course'''
+===Regimen #2 {{#subobject:dcb6c1|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|-
+|[http://jco.ascopubs.org/content/20/16/3454.long Albain et al. 2002 (SWOG 9019)]
+|style="background-color:#eeee00"|Phase II
 |-
 |}
@@ Line 521: / Line 479: @@
 ===References===
-# Albain KS, Crowley JJ, Turrisi AT 3rd, Gandara DR, Farrar WB, Clark JI, Beasley KR, Livingston RB. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: a Southwest Oncology Group phase II study, SWOG 9019. J Clin Oncol. 2002 Aug 15;20(16):3454-60. [http://jco.ascopubs.org/content/20/16/3454.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12177106 PubMed]
+# Albain KS, Crowley JJ, Turrisi AT 3rd, Gandara DR, Farrar WB, Clark JI, Beasley KR, Livingston RB. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: a Southwest Oncology Group phase II study, SWOG 9019. J Clin Oncol. 2002 Aug 15;20(16):3454-60. [http://jco.ascopubs.org/content/20/16/3454.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12177106 PubMed]
+# Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. [http://jnci.oxfordjournals.org/content/103/19/1452.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21903745 PubMed]
 ==Cisplatin, Etoposide, concurrent RT -> consolidation chemo {{#subobject:ed64d4|Regimen=1}}==
@@ Line 534: / Line 493: @@
 |-
 |[http://jco.ascopubs.org/content/20/16/3454.long Albain et al. 2002 (SWOG 9019)]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 558: / Line 512: @@
 ===References===
-# Albain KS, Crowley JJ, Turrisi AT 3rd, Gandara DR, Farrar WB, Clark JI, Beasley KR, Livingston RB. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: a Southwest Oncology Group phase II study, SWOG 9019. J Clin Oncol. 2002 Aug 15;20(16):3454-60. [http://jco.ascopubs.org/content/20/16/3454.long link to original article] '''contains protocol'''--see note above [http://www.ncbi.nlm.nih.gov/pubmed/12177106 PubMed]
+# Albain KS, Crowley JJ, Turrisi AT 3rd, Gandara DR, Farrar WB, Clark JI, Beasley KR, Livingston RB. Concurrent cisplatin, etoposide, and chest radiotherapy in pathologic stage IIIB non-small-cell lung cancer: a Southwest Oncology Group phase II study, SWOG 9019. J Clin Oncol. 2002 Aug 15;20(16):3454-60. [http://jco.ascopubs.org/content/20/16/3454.long link to original article] '''contains protocol'''--see note above [https://www.ncbi.nlm.nih.gov/pubmed/12177106 PubMed]
 ==Cisplatin, Vinblastine, concurrent RT {{#subobject:54c5c4|Regimen=1}}==
@@ Line 570: / Line 524: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|rowspan=2|[http://jnci.oxfordjournals.org/content/103/19/1452.long Curran et al. 2011 (RTOG 9410)]
+|rowspan=2 style="background-color:#00cd00"|Phase III
+|[[#Cisplatin.2C_Etoposide.2C_concurrent_RT|Cisplatin, Etoposide, concurrent RT]]
+|style="background-color:#eeee00"|Seems not superior
 |-
-|[http://jnci.oxfordjournals.org/content/103/19/1452.long Curran et al. 2011 (RTOG 9410)]
-|<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Cisplatin.2C_Vinblastine.2C_sequential_RT|Cisplatin, Vinblastine, sequential RT]]
+|style="background-color:#00cd00"|Seems to have superior OS
 |-
 |}
@@ Line 589: / Line 543: @@
 ===References===
-# Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. [http://jnci.oxfordjournals.org/content/103/19/1452.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/21903745 PubMed]
+# Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. [http://jnci.oxfordjournals.org/content/103/19/1452.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21903745 PubMed]
 ==Cisplatin, Vinblastine, sequential RT {{#subobject:6b4fa8|Regimen=1}}==
@@ Line 601: / Line 555: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|rowspan=2|[http://jnci.oxfordjournals.org/content/103/19/1452.long Curran et al. 2011 (RTOG 9410)]
+|rowspan=2 style="background-color:#00cd00"|Phase III
+|[[#Cisplatin.2C_Etoposide.2C_concurrent_RT|Cisplatin, Etoposide, concurrent RT]]
+|style="background-color:#ff0000"|Might have inferior OS
 |-
-|[http://jnci.oxfordjournals.org/content/103/19/1452.long Curran et al. 2011 (RTOG 9410)]
-|<span
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Cisplatin.2C_Vinblastine.2C_concurrent_RT|Cisplatin, Vinblastine, concurrent RT]]
+|style="background-color:#ff0000"|Seems to have inferior OS
 |-
 |}
@@ Line 621: / Line 575: @@
 ===References===
-# Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. [http://jnci.oxfordjournals.org/content/103/19/1452.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/21903745 PubMed]
+# Curran WJ Jr, Paulus R, Langer CJ, Komaki R, Lee JS, Hauser S, Movsas B, Wasserman T, Rosenthal SA, Gore E, Machtay M, Sause W, Cox JD. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst. 2011 Oct 5;103(19):1452-60. Epub 2011 Sep 8. [http://jnci.oxfordjournals.org/content/103/19/1452.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21903745 PubMed]
 =Advanced or metastatic disease, ALK-positive=
@@ Line 637: / Line 591: @@
 |-
 ||[http://jco.ascopubs.org/content/early/2015/11/23/JCO.2015.63.9443.long Ou et al. 2015 (NP28673)]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#eeee00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |[http://meetinglibrary.asco.org/content/151415-156 Gandhi et al. 2015 (NP28761)]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#eeee00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 662: / Line 606: @@
 ===References===
 # Leena Gandhi, Alice Shaw, Shirish M. Gadgeel, Gregory Riely, Jeremy Cetnar, Howard Jack West, D. Ross Camidge, Mark A. Socinski, Alberto Chiappori, Tarek Mekhail, Bo H. Chao, Hossein Borghaei, Kathryn A. Gold, Ali Hassan Zeaiter, Walter Bordogna, Bogdana Balas, Oscar Puig, Volkmar Henschel, Sai-Hong Ignatius Ou, NP28761 Study Investigators. A phase II, open-label, multicenter study of the ALK inhibitor alectinib in an ALK+ non-small-cell lung cancer (NSCLC) U.S./Canadian population who had progressed on crizotinib (NP28761). 2015 ASCO Annual Meeting abstract 8019. [http://meetinglibrary.asco.org/content/151415-156 link to abstract]
-# Ou SI, Ahn JS, De Petris L, Govindan R, Yang JC, Hughes B, Lena H, Moro-Sibilot D, Bearz A, Ramirez SV, Mekhail T, Spira A, Bordogna W, Balas B, Morcos PN, Monnet A, Zeaiter A, Kim DW. Alectinib in Crizotinib-Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global Study. J Clin Oncol. 2015 Nov 23. [http://jco.ascopubs.org/content/early/2015/11/23/JCO.2015.63.9443.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26598747 PubMed]
+# Ou SI, Ahn JS, De Petris L, Govindan R, Yang JC, Hughes B, Lena H, Moro-Sibilot D, Bearz A, Ramirez SV, Mekhail T, Spira A, Bordogna W, Balas B, Morcos PN, Monnet A, Zeaiter A, Kim DW. Alectinib in Crizotinib-Refractory ALK-Rearranged Non-Small-Cell Lung Cancer: A Phase II Global Study. J Clin Oncol. 2015 Nov 23. [http://jco.ascopubs.org/content/early/2015/11/23/JCO.2015.63.9443.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26598747 PubMed]
 ==Ceritinib (Zykadia) {{#subobject:fe3892|Regimen=1}}==
@@ Line 676: / Line 620: @@
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1311107 Shaw et al. 2014]
-|<span
+|style="background-color:#ff0000"|Phase I
-style="background:#ff0000;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase I</span>
 |-
 |}
@@ Line 692: / Line 631: @@
 ===References===
-# Shaw AT, Kim DW, Mehra R, Tan DS, Felip E, Chow LQ, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Lau YY, Goldwasser M, Boral AL, Engelman JA. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Mar 27;370(13):1189-97. [http://www.nejm.org/doi/full/10.1056/NEJMoa1311107 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24670165 PubMed]
+# Shaw AT, Kim DW, Mehra R, Tan DS, Felip E, Chow LQ, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Lau YY, Goldwasser M, Boral AL, Engelman JA. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Mar 27;370(13):1189-97. [http://www.nejm.org/doi/full/10.1056/NEJMoa1311107 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24670165 PubMed]
 ==Crizotinib (Xalkori) {{#subobject:be5391|Regimen=1}}==
@@ Line 704: / Line 643: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1006448 Kwak et al. 2010]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#eeee00;
+|style="background-color:#d3d3d3"|
-padding:3px 6px 3px 6px;
+|style="background-color:#d3d3d3"|
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-|
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa1214886 Shaw et al. 2013]
+|rowspan=2|[http://www.nejm.org/doi/full/10.1056/NEJMoa1214886 Shaw et al. 2013]
-|<span
+|rowspan=2 style="background-color:#00cd00"|Phase III
-style="background:#00cd00;
+|[[Non-small_cell_lung_cancer#Pemetrexed_.28Alimta.29|Pemetrexed]]
-padding:3px 6px 3px 6px;
+|style="background-color:#00cd00"|Superior PFS
-border-color:black;
+|-
-border-width:2px;
+|[[Non-small_cell_lung_cancer#Docetaxel_.28Taxotere.29|Docetaxel]]
-border-style:solid;">Phase III</span>
+|style="background-color:#00cd00"|Superior PFS
-|[[Non-small_cell_lung_cancer#Pemetrexed_.28Alimta.29|Pemetrexed]]<br> [[Non-small_cell_lung_cancer#Docetaxel_.28Taxotere.29|Docetaxel]]
 |-
 |}
@@ Line 732: / Line 667: @@
 ===References===
-# Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Jänne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, Iafrate AJ. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010 Oct 28;363(18):1693-703. [http://www.nejm.org/doi/full/10.1056/NEJMoa1006448 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/20979469 PubMed]
+# Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Jänne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, Iafrate AJ. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010 Oct 28;363(18):1693-703. [http://www.nejm.org/doi/full/10.1056/NEJMoa1006448 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20979469 PubMed]
-## '''Update:''' Camidge DR, Bang YJ, Kwak EL, Iafrate AJ, Varella-Garcia M, Fox SB, Riely GJ, Solomon B, Ou SH, Kim DW, Salgia R, Fidias P, Engelman JA, Gandhi L, Jänne PA, Costa DB, Shapiro GI, Lorusso P, Ruffner K, Stephenson P, Tang Y, Wilner K, Clark JW, Shaw AT. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol. 2012 Oct;13(10):1011-9. Epub 2012 Sep 4. [http://www.sciencedirect.com/science/article/pii/S1470204512703443 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22954507 PubMed]
+## '''Update:''' Camidge DR, Bang YJ, Kwak EL, Iafrate AJ, Varella-Garcia M, Fox SB, Riely GJ, Solomon B, Ou SH, Kim DW, Salgia R, Fidias P, Engelman JA, Gandhi L, Jänne PA, Costa DB, Shapiro GI, Lorusso P, Ruffner K, Stephenson P, Tang Y, Wilner K, Clark JW, Shaw AT. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol. 2012 Oct;13(10):1011-9. Epub 2012 Sep 4. [http://www.sciencedirect.com/science/article/pii/S1470204512703443 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22954507 PubMed]
-# '''Retrospective:''' Shaw AT, Yeap BY, Solomon BJ, Riely GJ, Gainor J, Engelman JA, Shapiro GI, Costa DB, Ou SH, Butaney M, Salgia R, Maki RG, Varella-Garcia M, Doebele RC, Bang YJ, Kulig K, Selaru P, Tang Y, Wilner KD, Kwak EL, Clark JW, Iafrate AJ, Camidge DR. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol. 2011 Oct;12(11):1004-12. Epub 2011 Sep 18. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328296/ link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/21933749 PubMed]
+# '''Retrospective:''' Shaw AT, Yeap BY, Solomon BJ, Riely GJ, Gainor J, Engelman JA, Shapiro GI, Costa DB, Ou SH, Butaney M, Salgia R, Maki RG, Varella-Garcia M, Doebele RC, Bang YJ, Kulig K, Selaru P, Tang Y, Wilner KD, Kwak EL, Clark JW, Iafrate AJ, Camidge DR. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol. 2011 Oct;12(11):1004-12. Epub 2011 Sep 18. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328296/ link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21933749 PubMed]
-# Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O'Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Jänne PA. Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer. N Engl J Med. 2013 Jun 20;368(25):2385-94. Epub 2013 Jun 1. [http://www.nejm.org/doi/full/10.1056/NEJMoa1214886 link to original article] [http://www.nejm.org/doi/suppl/10.1056/NEJMoa1214886/suppl_file/nejmoa1214886_appendix.pdf link to supplementary appendix] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23724913 PubMed]
+# Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O'Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Jänne PA. Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer. N Engl J Med. 2013 Jun 20;368(25):2385-94. Epub 2013 Jun 1. [http://www.nejm.org/doi/full/10.1056/NEJMoa1214886 link to original article] [http://www.nejm.org/doi/suppl/10.1056/NEJMoa1214886/suppl_file/nejmoa1214886_appendix.pdf link to supplementary appendix] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23724913 PubMed]
 =Advanced or metastatic disease=
@@ Line 752: / Line 687: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70086-4/abstract Yang et al. 2012 (LUX-Lung 2)]
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70086-4/fulltext Yang et al. 2012 (LUX-Lung 2)]
 |style="background-color:#eeee00"|Phase II
 |style="background-color:#d3d3d3"|
@@ Line 786: / Line 721: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70087-6/abstract Miller et al. 2012 (LUX-Lung 1)]
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70087-6/fulltext Miller et al. 2012 (LUX-Lung 1)]
 |style="background-color:#00cd00"|Phase III
 |[[Non-small_cell_lung_cancer#Placebo_.28Observation.29_2|Placebo]]
@@ Line 804: / Line 739: @@
 ===References===
-# Miller VA, Hirsh V, Cadranel J, Chen YM, Park K, Kim SW, Zhou C, Su WC, Wang M, Sun Y, Heo DS, Crino L, Tan EH, Chao TY, Shahidi M, Cong XJ, Lorence RM, Yang JC. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol. 2012 May;13(5):528-38. Epub 2012 Mar 26. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70087-6/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22452896 PubMed]
+# Miller VA, Hirsh V, Cadranel J, Chen YM, Park K, Kim SW, Zhou C, Su WC, Wang M, Sun Y, Heo DS, Crino L, Tan EH, Chao TY, Shahidi M, Cong XJ, Lorence RM, Yang JC. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol. 2012 May;13(5):528-38. Epub 2012 Mar 26. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70087-6/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22452896 PubMed]
-# Yang JC, Shih JY, Su WC, Hsia TC, Tsai CM, Ou SH, Yu CJ, Chang GC, Ho CL, Sequist LV, Dudek AZ, Shahidi M, Cong XJ, Lorence RM, Yang PC, Miller VA. Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol. 2012 May;13(5):539-48. Epub 2012 Mar 26. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70086-4/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22452895 PubMed]
+# Yang JC, Shih JY, Su WC, Hsia TC, Tsai CM, Ou SH, Yu CJ, Chang GC, Ho CL, Sequist LV, Dudek AZ, Shahidi M, Cong XJ, Lorence RM, Yang PC, Miller VA. Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol. 2012 May;13(5):539-48. Epub 2012 Mar 26. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70086-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22452895 PubMed]
-# Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. Epub 2013 Jul 1. [http://jco.ascopubs.org/content/31/27/3327.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23816960 PubMed]
+# Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. Epub 2013 Jul 1. [http://jco.ascopubs.org/content/31/27/3327.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23816960 PubMed]
-## '''Subgroup analysis:''' Yang JC, Hirsh V, Schuler M, Yamamoto N, O'Byrne KJ, Mok TS, Zazulina V, Shahidi M, Lungershausen J, Massey D, Palmer M, Sequist LV. Symptom Control and Quality of Life in LUX-Lung 3: A Phase III Study of Afatinib or Cisplatin/Pemetrexed in Patients With Advanced Lung Adenocarcinoma With EGFR Mutations. J Clin Oncol. 2013 Sep 20;31(27):3342-50. Epub 2013 Jul 1. [http://jco.ascopubs.org/content/31/27/3342.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23816967 PubMed]
+## '''Subgroup analysis:''' Yang JC, Hirsh V, Schuler M, Yamamoto N, O'Byrne KJ, Mok TS, Zazulina V, Shahidi M, Lungershausen J, Massey D, Palmer M, Sequist LV. Symptom Control and Quality of Life in LUX-Lung 3: A Phase III Study of Afatinib or Cisplatin/Pemetrexed in Patients With Advanced Lung Adenocarcinoma With EGFR Mutations. J Clin Oncol. 2013 Sep 20;31(27):3342-50. Epub 2013 Jul 1. [http://jco.ascopubs.org/content/31/27/3342.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23816967 PubMed]
-# Katakami N, Atagi S, Goto K, Hida T, Horai T, Inoue A, Ichinose Y, Koboyashi K, Takeda K, Kiura K, Nishio K, Seki Y, Ebisawa R, Shahidi M, Yamamoto N. LUX-Lung 4: A Phase II Trial of Afatinib in Patients With Advanced Non-Small-Cell Lung Cancer Who Progressed During Prior Treatment With Erlotinib, Gefitinib, or Both. J Clin Oncol. 2013 Sep 20;31(27):3335-41. Epub 2013 Jul 1. [http://jco.ascopubs.org/content/31/27/3335.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23816963 PubMed]
+# Katakami N, Atagi S, Goto K, Hida T, Horai T, Inoue A, Ichinose Y, Koboyashi K, Takeda K, Kiura K, Nishio K, Seki Y, Ebisawa R, Shahidi M, Yamamoto N. LUX-Lung 4: A Phase II Trial of Afatinib in Patients With Advanced Non-Small-Cell Lung Cancer Who Progressed During Prior Treatment With Erlotinib, Gefitinib, or Both. J Clin Oncol. 2013 Sep 20;31(27):3335-41. Epub 2013 Jul 1. [http://jco.ascopubs.org/content/31/27/3335.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23816963 PubMed]
 # Soria JC, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, Göker E, Georgoulias V, Li W, Isla D, Guclu SZ, Morabito A, Min YJ, Ardizzoni A, Gadgeel SM, Wang B, Chand VK, Goss GD; LUX-Lung 8 Investigators. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015 Aug;16(8):897-907. Epub 2015 Jul 5. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00006-6/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26156651 PubMed]
-# Park K, Tan EH, O'Byrne K, Zhang L, Boyer M, Mok T, Hirsh V, Yang JC, Lee KH, Lu S, Shi Y, Kim SW, Laskin J, Kim DW, Arvis CD, Kölbeck K, Laurie SA, Tsai CM, Shahidi M, Kim M, Massey D, Zazulina V, Paz-Ares L. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016 May;17(5):577-89. Epub 2016 Apr 12. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30033-X/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/27083334 PubMed]
+# Park K, Tan EH, O'Byrne K, Zhang L, Boyer M, Mok T, Hirsh V, Yang JC, Lee KH, Lu S, Shi Y, Kim SW, Laskin J, Kim DW, Arvis CD, Kölbeck K, Laurie SA, Tsai CM, Shahidi M, Kim M, Massey D, Zazulina V, Paz-Ares L. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016 May;17(5):577-89. Epub 2016 Apr 12. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30033-X/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27083334 PubMed]
 ==Atezolizumab (Tecentriq) {{#subobject:412fc4|Regimen=1}}==
@@ Line 823: / Line 758: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)00587-0/fulltext Fehrenbacher et al. 2016 (POPLAR)]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00cd00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
 |[[#Docetaxel_.28Taxotere.29|Docetaxel]]
+|style="background-color:#00cd00"|Seems to have superior OS
 |-
 |}
@@ Line 840: / Line 772: @@
 ===References===
-# Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, Park K, Smith D, Artal-Cortes A, Lewanski C, Braiteh F, Waterkamp D, He P, Zou W, Chen DS, Yi J, Sandler A, Rittmeyer A; POPLAR Study Group. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016 Apr 30;387(10030):1837-46. Epub 2016 Mar 9. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)00587-0/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26970723 PubMed]
+# Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, Park K, Smith D, Artal-Cortes A, Lewanski C, Braiteh F, Waterkamp D, He P, Zou W, Chen DS, Yi J, Sandler A, Rittmeyer A; POPLAR Study Group. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016 Apr 30;387(10030):1837-46. Epub 2016 Mar 9. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)00587-0/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26970723 PubMed]
 ==Carboplatin & Docetaxel {{#subobject:bdce59|Regimen=1}}==
@@ Line 852: / Line 784: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|rowspan=2|[http://jco.ascopubs.org/content/21/16/3016.long Fossella et al. 2003 (TAX 326)]
+|rowspan=2 style="background-color:#00cd00"|Phase III
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Docetaxel_2|Cisplatin & Docetaxel]]
+|
 |-
-|[http://jco.ascopubs.org/content/21/16/3016.long Fossella et al. 2003 (TAX 326)]
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Vinorelbine_2|Cisplatin & Vinorelbine]]
-|<span
+|style="background-color:#eeee00"|Seems not superior
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Non-small_cell_lung_cancer#Cisplatin_.26_Docetaxel_2|Cisplatin & Docetaxel]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Vinorelbine_2|Cisplatin & Vinorelbine]]
 |-
 |}
@@ Line 870: / Line 802: @@
 ===References===
-# Fossella F, Pereira JR, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003 Aug 15;21(16):3016-24. Epub 2003 Jul 1. [http://jco.ascopubs.org/content/21/16/3016.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12837811 PubMed]
+<!-- Previously presented in part at the Annual Meeting of the American Society of Clinical Oncology (ASCO), San Francisco, CA, May 12–15, 2001; the Annual Meeting of ASCO, Orlando, FL, May 18–21, 2002; and the Congress of the European Society for Medical Oncology, Nice, France, October 18–22, 2002. -->
+# Fossella F, Pereira JR, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003 Aug 15;21(16):3016-24. Epub 2003 Jul 1. [http://jco.ascopubs.org/content/21/16/3016.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12837811 PubMed]
 ==Carboplatin & Gemcitabine {{#subobject:8669e|Regimen=1}}==
@@ Line 907: / Line 840: @@
 ===References===
-# Sederholm C, Hillerdal G, Lamberg K, Kölbeck K, Dufmats M, Westberg R, Gawande SR. Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group. J Clin Oncol. 2005 Nov 20;23(33):8380-8. [http://jco.ascopubs.org/content/23/33/8380.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16293868 PubMed]
+# Sederholm C, Hillerdal G, Lamberg K, Kölbeck K, Dufmats M, Westberg R, Gawande SR. Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group. J Clin Oncol. 2005 Nov 20;23(33):8380-8. [http://jco.ascopubs.org/content/23/33/8380.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16293868 PubMed]
 <!-- Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL; and the International Association for the Study of Lung Cancer 12th World Conference on Lung Cancer, September 2-6, 2007, Seoul, Korea. -->
-# Grønberg BH, Bremnes RM, Fløtten O, Amundsen T, Brunsvig PF, Hjelde HH, Kaasa S, von Plessen C, Stornes F, Tollåli T, Wammer F, Aasebø U, Sundstrøm S. Phase III study by the Norwegian lung cancer study group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2009 Jul 1;27(19):3217-24. Epub 2009 May 11. [http://jco.ascopubs.org/content/27/19/3217.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19433683 PubMed]
+# Grønberg BH, Bremnes RM, Fløtten O, Amundsen T, Brunsvig PF, Hjelde HH, Kaasa S, von Plessen C, Stornes F, Tollåli T, Wammer F, Aasebø U, Sundstrøm S. Phase III study by the Norwegian lung cancer study group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2009 Jul 1;27(19):3217-24. Epub 2009 May 11. [http://jco.ascopubs.org/content/27/19/3217.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19433683 PubMed]
 # Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011 Aug;12(8):735-42. Epub 2011 Jul 23. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70184-X/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21783417 PubMed]
-## '''Update:''' Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015 Sep;26(9):1877-83. Epub 2015 Jul 3. [http://annonc.oxfordjournals.org/content/early/2015/07/15/annonc.mdv276.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/26141208 PubMed]
+## '''Update:''' Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015 Sep;26(9):1877-83. Epub 2015 Jul 3. [http://annonc.oxfordjournals.org/content/early/2015/07/15/annonc.mdv276.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26141208 PubMed]
 ==Carboplatin & Paclitaxel {{#subobject:c5fbdf|Regimen=1}}==
@@ Line 923: / Line 856: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jco.ascopubs.org/content/22/11/2184.full Johnson et al. 2004]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
 |[[Non-small_cell_lung_cancer#Carboplatin.2C_Paclitaxel.2C_Bevacizumab_.28PacCBev.29|PacCBev]]
+|style="background-color:#ff0000"|Seems to have inferior TTP
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa061884 Sandler et al. 2006 (ECOG 4599)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Carboplatin.2C_Paclitaxel.2C_Bevacizumab_.28PacCBev.29|PacCBev]] -> [[Non-small_cell_lung_cancer#Bevacizumab_.28Avastin.29|Maintenance Bev]]
+|style="background-color:#ff0000"|Inferior OS
+|-
+|[http://jco.ascopubs.org/content/26/6/863.full Lilenbaum et al. 2008]
+|style="background-color:#00cd00"|Phase III
+|[[#Erlotinib_.28Tarceva.29|Erlotinib]]
+|style="background-color:#00cd00"|Seems to have superior OS
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa0810699 Mok et al. 2009 (IPASS)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[#Gefitinib_.28Iressa.29|Gefitinib]]
+|style="background-color:#ff0000"|Inferior PFS
 |-
 |[http://jco.ascopubs.org/content/30/17/2055.long Socinski et al. 2012]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel.2C_nanoparticle_albumin-bound|Carboplatin & nabPaclitaxel]]
+|style="background-color:#ff0000"|Inferior ORR
 |-
 |[http://jco.ascopubs.org/content/32/19/2059.long Langer et al. 2014]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |Carboplatin, Figitumumab, Paclitaxel
+|style="background-color:#00cd00"|Might have superior OS
 |-
 |}
@@ Line 974: / Line 893: @@
 *[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
-'''21-day cycle for up to 6 cycles'''
+'''21-day cycle for 4 to 6 cycles'''
 ''Patients in '''Socinski et al. 2012''' "could continue in the absence of progressive disease and unacceptable toxicity per the investigator's discretion."''
@@ Line 983: / Line 902: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jco.ascopubs.org/content/30/17/2046.long Lynch et al. 2012]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
 |[[Non-small_cell_lung_cancer#Carboplatin.2C_Paclitaxel.2C_Ipilimumab|Carboplatin, Paclitaxel, Ipilimumab]]
+|style="background-color:#ff0000"|Seems to have inferior PFS
 |-
 |}
@@ Line 1,008: / Line 924: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2960780-0/fulltext Quoix et al. 2011 (IFCT-0501)]
+|rowspan=2|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2960780-0/fulltext Quoix et al. 2011 (IFCT-0501)]
-|<span
+|rowspan=2 style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
+|[[Non-small_cell_lung_cancer#Gemcitabine_.28Gemzar.29|Gemcitabine]]
-padding:3px 6px 3px 6px;
+|style="background-color:#00cd00"|Superior OS
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Non-small_cell_lung_cancer#Gemcitabine_.28Gemzar.29|Gemcitabine]]<br> [[Non-small_cell_lung_cancer#Vinorelbine_.28Navelbine.29|Vinorelbine]]
 |-
-|}
+|[[Non-small_cell_lung_cancer#Vinorelbine_.28Navelbine.29|Vinorelbine]]
+|style="background-color:#00cd00"|Superior OS
+|-
+|}
 ''Study involved only patients 70 to 89 years old''
@@ Line 1,035: / Line 951: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa0810699 Mok et al. 2009 (IPASS)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[#Gefitinib_.28Iressa.29|Gefitinib]]
+|style="background-color:#ff0000"|Inferior PFS
 |-
 |}
@@ Line 1,057: / Line 970: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|rowspan=3|[http://www.nejm.org/doi/full/10.1056/NEJMoa011954 Schiller et al. 2002]
+|rowspan=3 style="background-color:#00cd00"|Phase III
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Docetaxel_2|Cisplatin & Docetaxel]]
+|style="background-color:#eeee00"|Seems not superior
+|-
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine_2|Cisplatin & Gemcitabine]]
+|style="background-color:#eeee00"|Seems not superior
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa011954 Schiller et al. 2002]
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]
-|<span
+|style="background-color:#eeee00"|Seems not superior
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Non-small_cell_lung_cancer#Cisplatin_.26_Docetaxel_2|Cisplatin & Docetaxel]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine_2|Cisplatin & Gemcitabine]]<br>[[Non-small_cell_lung_cancer#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]
 |-
 |}
@@ Line 1,075: / Line 991: @@
 ===References===
-# Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. [http://www.nejm.org/doi/full/10.1056/NEJMoa011954 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11784875 PubMed]
+# Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. [http://www.nejm.org/doi/full/10.1056/NEJMoa011954 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11784875 PubMed]
-# Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, Langer CJ, DeVore RF 3rd, Gaudreault J, Damico LA, Holmgren E, Kabbinavar F. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2004 Jun 1;22(11):2184-91. [http://jco.ascopubs.org/content/22/11/2184.full link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/15169807 PubMed]
+# Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, Langer CJ, DeVore RF 3rd, Gaudreault J, Damico LA, Holmgren E, Kabbinavar F. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2004 Jun 1;22(11):2184-91. [http://jco.ascopubs.org/content/22/11/2184.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15169807 PubMed]
-# Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14;355(24):2542-50. [http://www.nejm.org/doi/full/10.1056/NEJMoa061884 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17167137 PubMed]
+# Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14;355(24):2542-50. [http://www.nejm.org/doi/full/10.1056/NEJMoa061884 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17167137 PubMed]
-## '''Subset analysis''': Ramalingam SS, Dahlberg SE, Langer CJ, Gray R, Belani CP, Brahmer JR, Sandler AB, Schiller JH, Johnson DH; Eastern Cooperative Oncology Group. Outcomes for elderly, advanced-stage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol. 2008 Jan 1;26(1):60-5. [http://jco.ascopubs.org/content/26/1/60.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18165641 PubMed]
+## '''Subset analysis''': Ramalingam SS, Dahlberg SE, Langer CJ, Gray R, Belani CP, Brahmer JR, Sandler AB, Schiller JH, Johnson DH; Eastern Cooperative Oncology Group. Outcomes for elderly, advanced-stage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol. 2008 Jan 1;26(1):60-5. [http://jco.ascopubs.org/content/26/1/60.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18165641 PubMed]
-# Lilenbaum R, Axelrod R, Thomas S, Dowlati A, Seigel L, Albert D, Witt K, Botkin D. Randomized phase II trial of erlotinib or standard chemotherapy in patients with advanced non-small-cell lung cancer and a performance status of 2. J Clin Oncol. 2008 Feb 20;26(6):863-9. [http://jco.ascopubs.org/content/26/6/863.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18281658 PubMed]
+# Lilenbaum R, Axelrod R, Thomas S, Dowlati A, Seigel L, Albert D, Witt K, Botkin D. Randomized phase II trial of erlotinib or standard chemotherapy in patients with advanced non-small-cell lung cancer and a performance status of 2. J Clin Oncol. 2008 Feb 20;26(6):863-9. [http://jco.ascopubs.org/content/26/6/863.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18281658 PubMed]
-# Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947-57. Epub 2009 Aug 19. [http://www.nejm.org/doi/full/10.1056/NEJMoa0810699 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19692680 PubMed]
+# Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947-57. Epub 2009 Aug 19. [http://www.nejm.org/doi/full/10.1056/NEJMoa0810699 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19692680 PubMed]
-# Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, Dauba J, Debieuvre D, Souquet PJ, Bigay-Game L, Dansin E, Poudenx M, Molinier O, Vaylet F, Moro-Sibilot D, Herman D, Bennouna J, Tredaniel J, Ducoloné A, Lebitasy MP, Baudrin L, Laporte S, Milleron B; Intergroupe Francophone de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17;378(9796):1079-88. Epub 2011 Aug 8. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2960780-0/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21831418 PubMed]
+# Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, Dauba J, Debieuvre D, Souquet PJ, Bigay-Game L, Dansin E, Poudenx M, Molinier O, Vaylet F, Moro-Sibilot D, Herman D, Bennouna J, Tredaniel J, Ducoloné A, Lebitasy MP, Baudrin L, Laporte S, Milleron B; Intergroupe Francophone de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17;378(9796):1079-88. Epub 2011 Aug 8. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2960780-0/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21831418 PubMed]
-# Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012 Jun 10;30(17):2046-54. Epub 2012 Apr 30. [http://jco.ascopubs.org/content/30/17/2046.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22547592 PubMed]
+<!-- Presented in part at The Chicago Multidisciplinary Symposium in Thoracic Oncology, Chicago, IL, December 9-11, 2010, and the 14th World Congress on Lung Cancer, Amsterdam, the Netherlands, July 3-7, 2011. -->
+# Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012 Jun 10;30(17):2046-54. Epub 2012 Apr 30. [http://jco.ascopubs.org/content/30/17/2046.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22547592 PubMed]
 <!-- Presented at the 46th Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago, IL, June 4-8, 2010; the 47th Annual Meeting of ASCO, Chicago, IL, June 2-7, 2011, and 14th World Conference on Lung Cancer, Amsterdam Rai, the Netherlands, July 3-7, 2011. -->
-# Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, Hon JK, Hirsh V, Bhar P, Zhang H, Iglesias JL, Renschler MF. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2055-62. Epub 2012 Apr 30. [http://jco.ascopubs.org/content/30/17/2055.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22547591 PubMed]
+# Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, Hon JK, Hirsh V, Bhar P, Zhang H, Iglesias JL, Renschler MF. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2055-62. Epub 2012 Apr 30. [http://jco.ascopubs.org/content/30/17/2055.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22547591 PubMed]
-# Langer CJ, Novello S, Park K, Krzakowski M, Karp DD, Mok T, Benner RJ, Scranton JR, Olszanski AJ, Jassem J. Randomized, phase III trial of first-line figitumumab in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin alone in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2014 Jul 1;32(19):2059-66. Epub 2014 Jun 2.  [http://jco.ascopubs.org/content/32/19/2059.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/24888810 PubMed]
+<!-- Presented in part at the 46th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 4-8, 2010. -->
+# Langer CJ, Novello S, Park K, Krzakowski M, Karp DD, Mok T, Benner RJ, Scranton JR, Olszanski AJ, Jassem J. Randomized, phase III trial of first-line figitumumab in combination with paclitaxel and carboplatin versus paclitaxel and carboplatin alone in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2014 Jul 1;32(19):2059-66. Epub 2014 Jun 2.  [http://jco.ascopubs.org/content/32/19/2059.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24888810 PubMed]
 ==Carboplatin & Paclitaxel, nanoparticle albumin-bound {{#subobject:413b7d|Regimen=1}}==
@@ Line 1,097: / Line 1,015: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jco.ascopubs.org/content/30/17/2055.long Socinski et al. 2012]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_2|Carboplatin & Paclitaxel]]
+|style="background-color:#00cd00"|Superior ORR
 |-
 |}
@@ Line 1,115: / Line 1,030: @@
 ===References===
-# Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, Hon JK, Hirsh V, Bhar P, Zhang H, Iglesias JL, Renschler MF. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2055-62. Epub 2012 Apr 30. [http://jco.ascopubs.org/content/30/17/2055.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22547591 PubMed]
+# Socinski MA, Bondarenko I, Karaseva NA, Makhson AM, Vynnychenko I, Okamoto I, Hon JK, Hirsh V, Bhar P, Zhang H, Iglesias JL, Renschler MF. Weekly nab-paclitaxel in combination with carboplatin versus solvent-based paclitaxel plus carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: final results of a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2055-62. Epub 2012 Apr 30. [http://jco.ascopubs.org/content/30/17/2055.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22547591 PubMed]
 ==Carboplatin, Paclitaxel, Bevacizumab (PacCBev) {{#subobject:1c2c25|Regimen=1}}==
@@ Line 1,129: / Line 1,044: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jco.ascopubs.org/content/31/34/4349.long Patel et al. 2013 (PointBreak)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Carboplatin.2C_Pemetrexed.2C_Bevacizumab_.28PemCBev.29|PemCBev]] -> [[Non-small_cell_lung_cancer#Bevacizumab_.26_Pemetrexed|Maintenance PemBev]]
+|style="background-color:#ff0000"|Seems to have inferior PFS
 |-
 |}
@@ Line 1,158: / Line 1,070: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jco.ascopubs.org/content/22/11/2184.full Johnson et al. 2004]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
 |[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_2|Carboplatin & Paclitaxel]]
-|-
+|style="background-color:#00cd00"|Seems to have superior TTP
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa061884 Sandler et al. 2006 (ECOG 4599)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_2|Carboplatin & Paclitaxel]]
+|style="background-color:#00cd00"|Superior OS
 |-
 |}
@@ Line 1,190: / Line 1,094: @@
 ===References===
-# Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, Langer CJ, DeVore RF 3rd, Gaudreault J, Damico LA, Holmgren E, Kabbinavar F. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2004 Jun 1;22(11):2184-91. [http://jco.ascopubs.org/content/22/11/2184.full link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/15169807 PubMed]
+# Johnson DH, Fehrenbacher L, Novotny WF, Herbst RS, Nemunaitis JJ, Jablons DM, Langer CJ, DeVore RF 3rd, Gaudreault J, Damico LA, Holmgren E, Kabbinavar F. Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol. 2004 Jun 1;22(11):2184-91. [http://jco.ascopubs.org/content/22/11/2184.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15169807 PubMed]
-# Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14;355(24):2542-50. [http://www.nejm.org/doi/full/10.1056/NEJMoa061884 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17167137 PubMed]
+# Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14;355(24):2542-50. [http://www.nejm.org/doi/full/10.1056/NEJMoa061884 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17167137 PubMed]
-## '''Subset analysis''': Ramalingam SS, Dahlberg SE, Langer CJ, Gray R, Belani CP, Brahmer JR, Sandler AB, Schiller JH, Johnson DH; Eastern Cooperative Oncology Group. Outcomes for elderly, advanced-stage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol. 2008 Jan 1;26(1):60-5. [http://jco.ascopubs.org/content/26/1/60.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18165641 PubMed]
+## '''Subset analysis''': Ramalingam SS, Dahlberg SE, Langer CJ, Gray R, Belani CP, Brahmer JR, Sandler AB, Schiller JH, Johnson DH; Eastern Cooperative Oncology Group. Outcomes for elderly, advanced-stage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol. 2008 Jan 1;26(1):60-5. [http://jco.ascopubs.org/content/26/1/60.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18165641 PubMed]
-# Patel JD, Socinski MA, Garon EB, Reynolds CH, Spigel DR, Olsen MR, Hermann RC, Jotte RM, Beck T, Richards DA, Guba SC, Liu J, Frimodt-Moller B, John WJ, Obasaju CK, Pennella EJ, Bonomi P, Govindan R. PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. J Clin Oncol. 2013 Dec 1;31(34):4349-57. [http://jco.ascopubs.org/content/31/34/4349.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24145346 PubMed]
+<!-- Presented in part at the Chicago Multidisciplinary Symposium in Thoracic Oncology, Chicago, IL, September 6-8, 2012, and at the American Society of Clinical Oncology's Quality Care Symposium, San Diego, CA, November 30-December 1, 2012. -->
+# Patel JD, Socinski MA, Garon EB, Reynolds CH, Spigel DR, Olsen MR, Hermann RC, Jotte RM, Beck T, Richards DA, Guba SC, Liu J, Frimodt-Moller B, John WJ, Obasaju CK, Pennella EJ, Bonomi P, Govindan R. PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. J Clin Oncol. 2013 Dec 1;31(34):4349-57. [http://jco.ascopubs.org/content/31/34/4349.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24145346 PubMed]
 ==Carboplatin, Paclitaxel, Ipilimumab {{#subobject:e8ba81|Regimen=1}}==
@@ Line 1,205: / Line 1,110: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jco.ascopubs.org/content/30/17/2046.long Lynch et al. 2012]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
 |[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_2|Carboplatin & Paclitaxel]]
+|style="background-color:#00cd00"|Seems to have superior PFS
 |-
 |}
+''Note: this is the "phased" approach to this regimen.''
 ====Chemoimmunotherapy====
 *[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
 *[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
-*[[Ipilimumab (Yervoy)]] 10 mg/kg IV once on day 1 of cycles 3 to 6
+*[[Ipilimumab (Yervoy)]] as follows:
+**Cycles 3 to 6: 10 mg/kg IV once on day 1
 ====Supportive medications====
@@ Line 1,229: / Line 1,133: @@
 ===References===
-# Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012 Jun 10;30(17):2046-54. Epub 2012 Apr 30. [http://jco.ascopubs.org/content/30/17/2046.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22547592 PubMed]
+<!-- Presented in part at The Chicago Multidisciplinary Symposium in Thoracic Oncology, Chicago, IL, December 9-11, 2010, and the 14th World Congress on Lung Cancer, Amsterdam, the Netherlands, July 3-7, 2011. -->
+# Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012 Jun 10;30(17):2046-54. Epub 2012 Apr 30. [http://jco.ascopubs.org/content/30/17/2046.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22547592 PubMed]
 ==Carboplatin & Pemetrexed {{#subobject:920f46|Regimen=1}}==
@@ Line 1,244: / Line 1,149: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jco.ascopubs.org/content/30/36/4501.long Ardizzoni et al. 2012 (GOIRC 02-2006)]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
 |[[Non-small_cell_lung_cancer#Pemetrexed_.28Alimta.29|Pemetrexed]]
+|style="background-color:#eeee00"|Seems not superior
 |-
 |[http://jco.ascopubs.org/content/31/23/2849.long Zukin et al. 2013]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Pemetrexed_.28Alimta.29|Pemetrexed]]
+|style="background-color:#00cd00"|Superior OS
 |-
 |}
@@ Line 1,281: / Line 1,179: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jco.ascopubs.org/content/27/19/3217.long Grønberg et al. 2009]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Carboplatin_.26_Gemcitabine|Carboplatin & Gemcitabine]]
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
@@ Line 1,304: / Line 1,199: @@
 ===References===
 <!-- Presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, June 1-5, 2007, Chicago, IL; and the International Association for the Study of Lung Cancer 12th World Conference on Lung Cancer, September 2-6, 2007, Seoul, Korea. -->
-# Grønberg BH, Bremnes RM, Fløtten O, Amundsen T, Brunsvig PF, Hjelde HH, Kaasa S, von Plessen C, Stornes F, Tollåli T, Wammer F, Aasebø U, Sundstrøm S. Phase III study by the Norwegian lung cancer study group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2009 Jul 1;27(19):3217-24. Epub 2009 May 11. [http://jco.ascopubs.org/content/27/19/3217.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19433683 PubMed]
+# Grønberg BH, Bremnes RM, Fløtten O, Amundsen T, Brunsvig PF, Hjelde HH, Kaasa S, von Plessen C, Stornes F, Tollåli T, Wammer F, Aasebø U, Sundstrøm S. Phase III study by the Norwegian lung cancer study group: pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2009 Jul 1;27(19):3217-24. Epub 2009 May 11. [http://jco.ascopubs.org/content/27/19/3217.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19433683 PubMed]
-# Ardizzoni A, Tiseo M, Boni L, Vincent AD, Passalacqua R, Buti S, Amoroso D, Camerini A, Labianca R, Genestreti G, Boni C, Ciuffreda L, Di Costanzo F, de Marinis F, Crinò L, Santo A, Pazzola A, Barbieri F, Zilembo N, Colantonio I, Tibaldi C, Mattioli R, Cafferata MA, Camisa R, Smit EF. Pemetrexed versus pemetrexed and carboplatin as second-line chemotherapy in advanced non-small-cell lung cancer: results of the GOIRC 02-2006 randomized phase II study and pooled analysis with the NVALT7 trial. J Clin Oncol. 2012 Dec 20;30(36):4501-7. Epub 2012 Oct 29. [http://jco.ascopubs.org/content/30/36/4501.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23109689 PubMed]
+<!-- Presented at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, June 3-7, 2011; 14th World Conference on Lung Cancer, Amsterdam, the Netherlands, July 3-7, 2011; and 13th National Congress of Medical Oncology, Bologna, Italy, November 5-7, 2011. -->
-# Zukin M, Barrios CH, Rodrigues Pereira J, De Albuquerque Ribeiro R, de Mendonça Beato CA, do Nascimento YN, Murad A, Franke FA, Precivale M, de Lima Araujo LH, Da Rocha Baldotto CS, Vieira FM, Small IA, Ferreira CG, Lilenbaum RC. Randomized Phase III Trial of Single-Agent Pemetrexed Versus Carboplatin and Pemetrexed in Patients With Advanced Non-Small-Cell Lung Cancer and Eastern Cooperative Oncology Group Performance Status of 2. J Clin Oncol. 2013 Aug 10;31(23):2849-53. Epub 2013 Jun 17. [http://jco.ascopubs.org/content/31/23/2849.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23775961 PubMed]
+# Ardizzoni A, Tiseo M, Boni L, Vincent AD, Passalacqua R, Buti S, Amoroso D, Camerini A, Labianca R, Genestreti G, Boni C, Ciuffreda L, Di Costanzo F, de Marinis F, Crinò L, Santo A, Pazzola A, Barbieri F, Zilembo N, Colantonio I, Tibaldi C, Mattioli R, Cafferata MA, Camisa R, Smit EF. Pemetrexed versus pemetrexed and carboplatin as second-line chemotherapy in advanced non-small-cell lung cancer: results of the GOIRC 02-2006 randomized phase II study and pooled analysis with the NVALT7 trial. J Clin Oncol. 2012 Dec 20;30(36):4501-7. Epub 2012 Oct 29. [http://jco.ascopubs.org/content/30/36/4501.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23109689 PubMed]
+<!-- Presented at the 48th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 1-5, 2012. -->
+# Zukin M, Barrios CH, Rodrigues Pereira J, De Albuquerque Ribeiro R, de Mendonça Beato CA, do Nascimento YN, Murad A, Franke FA, Precivale M, de Lima Araujo LH, Da Rocha Baldotto CS, Vieira FM, Small IA, Ferreira CG, Lilenbaum RC. Randomized Phase III Trial of Single-Agent Pemetrexed Versus Carboplatin and Pemetrexed in Patients With Advanced Non-Small-Cell Lung Cancer and Eastern Cooperative Oncology Group Performance Status of 2. J Clin Oncol. 2013 Aug 10;31(23):2849-53. Epub 2013 Jun 17. [http://jco.ascopubs.org/content/31/23/2849.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23775961 PubMed]
 ==Carboplatin, Pemetrexed, Bevacizumab (PemCBev) {{#subobject:a4bca7|Regimen=1}}==
@@ Line 1,320: / Line 1,217: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jco.ascopubs.org/content/31/34/4349.long Patel et al. 2013 (PointBreak)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Carboplatin.2C_Paclitaxel.2C_Bevacizumab_.28PacCBev.29|PacCBev]] -> [[Non-small_cell_lung_cancer#Bevacizumab_.28Avastin.29|Maintenance Bev]]
+|style="background-color:#00cd00"|Seems to have superior PFS
 |-
 |}
@@ Line 1,345: / Line 1,239: @@
 ===References===
-# Patel JD, Socinski MA, Garon EB, Reynolds CH, Spigel DR, Olsen MR, Hermann RC, Jotte RM, Beck T, Richards DA, Guba SC, Liu J, Frimodt-Moller B, John WJ, Obasaju CK, Pennella EJ, Bonomi P, Govindan R. PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. J Clin Oncol. 2013 Dec 1;31(34):4349-57. [http://jco.ascopubs.org/content/31/34/4349.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24145346 PubMed]
+<!-- Presented in part at the Chicago Multidisciplinary Symposium in Thoracic Oncology, Chicago, IL, September 6-8, 2012, and at the American Society of Clinical Oncology's Quality Care Symposium, San Diego, CA, November 30-December 1, 2012. -->
+# Patel JD, Socinski MA, Garon EB, Reynolds CH, Spigel DR, Olsen MR, Hermann RC, Jotte RM, Beck T, Richards DA, Guba SC, Liu J, Frimodt-Moller B, John WJ, Obasaju CK, Pennella EJ, Bonomi P, Govindan R. PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. J Clin Oncol. 2013 Dec 1;31(34):4349-57. [http://jco.ascopubs.org/content/31/34/4349.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24145346 PubMed]
 ==Cisplatin & Docetaxel {{#subobject:179d86|Regimen=1}}==
@@ Line 1,357: / Line 1,252: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|rowspan=3|[http://www.nejm.org/doi/full/10.1056/NEJMoa011954 Schiller et al. 2002]
+|rowspan=3 style="background-color:#00cd00"|Phase III
+|[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_2|Carboplatin & Paclitaxel]]
+|style="background-color:#eeee00"|Seems not superior
+|-
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine_2|Cisplatin & Gemcitabine]]
+|style="background-color:#eeee00"|Seems not superior
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa011954 Schiller et al. 2002]
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]
-|<span
+|style="background-color:#eeee00"|Seems not superior
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_2|Carboplatin & Paclitaxel]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine_2|Cisplatin & Gemcitabine]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]
 |-
-|[http://jco.ascopubs.org/content/21/16/3016.long Fossella et al. 2003 (TAX 326)]
+|rowspan=2|[http://jco.ascopubs.org/content/21/16/3016.long Fossella et al. 2003 (TAX 326)]
-|<span
+|rowspan=2 style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
+|[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_2|Carboplatin & Docetaxel]]
-padding:3px 6px 3px 6px;
+|
-border-color:black;
+|-
-border-width:2px;
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Vinorelbine_2|Cisplatin & Vinorelbine]]
-border-style:solid;">Phase III</span>
+|style="background-color:#00cd00"|Seems to have superior OS
-|[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_2|Carboplatin & Docetaxel]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Vinorelbine_2|Cisplatin & Vinorelbine]]
 |-
 |}
@@ Line 1,384: / Line 1,281: @@
 ===References===
-# Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. [http://www.nejm.org/doi/full/10.1056/NEJMoa011954 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11784875 PubMed]
+# Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. [http://www.nejm.org/doi/full/10.1056/NEJMoa011954 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11784875 PubMed]
-# Fossella F, Pereira JR, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003 Aug 15;21(16):3016-24. Epub 2003 Jul 1. [http://jco.ascopubs.org/content/21/16/3016.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12837811 PubMed]
+<!-- Previously presented in part at the Annual Meeting of the American Society of Clinical Oncology (ASCO), San Francisco, CA, May 12–15, 2001; the Annual Meeting of ASCO, Orlando, FL, May 18–21, 2002; and the Congress of the European Society for Medical Oncology, Nice, France, October 18–22, 2002. -->
+# Fossella F, Pereira JR, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003 Aug 15;21(16):3016-24. Epub 2003 Jul 1. [http://jco.ascopubs.org/content/21/16/3016.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12837811 PubMed]
 ==Cisplatin & Gemcitabine {{#subobject:fb3ee0|Regimen=1}}==
@@ Line 1,398: / Line 1,296: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00021-2/fulltext Thatcher et al. 2015 (SQUIRE)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
+|[[#Cisplatin.2C_Gemcitabine.2C_Necitumumab|Cisplatin, Gemcitabine, Necitumumab]]
-padding:3px 6px 3px 6px;
+|style="background-color:#ff0000"|Seems to have inferior OS
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|Cisplatin, Gemcitabine, Necitumumab
 |-
 |}
@@ Line 1,420: / Line 1,315: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa011954 Schiller et al. 2002]
+|rowspan=3|[http://www.nejm.org/doi/full/10.1056/NEJMoa011954 Schiller et al. 2002]
-|<span
+|rowspan=3 style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
+|[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_2|Carboplatin & Paclitaxel]]
-padding:3px 6px 3px 6px;
+|style="background-color:#eeee00"|Seems not superior
-border-color:black;
+|-
-border-width:2px;
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Docetaxel_2|Cisplatin & Docetaxel]]
-border-style:solid;">Phase III</span>
+|style="background-color:#eeee00"|Seems not superior
-|[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_2|Carboplatin & Paclitaxel]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Docetaxel_2|Cisplatin & Docetaxel]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]
+|-
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Paclitaxel|Cisplatin & Paclitaxel]]
+|style="background-color:#00cd00"|Superior PFS
 |-
 |[http://jco.ascopubs.org/content/26/21/3543.full Scagliotti et al. 2008]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Cisplatin_.26_Pemetrexed_2|Cisplatin & Pemetrexed]]
+|style="background-color:#eeee00"|Seems non-inferior
 |-
 |}
+''Note: the subgroup of '''Scagliotti et al. 2008''' with adenocarcinoma seemed to have superior OS with this regimen.''
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,447: / Line 1,342: @@
 ===References===
-# Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. [http://www.nejm.org/doi/full/10.1056/NEJMoa011954 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11784875 PubMed]
+# Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. [http://www.nejm.org/doi/full/10.1056/NEJMoa011954 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11784875 PubMed]
-# Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008 Jul 20;26(21):3543-51. Epub 2008 May 27. [http://jco.ascopubs.org/content/26/21/3543.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18506025 PubMed]
+# Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008 Jul 20;26(21):3543-51. Epub 2008 May 27. [http://jco.ascopubs.org/content/26/21/3543.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18506025 PubMed]
-# Thatcher N, Hirsch FR, Luft AV, Szczesna A, Ciuleanu TE, Dediu M, Ramlau R, Galiulin RK, Bálint B, Losonczy G, Kazarnowicz A, Park K, Schumann C, Reck M, Depenbrock H, Nanda S, Kruljac-Letunic A, Kurek R, Paz-Ares L, Socinski MA; SQUIRE Investigators. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2015 Jul;16(7):763-74. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00021-2/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26045340 PubMed]
+# Thatcher N, Hirsch FR, Luft AV, Szczesna A, Ciuleanu TE, Dediu M, Ramlau R, Galiulin RK, Bálint B, Losonczy G, Kazarnowicz A, Park K, Schumann C, Reck M, Depenbrock H, Nanda S, Kruljac-Letunic A, Kurek R, Paz-Ares L, Socinski MA; SQUIRE Investigators. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2015 Jul;16(7):763-74. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00021-2/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26045340 PubMed]
 ==Cisplatin, Gemcitabine, Necitumumab {{#subobject:PYR3|Regimen=1}}==
@@ Line 1,461: / Line 1,356: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00021-2/abstract Thatcher et al. 2015 (SQUIRE)]
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00021-2/fulltext Thatcher et al. 2015 (SQUIRE)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[#Cisplatin_.26_Gemcitabine_2|Cisplatin & Gemcitabine]]
+|style="background-color:#00cd00"|Seems to have superior OS
 |-
 |}
 ''Patients had stage IV squamous non-small-cell lung cancer''
 ====Chemotherapy====
@@ Line 1,488: / Line 1,379: @@
 ===References===
-# Thatcher N, Hirsch FR, Luft AV, Szczesna A, Ciuleanu TE, Dediu M, Ramlau R, Galiulin RK, Bálint B, Losonczy G, Kazarnowicz A, Park K, Schumann C, Reck M, Depenbrock H, Nanda S, Kruljac-Letunic A, Kurek R, Paz-Ares L, Socinski MA; SQUIRE Investigators. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2015 Jul;16(7):763-74. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00021-2/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26045340 PubMed]
+# Thatcher N, Hirsch FR, Luft AV, Szczesna A, Ciuleanu TE, Dediu M, Ramlau R, Galiulin RK, Bálint B, Losonczy G, Kazarnowicz A, Park K, Schumann C, Reck M, Depenbrock H, Nanda S, Kruljac-Letunic A, Kurek R, Paz-Ares L, Socinski MA; SQUIRE Investigators. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2015 Jul;16(7):763-74. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00021-2/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26045340 PubMed]
 ==Cisplatin & Paclitaxel {{#subobject:7f19fc|Regimen=1}}==
@@ Line 1,500: / Line 1,391: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|rowspan=3|[http://www.nejm.org/doi/full/10.1056/NEJMoa011954 Schiller et al. 2002]
+|rowspan=3 style="background-color:#00cd00"|Phase III
+|[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_2|Carboplatin & Paclitaxel]]
+|style="background-color:#eeee00"|Seems not superior
+|-
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Docetaxel_2|Cisplatin & Docetaxel]]
+|style="background-color:#eeee00"|Seems not superior
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa011954 Schiller et al. 2002]
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine_2|Cisplatin & Gemcitabine]]
-|<span
+|style="background-color:#ff0000"|Inferior PFS
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_2|Carboplatin & Paclitaxel]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Docetaxel_2|Cisplatin & Docetaxel]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine_2|Cisplatin & Gemcitabine]]
 |-
 |}
 ====Chemotherapy====
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 2, '''after paclitaxel'''
 *[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV continuous infusion over 24 hours once on day 1
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 2, '''after paclitaxel'''
 '''21-day cycles'''
 ===References===
-# Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. [http://www.nejm.org/doi/full/10.1056/NEJMoa011954 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11784875 PubMed]
+# Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. [http://www.nejm.org/doi/full/10.1056/NEJMoa011954 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11784875 PubMed]
 ==Cisplatin & Pemetrexed {{#subobject:af12b4|Regimen=1}}==
@@ Line 1,530: / Line 1,424: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jco.ascopubs.org/content/26/21/3543.full Scagliotti et al. 2008]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Cisplatin_.26_Gemcitabine_2|Cisplatin & Gemcitabine]]
+|style="background-color:#eeee00"|Seems non-inferior
 |-
 |[http://jco.ascopubs.org/content/31/27/3327.long Sequist et al. 2013 (LUX-Lung 3)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Afatinib_.28Gliotrif.29|Afatinib]]
+|style="background-color:#ff0000"|Inferior PFS
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70046-X/fulltext Paz-Ares et al. 2015 (INSPIRE)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |Cisplatin, Pemetrexed, Necitumumab
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
+''Note: the subgroup of '''Scagliotti et al. 2008''' with adenocarcinoma seemed to have inferior OS with this regimen.''
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
@@ Line 1,576: / Line 1,460: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://www.sciencedirect.com/science/article/pii/S1470204512700633 Paz-Ares et al. 2012 (PARAMOUNT)]
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70063-3/fulltext Paz-Ares et al. 2012 (PARAMOUNT)]
-|<span
+|style="background-color:#eeee00"|Non-randomized portion of RCT
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Non-randomized</span>
 |-
 |}
@@ Line 1,598: / Line 1,477: @@
 ===References===
-# Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008 Jul 20;26(21):3543-51. Epub 2008 May 27. [http://jco.ascopubs.org/content/26/21/3543.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18506025 PubMed]
+# Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008 Jul 20;26(21):3543-51. Epub 2008 May 27. [http://jco.ascopubs.org/content/26/21/3543.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18506025 PubMed]
-# Paz-Ares L, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2012 Mar;13(3):247-55. Epub 2012 Feb 16. [http://www.sciencedirect.com/science/article/pii/S1470204512700633 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22341744 PubMed]
+# Paz-Ares L, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2012 Mar;13(3):247-55. Epub 2012 Feb 16. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70063-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22341744 PubMed]
-## '''Update:''' Paz-Ares LG, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. PARAMOUNT: Final Overall Survival Results of the Phase III Study of Maintenance Pemetrexed Versus Placebo Immediately After Induction Treatment With Pemetrexed Plus Cisplatin for Advanced Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2013 Aug 10;31(23):2895-902. Epub 2013 Jul 8. [http://jco.ascopubs.org/content/31/23/2870.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23835707 PubMed]
+## '''Update:''' Paz-Ares LG, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. PARAMOUNT: Final Overall Survival Results of the Phase III Study of Maintenance Pemetrexed Versus Placebo Immediately After Induction Treatment With Pemetrexed Plus Cisplatin for Advanced Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2013 Aug 10;31(23):2895-902. Epub 2013 Jul 8. [http://jco.ascopubs.org/content/31/23/2870.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23835707 PubMed]
-# Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. Epub 2013 Jul 1. [http://jco.ascopubs.org/content/31/27/3327.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23816960 PubMed]
+# Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. Epub 2013 Jul 1. [http://jco.ascopubs.org/content/31/27/3327.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23816960 PubMed]
-## '''Subgroup analysis:''' Yang JC, Hirsh V, Schuler M, Yamamoto N, O'Byrne KJ, Mok TS, Zazulina V, Shahidi M, Lungershausen J, Massey D, Palmer M, Sequist LV. Symptom Control and Quality of Life in LUX-Lung 3: A Phase III Study of Afatinib or Cisplatin/Pemetrexed in Patients With Advanced Lung Adenocarcinoma With EGFR Mutations. J Clin Oncol. 2013 Sep 20;31(27):3342-50. Epub 2013 Jul 1. [http://jco.ascopubs.org/content/31/27/3342.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23816967 PubMed]
+## '''Subgroup analysis:''' Yang JC, Hirsh V, Schuler M, Yamamoto N, O'Byrne KJ, Mok TS, Zazulina V, Shahidi M, Lungershausen J, Massey D, Palmer M, Sequist LV. Symptom Control and Quality of Life in LUX-Lung 3: A Phase III Study of Afatinib or Cisplatin/Pemetrexed in Patients With Advanced Lung Adenocarcinoma With EGFR Mutations. J Clin Oncol. 2013 Sep 20;31(27):3342-50. Epub 2013 Jul 1. [http://jco.ascopubs.org/content/31/27/3342.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23816967 PubMed]
-# Paz-Ares L, Mezger J, Ciuleanu TE, Fischer JR, von Pawel J, Provencio M, Kazarnowicz A, Losonczy G, de Castro G Jr, Szczesna A, Crino L, Reck M, Ramlau R, Ulsperger E, Schumann C, Miziara JE, Lessa ÁE, Dediu M, Bálint B, Depenbrock H, Soldatenkova V, Kurek R, Hirsch FR, Thatcher N, Socinski MA; INSPIRE investigators. Necitumumab plus pemetrexed and cisplatin as first-line therapy in
+# Paz-Ares L, Mezger J, Ciuleanu TE, Fischer JR, von Pawel J, Provencio M, Kazarnowicz A, Losonczy G, de Castro G Jr, Szczesna A, Crino L, Reck M, Ramlau R, Ulsperger E, Schumann C, Miziara JE, Lessa ÁE, Dediu M, Bálint B, Depenbrock H, Soldatenkova V, Kurek R, Hirsch FR, Thatcher N, Socinski MA; INSPIRE investigators. Necitumumab plus pemetrexed and cisplatin as first-line therapy in patients with stage IV non-squamous non-small-cell lung cancer (INSPIRE): an open-label, randomised, controlled phase 3 study. Lancet Oncol. 2015 Mar;16(3):328-37. Epub 2015 Feb 18. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70046-X/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25701171 PubMed]
-patients with stage IV non-squamous non-small-cell lung cancer (INSPIRE): an open-label, randomised, controlled phase 3 study. Lancet Oncol. 2015 Mar;16(3):328-37. Epub 2015 Feb 18. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70046-X/fulltext link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/25701171 PubMed]
 ==Cisplatin, Pemetrexed, Bevacizumab {{#subobject:836c3d|Regimen=1}}==
@@ Line 1,617: / Line 1,495: @@
 |-
 |[http://jco.ascopubs.org/content/31/24/3004.long Barlesi et al. 2013 (AVAPERL (MO22089))]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |-
 |}
@@ Line 1,640: / Line 1,513: @@
 ===References===
-# Barlesi F, Scherpereel A, Rittmeyer A, Pazzola A, Ferrer Tur N, Kim JH, Ahn MJ, Aerts JG, Gorbunova V, Vikström A, Wong EK, Perez-Moreno P, Mitchell L, Groen HJ. Randomized Phase III Trial of Maintenance Bevacizumab With or Without Pemetrexed After First-Line Induction With Bevacizumab, Cisplatin, and Pemetrexed in Advanced Nonsquamous Non-Small-Cell Lung Cancer: AVAPERL (MO22089). J Clin Oncol. 2013 Aug 20;31(24):3004-11. Epub 2013 Jul 8. [http://jco.ascopubs.org/content/31/24/3004.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23835708 PubMed]
+# Barlesi F, Scherpereel A, Rittmeyer A, Pazzola A, Ferrer Tur N, Kim JH, Ahn MJ, Aerts JG, Gorbunova V, Vikström A, Wong EK, Perez-Moreno P, Mitchell L, Groen HJ. Randomized Phase III Trial of Maintenance Bevacizumab With or Without Pemetrexed After First-Line Induction With Bevacizumab, Cisplatin, and Pemetrexed in Advanced Nonsquamous Non-Small-Cell Lung Cancer: AVAPERL (MO22089). J Clin Oncol. 2013 Aug 20;31(24):3004-11. Epub 2013 Jul 8. [http://jco.ascopubs.org/content/31/24/3004.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23835708 PubMed]
 ==Cisplatin & Vinorelbine {{#subobject:bdd6b2|Regimen=1}}==
@@ Line 1,652: / Line 1,525: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.sciencedirect.com/science/article/pii/S0140673609605699 Pirker et al. 2009 (FLEX)]
+|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60569-9/fulltext Pirker et al. 2009 (FLEX)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
+|[[#Cisplatin.2C_Vinorelbine.2C_Cetuximab|Cisplatin, Vinorelbine, Cetuximab]]
-padding:3px 6px 3px 6px;
+|style="background-color:#ff0000"|Seems to have inferior OS
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|Cetuximab, Cisplatin, Vinorelbine
 |-
 |}
@@ Line 1,674: / Line 1,544: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|rowspan=2|[http://jco.ascopubs.org/content/21/16/3016.long Fossella et al. 2003 (TAX 326)]
+|rowspan=2 style="background-color:#00cd00"|Phase III
+|[[Non-small_cell_lung_cancer#Carboplatin_.26_Docetaxel|Carboplatin & Docetaxel]]
+|style="background-color:#eeee00"|Seems not superior
 |-
-|[http://jco.ascopubs.org/content/21/16/3016.long Fossella et al. 2003 (TAX 326)]
+|[[Non-small_cell_lung_cancer#Cisplatin_.26_Docetaxel_2|Cisplatin & Docetaxel]]
-|<span
+|style="background-color:#ff0000"|Seems to have inferior OS
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Non-small_cell_lung_cancer#Carboplatin_.26_Docetaxel|Carboplatin & Docetaxel]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Docetaxel_2|Cisplatin & Docetaxel]]
 |-
 |}
@@ Line 1,692: / Line 1,562: @@
 ===References===
-# Fossella F, Pereira JR, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003 Aug 15;21(16):3016-24. Epub 2003 Jul 1. [http://jco.ascopubs.org/content/21/16/3016.long link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12837811 PubMed]
+<!-- Previously presented in part at the Annual Meeting of the American Society of Clinical Oncology (ASCO), San Francisco, CA, May 12–15, 2001; the Annual Meeting of ASCO, Orlando, FL, May 18–21, 2002; and the Congress of the European Society for Medical Oncology, Nice, France, October 18–22, 2002. -->
-# Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Yu CT, Ganul V, Roh JK, Bajetta E, O'Byrne K, de Marinis F, Eberhardt W, Goddemeier T, Emig M, Gatzemeier U; FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009 May 2;373(9674):1525-31. [http://www.sciencedirect.com/science/article/pii/S0140673609605699 link to SD article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19410716 PubMed]
+# Fossella F, Pereira JR, von Pawel J, Pluzanska A, Gorbounova V, Kaukel E, Mattson KV, Ramlau R, Szczesna A, Fidias P, Millward M, Belani CP. Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol. 2003 Aug 15;21(16):3016-24. Epub 2003 Jul 1. [http://jco.ascopubs.org/content/21/16/3016.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12837811 PubMed]
+# Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Yu CT, Ganul V, Roh JK, Bajetta E, O'Byrne K, de Marinis F, Eberhardt W, Goddemeier T, Emig M, Gatzemeier U; FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009 May 2;373(9674):1525-31. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60569-9/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19410716 PubMed]
-==Docetaxel (Taxotere) {{#subobject:fd1716|Regimen=1}}==
+==Cisplatin, Vinorelbine, Cetuximab {{#subobject:9c28e0|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#toc|back to top]]
 |}
-===Example orders===
+===Regimen {{#subobject:b4c5e3|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60569-9/fulltext Pirker et al. 2009 (FLEX)]
+|style="background-color:#00cd00"|Phase III
+|[[#Cisplatin_.26_Vinorelbine_2|Cisplatin & Vinorelbine]]
+|style="background-color:#00cd00"|Seems to have superior OS
+|-
+|}
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
+*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 8
+*[[Cetuximab (Erbitux)]] as follows:
+**Week 1: 400 mg/m<sup>2</sup> IV over 2 hours once on day 1
+**Week 2 onwards: 250 mg/m<sup>2</sup> over 1 hour once per week
+'''21-day cycle for up to 6 cycles'''
+''Cetuximab was then to continue until progression or intolerable toxicity.''
+===References===
+# Pirker R, Pereira JR, Szczesna A, von Pawel J, Krzakowski M, Ramlau R, Vynnychenko I, Park K, Yu CT, Ganul V, Roh JK, Bajetta E, O'Byrne K, de Marinis F, Eberhardt W, Goddemeier T, Emig M, Gatzemeier U; FLEX Study Team. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet. 2009 May 2;373(9674):1525-31. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)60569-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19410716 PubMed]
+==Docetaxel (Taxotere) {{#subobject:fd1716|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#toc|back to top]]
+|}
+===Example orders===
 *[[Example orders for Docetaxel (Taxotere) in non-small cell lung cancer]]
@@ Line 1,708: / Line 1,611: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jco.ascopubs.org/content/22/9/1589.full Hanna et al. 2004]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00cd00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Pemetrexed_.28Alimta.29|Pemetrexed]]
+|style="background-color:#eeee00"|Inconclusive whether non-inferior
 |-
-|[http://chestjournal.chestpubs.org/content/129/4/1031.full Chen et al. 2006]
+|[http://www.sciencedirect.com/science/article/pii/S0012369215388218 Chen et al. 2006]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00cd00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |Weekly paclitaxel
+|
 |-
 |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)61758-4/fulltext Kim et al. 2008 (INTEREST)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Gefitinib_.28Iressa.29|Gefitinib]]
+|style="background-color:#eeee00"|Seems non-inferior
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1214886 Shaw et al. 2013]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00cd00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Crizotinib_.28Xalkori.29|Crizotinib]]
+|style="background-color:#ff0000"|Inferior PFS
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70586-2/fulltext Reck et al. 2014 (LUME-Lung 1)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00cd00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |Docetaxel & Nintedanib
+|style="background-color:#ff0000"|Inferior PFS
 |-
-|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2960845-X/abstract Garon et al. 2014 (REVEL)]
+|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2960845-X/fulltext Garon et al. 2014 (REVEL)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00cd00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Docetaxel_.26_Ramucirumab|Docetaxel & Ramucirumab]]
+|style="background-color:#ff0000"|Seems to have inferior OS
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1504627 Brahmer et al. 2015 (CheckMate 017)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[#Nivolumab_.28Opdivo.29|Nivolumab]]
+|style="background-color:#ff0000"|Inferior OS
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1507643 Borghaei et al. 2015 (CheckMate 057)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[#Nivolumab_.28Opdivo.29|Nivolumab]]
+|style="background-color:#ff0000"|Inferior OS
 |-
 |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01281-7/fulltext Herbst et al. 2015 (KEYNOTE-010)]
-|<span
+|style="background-color:#00cd00"|Phase II/III
-style="background:#00cd00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II/III</span>
 |[[#Pembrolizumab_.28Keytruda.29|Pembrolizumab]]
+|style="background-color:#ff0000"|Inferior OS
 |-
 |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)00587-0/fulltext Fehrenbacher et al. 2016 (POPLAR)]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00cd00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
 |[[#Atezolizumab_.28Tecentriq.29|Atezolizumab]]
+|style="background-color:#ff0000"|Seems to have inferior OS
 |-
 |}
@@ Line 1,815: / Line 1,679: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://chestjournal.chestpubs.org/content/129/4/1031.full Chen et al. 2006]
+|[http://www.sciencedirect.com/science/article/pii/S0012369215388218 Chen et al. 2006]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |3-week docetaxel
+|
 |-
 |}
@@ Line 1,835: / Line 1,696: @@
 ===References===
-# Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, Gatzemeier U, Tsao TC, Pless M, Muller T, Lim HL, Desch C, Szondy K, Gervais R, Shaharyar, Manegold C, Paul S, Paoletti P, Einhorn L, Bunn PA Jr. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004 May 1;22(9):1589-97. [http://jco.ascopubs.org/content/22/9/1589.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15117980 PubMed]
+# Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, Gatzemeier U, Tsao TC, Pless M, Muller T, Lim HL, Desch C, Szondy K, Gervais R, Shaharyar, Manegold C, Paul S, Paoletti P, Einhorn L, Bunn PA Jr. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004 May 1;22(9):1589-97. [http://jco.ascopubs.org/content/22/9/1589.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15117980 PubMed]
-# Chen YM, Shih JF, Perng RP, Tsai CM, Whang-Peng J. A randomized trial of different docetaxel schedules in non-small cell lung cancer patients who failed previous platinum-based chemotherapy. Chest. 2006 Apr;129(4):1031-8. [http://chestjournal.chestpubs.org/content/129/4/1031.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16608954 PubMed]
+# Chen YM, Shih JF, Perng RP, Tsai CM, Whang-Peng J. A randomized trial of different docetaxel schedules in non-small cell lung cancer patients who failed previous platinum-based chemotherapy. Chest. 2006 Apr;129(4):1031-8. [http://www.sciencedirect.com/science/article/pii/S0012369215388218 link to SD article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16608954 PubMed]
-# Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Wu YL, Li LY, Watkins CL, Sellers MV, Lowe ES, Sun Y, Liao ML, Osterlind K, Reck M, Armour AA, Shepherd FA, Lippman SM, Douillard JY. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet. 2008 Nov 22;372(9652):1809-18. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)61758-4/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19027483 PubMed]
+# Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Wu YL, Li LY, Watkins CL, Sellers MV, Lowe ES, Sun Y, Liao ML, Osterlind K, Reck M, Armour AA, Shepherd FA, Lippman SM, Douillard JY. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet. 2008 Nov 22;372(9652):1809-18. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)61758-4/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19027483 PubMed]
-# Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O'Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Jänne PA. Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer. N Engl J Med. 2013 Jun 20;368(25):2385-94. Epub 2013 Jun 1. [http://www.nejm.org/doi/full/10.1056/NEJMoa1214886 link to original article] [http://www.nejm.org/doi/suppl/10.1056/NEJMoa1214886/suppl_file/nejmoa1214886_appendix.pdf link to supplementary appendix] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23724913 PubMed]
+# Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O'Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Jänne PA. Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer. N Engl J Med. 2013 Jun 20;368(25):2385-94. Epub 2013 Jun 1. [http://www.nejm.org/doi/full/10.1056/NEJMoa1214886 link to original article] [http://www.nejm.org/doi/suppl/10.1056/NEJMoa1214886/suppl_file/nejmoa1214886_appendix.pdf link to supplementary appendix] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23724913 PubMed]
-# Reck M, Kaiser R, Mellemgaard A, Douillard JY, Orlov S, Krzakowski M, von Pawel J, Gottfried M, Bondarenko I, Liao M, Gann CN, Barrueco J, Gaschler-Markefski B, Novello S; LUME-Lung 1 Study Group. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol. 2014 Feb;15(2):143-55. 2. Epub 2014 Jan 9. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70586-2/fulltext link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/24411639 PubMed]
+# Reck M, Kaiser R, Mellemgaard A, Douillard JY, Orlov S, Krzakowski M, von Pawel J, Gottfried M, Bondarenko I, Liao M, Gann CN, Barrueco J, Gaschler-Markefski B, Novello S; LUME-Lung 1 Study Group. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol. 2014 Feb;15(2):143-55. 2. Epub 2014 Jan 9. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70586-2/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24411639 PubMed]
-# Garon EB, Ciuleanu TE, Arrieta O, Prabhash K, Syrigos KN, Goksel T, Park K, Gorbunova V, Kowalyszyn RD, Pikiel J, Czyzewicz G, Orlov SV, Lewanski CR, Thomas M, Bidoli P, Dakhil S, Gans S, Kim JH, Grigorescu A, Karaseva N, Reck M, Cappuzzo F, Alexandris E, Sashegyi A, Yurasov S, Pérol M. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014 Aug 23;384(9944):665-73. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2960845-X/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24933332 PubMed]
+# Garon EB, Ciuleanu TE, Arrieta O, Prabhash K, Syrigos KN, Goksel T, Park K, Gorbunova V, Kowalyszyn RD, Pikiel J, Czyzewicz G, Orlov SV, Lewanski CR, Thomas M, Bidoli P, Dakhil S, Gans S, Kim JH, Grigorescu A, Karaseva N, Reck M, Cappuzzo F, Alexandris E, Sashegyi A, Yurasov S, Pérol M. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014 Aug 23;384(9944):665-73. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2960845-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24933332 PubMed]
-# Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Arén Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. Epub 2015 May 31. [http://www.nejm.org/doi/full/10.1056/NEJMoa1504627 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/26028407 PubMed]
+# Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Arén Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. Epub 2015 May 31. [http://www.nejm.org/doi/full/10.1056/NEJMoa1504627 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26028407 PubMed]
-# Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhäufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crinò L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Oct 22;373(17):1627-39. Epub 2015 Sep 27. [http://www.nejm.org/doi/full/10.1056/NEJMoa1507643 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/26412456 PubMed]
+# Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhäufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crinò L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Oct 22;373(17):1627-39. Epub 2015 Sep 27. [http://www.nejm.org/doi/full/10.1056/NEJMoa1507643 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26412456 PubMed]
-# Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016 Apr 9;387(10027):1540-50. Epub 2015 Dec 19. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01281-7/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26712084 PubMed]
+# Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016 Apr 9;387(10027):1540-50. Epub 2015 Dec 19. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01281-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26712084 PubMed]
-# Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, Park K, Smith D, Artal-Cortes A, Lewanski C, Braiteh F, Waterkamp D, He P, Zou W, Chen DS, Yi J, Sandler A, Rittmeyer A; POPLAR Study Group. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016 Apr 30;387(10030):1837-46. Epub 2016 Mar 9. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)00587-0/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26970723 PubMed]
+# Fehrenbacher L, Spira A, Ballinger M, Kowanetz M, Vansteenkiste J, Mazieres J, Park K, Smith D, Artal-Cortes A, Lewanski C, Braiteh F, Waterkamp D, He P, Zou W, Chen DS, Yi J, Sandler A, Rittmeyer A; POPLAR Study Group. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016 Apr 30;387(10030):1837-46. Epub 2016 Mar 9. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)00587-0/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26970723 PubMed]
 ==Docetaxel & Ramucirumab {{#subobject:7b9570|Regimen=1}}==
@@ Line 1,856: / Line 1,717: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2960845-X/abstract Garon et al. 2014 (REVEL/I4T-MC-JVBA)]
+|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2960845-X/fulltext Garon et al. 2014 (REVEL)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Docetaxel_.28Taxotere.29|Docetaxel]]
+|style="background-color:#00cd00"|Seems to have superior OS
 |-
 |}
@@ Line 1,878: / Line 1,736: @@
 ===References===
-# Garon EB, Ciuleanu TE, Arrieta O, Prabhash K, Syrigos KN, Goksel T, Park K, Gorbunova V, Kowalyszyn RD, Pikiel J, Czyzewicz G, Orlov SV, Lewanski CR, Thomas M, Bidoli P, Dakhil S, Gans S, Kim JH, Grigorescu A, Karaseva N, Reck M, Cappuzzo F, Alexandris E, Sashegyi A, Yurasov S, Pérol M. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014 Aug 23;384(9944):665-73. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2960845-X/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24933332 PubMed]
+# Garon EB, Ciuleanu TE, Arrieta O, Prabhash K, Syrigos KN, Goksel T, Park K, Gorbunova V, Kowalyszyn RD, Pikiel J, Czyzewicz G, Orlov SV, Lewanski CR, Thomas M, Bidoli P, Dakhil S, Gans S, Kim JH, Grigorescu A, Karaseva N, Reck M, Cappuzzo F, Alexandris E, Sashegyi A, Yurasov S, Pérol M. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014 Aug 23;384(9944):665-73. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2960845-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24933332 PubMed]
 ==Erlotinib (Tarceva) {{#subobject:c3c726|Regimen=1}}==
@@ Line 1,933: / Line 1,791: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893286/ Yeo et al. 2010]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893286/ Yeo et al. 2010]
 |style="background-color:#ff0000"|Retrospective
 |-
@@ Line 1,943: / Line 1,801: @@
 ===References===
-# Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):123-32. [http://www.nejm.org/doi/full/10.1056/NEJMoa050753 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16014882 PubMed]
+# Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):123-32. [http://www.nejm.org/doi/full/10.1056/NEJMoa050753 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16014882 PubMed]
-# Lilenbaum R, Axelrod R, Thomas S, Dowlati A, Seigel L, Albert D, Witt K, Botkin D. Randomized phase II trial of erlotinib or standard chemotherapy in patients with advanced non-small-cell lung cancer and a performance status of 2. J Clin Oncol. 2008 Feb 20;26(6):863-9. [http://jco.ascopubs.org/content/26/6/863.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18281658 PubMed]
+# Lilenbaum R, Axelrod R, Thomas S, Dowlati A, Seigel L, Albert D, Witt K, Botkin D. Randomized phase II trial of erlotinib or standard chemotherapy in patients with advanced non-small-cell lung cancer and a performance status of 2. J Clin Oncol. 2008 Feb 20;26(6):863-9. [http://jco.ascopubs.org/content/26/6/863.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18281658 PubMed]
-# Yeo WL, Riely GJ, Yeap BY, Lau MW, Warner JL, Bodio K, Huberman MS, Kris MG, Tenen DG, Pao W, Kobayashi S, Costa DB. Erlotinib at a dose of 25 mg daily for non-small cell lung cancers with EGFR mutations. J Thorac Oncol. 2010 Jul;5(7):1048-53. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893286/ link to PMC article] [http://www.ncbi.nlm.nih.gov/pubmed/20512075 PubMed]
+# Yeo WL, Riely GJ, Yeap BY, Lau MW, Warner JL, Bodio K, Huberman MS, Kris MG, Tenen DG, Pao W, Kobayashi S, Costa DB. Erlotinib at a dose of 25 mg daily for non-small cell lung cancers with EGFR mutations. J Thorac Oncol. 2010 Jul;5(7):1048-53. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2893286/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20512075 PubMed]
 # Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 2011 Aug;12(8):735-42. Epub 2011 Jul 23. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70184-X/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21783417 PubMed]
-## '''Update:''' Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015 Sep;26(9):1877-83. Epub 2015 Jul 3. [http://annonc.oxfordjournals.org/content/early/2015/07/15/annonc.mdv276.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/26141208 PubMed]
+## '''Update:''' Zhou C, Wu YL, Chen G, Feng J, Liu XQ, Wang C, Zhang S, Wang J, Zhou S, Ren S, Lu S, Zhang L, Hu C, Hu C, Luo Y, Chen L, Ye M, Huang J, Zhi X, Zhang Y, Xiu Q, Ma J, Zhang L, You C. Final overall survival results from a randomised, phase III study of erlotinib versus chemotherapy as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer (OPTIMAL, CTONG-0802). Ann Oncol. 2015 Sep;26(9):1877-83. Epub 2015 Jul 3. [http://annonc.oxfordjournals.org/content/early/2015/07/15/annonc.mdv276.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26141208 PubMed]
-# Scagliotti GV, Bondarenko I, Blackhall F, Barlesi F, Hsia TC, Jassem J, Milanowski J, Popat S, Sanchez-Torres JM, Novello S, Benner RJ, Green S, Molpus K, Soria JC, Shepherd FA. Randomized, phase III trial of figitumumab in combination with erlotinib versus erlotinib alone in patients with nonadenocarcinoma nonsmall-cell lung cancer. Ann Oncol. 2015 Mar;26(3):497-504. Epub 2014 Nov 13. [http://annonc.oxfordjournals.org/content/26/3/497.long link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/25395283 PubMed]
+# Scagliotti GV, Bondarenko I, Blackhall F, Barlesi F, Hsia TC, Jassem J, Milanowski J, Popat S, Sanchez-Torres JM, Novello S, Benner RJ, Green S, Molpus K, Soria JC, Shepherd FA. Randomized, phase III trial of figitumumab in combination with erlotinib versus erlotinib alone in patients with nonadenocarcinoma nonsmall-cell lung cancer. Ann Oncol. 2015 Mar;26(3):497-504. Epub 2014 Nov 13. [http://annonc.oxfordjournals.org/content/26/3/497.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25395283 PubMed]
 # Soria JC, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, Göker E, Georgoulias V, Li W, Isla D, Guclu SZ, Morabito A, Min YJ, Ardizzoni A, Gadgeel SM, Wang B, Chand VK, Goss GD; LUX-Lung 8 Investigators. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015 Aug;16(8):897-907. Epub 2015 Jul 5. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00006-6/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26156651 PubMed]
-# Urata Y, Katakami N, Morita S, Kaji R, Yoshioka H, Seto T, Satouchi M, Iwamoto Y, Kanehara M, Fujimoto D, Ikeda N, Murakami H, Daga H, Oguri T, Goto I, Imamura F, Sugawara S, Saka H, Nogami N, Negoro S, Nakagawa K, Nakanishi Y. Randomized Phase III Study Comparing Gefitinib With Erlotinib in Patients With Previously Treated Advanced Lung Adenocarcinoma: WJOG 5108L. J Clin Oncol. 2016 Sep 20;34(27):3248-57. Epub 2016 Mar 28. [http://jco.ascopubs.org/content/34/27/3248.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/27022112 PubMed]
+# Urata Y, Katakami N, Morita S, Kaji R, Yoshioka H, Seto T, Satouchi M, Iwamoto Y, Kanehara M, Fujimoto D, Ikeda N, Murakami H, Daga H, Oguri T, Goto I, Imamura F, Sugawara S, Saka H, Nogami N, Negoro S, Nakagawa K, Nakanishi Y. Randomized Phase III Study Comparing Gefitinib With Erlotinib in Patients With Previously Treated Advanced Lung Adenocarcinoma: WJOG 5108L. J Clin Oncol. 2016 Sep 20;34(27):3248-57. Epub 2016 Mar 28. [http://jco.ascopubs.org/content/34/27/3248.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27022112 PubMed]
 ==Gefitinib (Iressa) {{#subobject:fb3998|Regimen=1}}==
@@ Line 1,984: / Line 1,842: @@
 |style="background-color:#eeee00"|Seems non-inferior
 |-
-|[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887309/ Douillard, et al. 2014]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887309/ Douillard, et al. 2014]
 |style="background-color:#eeee00"|Phase IV
 |style="background-color:#d3d3d3"|
@@ Line 2,011: / Line 1,869: @@
 ===References===
-# Kris MG, Natale RB, Herbst RS, Lynch TJ Jr, Prager D, Belani CP, Schiller JH, Kelly K, Spiridonidis H, Sandler A, Albain KS, Cella D, Wolf MK, Averbuch SD, Ochs JJ, Kay AC. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA. 2003 Oct 22;290(16):2149-58. [http://jama.jamanetwork.com/article.aspx?articleid=197532 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/15118073 PubMed]
+# Kris MG, Natale RB, Herbst RS, Lynch TJ Jr, Prager D, Belani CP, Schiller JH, Kelly K, Spiridonidis H, Sandler A, Albain KS, Cella D, Wolf MK, Averbuch SD, Ochs JJ, Kay AC. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA. 2003 Oct 22;290(16):2149-58. [http://jama.jamanetwork.com/article.aspx?articleid=197532 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15118073 PubMed]
-# Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Wu YL, Li LY, Watkins CL, Sellers MV, Lowe ES, Sun Y, Liao ML, Osterlind K, Reck M, Armour AA, Shepherd FA, Lippman SM, Douillard JY. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet. 2008 Nov 22;372(9652):1809-18. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)61758-4/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19027483 PubMed]
+# Kim ES, Hirsh V, Mok T, Socinski MA, Gervais R, Wu YL, Li LY, Watkins CL, Sellers MV, Lowe ES, Sun Y, Liao ML, Osterlind K, Reck M, Armour AA, Shepherd FA, Lippman SM, Douillard JY. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet. 2008 Nov 22;372(9652):1809-18. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)61758-4/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19027483 PubMed]
-# Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947-57. Epub 2009 Aug 19. [http://www.nejm.org/doi/full/10.1056/NEJMoa0810699 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/19692680 PubMed]
+# Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947-57. Epub 2009 Aug 19. [http://www.nejm.org/doi/full/10.1056/NEJMoa0810699 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19692680 PubMed]
-# Shi Y, Zhang L, Liu X, Zhou C, Zhang L, Zhang S, Wang D, Li Q, Qin S, Hu C, Zhang Y, Chen J, Cheng Y, Feng J, Zhang H, Song Y, Wu YL, Xu N, Zhou J, Luo R, Bai C, Jin Y, Liu W, Wei Z, Tan F, Wang Y, Ding L, Dai H, Jiao S, Wang J, Liang L, Zhang W, Sun Y. Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial. Lancet Oncol. 2013 Sep;14(10):953-61. Epub 2013 Aug 13. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70355-3/fulltext link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/23948351 PubMed]
+# Shi Y, Zhang L, Liu X, Zhou C, Zhang L, Zhang S, Wang D, Li Q, Qin S, Hu C, Zhang Y, Chen J, Cheng Y, Feng J, Zhang H, Song Y, Wu YL, Xu N, Zhou J, Luo R, Bai C, Jin Y, Liu W, Wei Z, Tan F, Wang Y, Ding L, Dai H, Jiao S, Wang J, Liang L, Zhang W, Sun Y. Icotinib versus gefitinib in previously treated advanced non-small-cell lung cancer (ICOGEN): a randomised, double-blind phase 3 non-inferiority trial. Lancet Oncol. 2013 Sep;14(10):953-61. Epub 2013 Aug 13. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70355-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23948351 PubMed]
-# Douillard JY, Ostoros G, Cobo M, Ciuleanu T, McCormack R, Webster A, Milenkova T. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br J Cancer. 2014 Jan 7;110(1):55-62. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887309/ link to PMC article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24263064 PubMed]
+# Douillard JY, Ostoros G, Cobo M, Ciuleanu T, McCormack R, Webster A, Milenkova T. First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study. Br J Cancer. 2014 Jan 7;110(1):55-62. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3887309/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24263064 PubMed]
-# Park K, Tan EH, O'Byrne K, Zhang L, Boyer M, Mok T, Hirsh V, Yang JC, Lee KH, Lu S, Shi Y, Kim SW, Laskin J, Kim DW, Arvis CD, Kölbeck K, Laurie SA, Tsai CM, Shahidi M, Kim M, Massey D, Zazulina V, Paz-Ares L. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016 May;17(5):577-89. Epub 2016 Apr 12. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30033-X/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/27083334 PubMed]
+# Park K, Tan EH, O'Byrne K, Zhang L, Boyer M, Mok T, Hirsh V, Yang JC, Lee KH, Lu S, Shi Y, Kim SW, Laskin J, Kim DW, Arvis CD, Kölbeck K, Laurie SA, Tsai CM, Shahidi M, Kim M, Massey D, Zazulina V, Paz-Ares L. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016 May;17(5):577-89. Epub 2016 Apr 12. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30033-X/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27083334 PubMed]
-# Urata Y, Katakami N, Morita S, Kaji R, Yoshioka H, Seto T, Satouchi M, Iwamoto Y, Kanehara M, Fujimoto D, Ikeda N, Murakami H, Daga H, Oguri T, Goto I, Imamura F, Sugawara S, Saka H, Nogami N, Negoro S, Nakagawa K, Nakanishi Y. Randomized Phase III Study Comparing Gefitinib With Erlotinib in Patients With Previously Treated Advanced Lung Adenocarcinoma: WJOG 5108L. J Clin Oncol. 2016 Sep 20;34(27):3248-57. Epub 2016 Mar 28. [http://jco.ascopubs.org/content/34/27/3248.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/27022112 PubMed]
+# Urata Y, Katakami N, Morita S, Kaji R, Yoshioka H, Seto T, Satouchi M, Iwamoto Y, Kanehara M, Fujimoto D, Ikeda N, Murakami H, Daga H, Oguri T, Goto I, Imamura F, Sugawara S, Saka H, Nogami N, Negoro S, Nakagawa K, Nakanishi Y. Randomized Phase III Study Comparing Gefitinib With Erlotinib in Patients With Previously Treated Advanced Lung Adenocarcinoma: WJOG 5108L. J Clin Oncol. 2016 Sep 20;34(27):3248-57. Epub 2016 Mar 28. [http://jco.ascopubs.org/content/34/27/3248.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27022112 PubMed]
-# Cheng Y, Murakami H, Yang PC, He J, Nakagawa K, Kang JH, Kim JH, Wang X, Enatsu S, Puri T, Orlando M, Yang JC. Randomized Phase II Trial of Gefitinib With and Without Pemetrexed as First-Line Therapy in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations. J Clin Oncol. 2016 Sep 20;34(27):3258-66. Epub 2016 Aug 9. [http://jco.ascopubs.org/content/34/27/3258.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/27507876 PubMed]
+# Cheng Y, Murakami H, Yang PC, He J, Nakagawa K, Kang JH, Kim JH, Wang X, Enatsu S, Puri T, Orlando M, Yang JC. Randomized Phase II Trial of Gefitinib With and Without Pemetrexed as First-Line Therapy in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations. J Clin Oncol. 2016 Sep 20;34(27):3258-66. Epub 2016 Aug 9. [http://jco.ascopubs.org/content/34/27/3258.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27507876 PubMed]
 ==Gemcitabine (Gemzar) {{#subobject:21a88f|Regimen=1}}==
@@ Line 2,030: / Line 1,888: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2960780-0/fulltext Quoix et al. 2011 (IFCT-0501)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
+|[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_2|Carboplatin & Paclitaxel]]
-padding:3px 6px 3px 6px;
+|style="background-color:#ff0000"|Inferior OS
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_2|Carboplatin & Paclitaxel]]<br> [[Non-small_cell_lung_cancer#Vinorelbine_.28Navelbine.29|Vinorelbine]]
 |-
 |}
 ''Study involved only patients 70 to 89 years old''
 ====Chemotherapy====
@@ Line 2,056: / Line 1,910: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jco.ascopubs.org/content/23/33/8380.full Sederholm et al. 2005]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Carboplatin_.26_Gemcitabine|Carboplatin & Gemcitabine]]
+|style="background-color:#ff0000"|Seems to have inferior OS
 |-
 |}
@@ Line 2,077: / Line 1,928: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jnci.oxfordjournals.org/content/95/5/362.long Gridelli et al. 2003 (MILES)]
+|rowspan=2|[http://jnci.oxfordjournals.org/content/95/5/362.long Gridelli et al. 2003 (MILES)]
-|<span
+|rowspan=2 style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
+|[[Non-small_cell_lung_cancer#Gemcitabine_.26_Vinorelbine|Gemcitabine & Vinorelbine]]
-padding:3px 6px 3px 6px;
+|style="background-color:#eeee00"|Seems not superior
-border-color:black;
+|-
-border-width:2px;
+|[[Non-small_cell_lung_cancer#Vinorelbine_.28Navelbine.29|Vinorelbine]]
-border-style:solid;">Phase III</span>
+|style="background-color:#eeee00"|Seems not superior
-|[[Non-small_cell_lung_cancer#Gemcitabine_.26_Vinorelbine|Gemcitabine & Vinorelbine]]<br> [[Non-small_cell_lung_cancer#Vinorelbine_.28Navelbine.29|Vinorelbine]]
 |-
 |}
@@ Line 2,099: / Line 1,950: @@
 ===References===
-# Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, Barbera S, Ferraù F, Piazza E, Rosetti F, Clerici M, Bertetto O, Robbiati SF, Frontini L, Sacco C, Castiglione F, Favaretto A, Novello S, Migliorino MR, Gasparini G, Galetta D, Iaffaioli RV, Gebbia V; MILES Investigators. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst. 2003 Mar 5;95(5):362-72. [http://jnci.oxfordjournals.org/content/95/5/362.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12618501 PubMed]
+# Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, Barbera S, Ferraù F, Piazza E, Rosetti F, Clerici M, Bertetto O, Robbiati SF, Frontini L, Sacco C, Castiglione F, Favaretto A, Novello S, Migliorino MR, Gasparini G, Galetta D, Iaffaioli RV, Gebbia V; MILES Investigators. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst. 2003 Mar 5;95(5):362-72. [http://jnci.oxfordjournals.org/content/95/5/362.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12618501 PubMed]
-# Sederholm C, Hillerdal G, Lamberg K, Kölbeck K, Dufmats M, Westberg R, Gawande SR. Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group. J Clin Oncol. 2005 Nov 20;23(33):8380-8. [http://jco.ascopubs.org/content/23/33/8380.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16293868 PubMed]
+# Sederholm C, Hillerdal G, Lamberg K, Kölbeck K, Dufmats M, Westberg R, Gawande SR. Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group. J Clin Oncol. 2005 Nov 20;23(33):8380-8. [http://jco.ascopubs.org/content/23/33/8380.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16293868 PubMed]
-# Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, Dauba J, Debieuvre D, Souquet PJ, Bigay-Game L, Dansin E, Poudenx M, Molinier O, Vaylet F, Moro-Sibilot D, Herman D, Bennouna J, Tredaniel J, Ducoloné A, Lebitasy MP, Baudrin L, Laporte S, Milleron B; Intergroupe Francophone de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17;378(9796):1079-88. Epub 2011 Aug 8. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2960780-0/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21831418 PubMed]
+# Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, Dauba J, Debieuvre D, Souquet PJ, Bigay-Game L, Dansin E, Poudenx M, Molinier O, Vaylet F, Moro-Sibilot D, Herman D, Bennouna J, Tredaniel J, Ducoloné A, Lebitasy MP, Baudrin L, Laporte S, Milleron B; Intergroupe Francophone de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17;378(9796):1079-88. Epub 2011 Aug 8. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2960780-0/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21831418 PubMed]
 ==Gemcitabine & Vinorelbine {{#subobject:3c6eb0|Regimen=1}}==
@@ Line 2,114: / Line 1,965: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jnci.oxfordjournals.org/content/95/5/362.long Gridelli et al. 2003 (MILES)]
+|rowspan=2|[http://jnci.oxfordjournals.org/content/95/5/362.long Gridelli et al. 2003 (MILES)]
-|<span
+|rowspan=2 style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
+|[[Non-small_cell_lung_cancer#Gemcitabine_.28Gemzar.29|Gemcitabine]]
-padding:3px 6px 3px 6px;
+|style="background-color:#eeee00"|Seems not superior
-border-color:black;
+|-
-border-width:2px;
+|[[Non-small_cell_lung_cancer#Vinorelbine_.28Navelbine.29|Vinorelbine]]
-border-style:solid;">Phase III</span>
+|style="background-color:#eeee00"|Seems not superior
-|[[Non-small_cell_lung_cancer#Gemcitabine_.28Gemzar.29|Gemcitabine]]<br> [[Non-small_cell_lung_cancer#Vinorelbine_.28Navelbine.29|Vinorelbine]]
 |-
 |}
@@ Line 2,137: / Line 1,988: @@
 ===References===
-# Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, Barbera S, Ferraù F, Piazza E, Rosetti F, Clerici M, Bertetto O, Robbiati SF, Frontini L, Sacco C, Castiglione F, Favaretto A, Novello S, Migliorino MR, Gasparini G, Galetta D, Iaffaioli RV, Gebbia V; MILES Investigators. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst. 2003 Mar 5;95(5):362-72. [http://jnci.oxfordjournals.org/content/95/5/362.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12618501 PubMed]
+# Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, Barbera S, Ferraù F, Piazza E, Rosetti F, Clerici M, Bertetto O, Robbiati SF, Frontini L, Sacco C, Castiglione F, Favaretto A, Novello S, Migliorino MR, Gasparini G, Galetta D, Iaffaioli RV, Gebbia V; MILES Investigators. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst. 2003 Mar 5;95(5):362-72. [http://jnci.oxfordjournals.org/content/95/5/362.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12618501 PubMed]
 ==Osimertinib (Tagrisso) {{#subobject:PYR2|Regimen=1}}==
@@ Line 2,150: / Line 2,001: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1411817 Jänne et al. 2015 (AURA)]
-|<span
+|style="background-color:#ff0000"|Phase I
-style="background:#ff0000;
+|style="background-color:#d3d3d3"|
-padding:3px 6px 3px 6px;
+|style="background-color:#d3d3d3"|
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase I</span>
-|none
 |-
 |[https://clinicaltrials.gov/ct2/show/NCT02094261 AURA2 (ongoing)]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
+|style="background-color:#d3d3d3"|
-padding:3px 6px 3px 6px;
+|style="background-color:#d3d3d3"|
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
-|none
 |-
 |[https://clinicaltrials.gov/ct2/show/NCT02296125 FLAURA (ongoing)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[#Gefitinib_.28Iressa.29 | Gefitinib (Iressa)]] & [[#Erlotinib_.28Tarceva.29 | Erlotinib (Tarceva)]]
+|TBD
 |-
 |}
@@ Line 2,186: / Line 2,026: @@
 ===References===
 ''Non-peer-reviewed references are listed because of a lack of published peer-reviewed articles at the time of osimertinib's 11/13/2015 FDA approval.''
-# Jänne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam SS, Ahn MJ, Kim SW, Su WC, Horn L, Haggstrom D, Felip E, Kim JH, Frewer P, Cantarini M, Brown KH, Dickinson PA, Ghiorghiu S, Ranson M. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med. 2015 Apr 30;372(18):1689-99. [http://www.nejm.org/doi/full/10.1056/NEJMoa1411817 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/25923549 PubMed]
+# Jänne PA, Yang JC, Kim DW, Planchard D, Ohe Y, Ramalingam SS, Ahn MJ, Kim SW, Su WC, Horn L, Haggstrom D, Felip E, Kim JH, Frewer P, Cantarini M, Brown KH, Dickinson PA, Ghiorghiu S, Ranson M. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer. N Engl J Med. 2015 Apr 30;372(18):1689-99. [http://www.nejm.org/doi/full/10.1056/NEJMoa1411817 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25923549 PubMed]
 # [http://www.azpicentral.com/tagrisso/tagrisso.pdf Osimertinib (Tagrisso) package insert]
 # [http://library.iaslc.org/virtual-library-search?product_id=1&author=&category=&date=&session_type=&session=&presentation=&keyword=azd9291 16th World Conference on Lung Cancer abstracts MINI16.06, MINI16.07, MINI16.08.]
@@ Line 2,208: / Line 2,048: @@
 |[[Overall response rate|'''ORR''']]
 |'''Comparator'''
-|Comparator [[Overall response rate|'''ORR''']]
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |Pt Population
 |-
 |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2815%2970054-9/fulltext Rizvi et al. 2015 (CheckMate 063)]
-|<span
+|style="background-color:#eeee00"|Phase II
-style="background:#EEEE00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase II</span>
 |14% (95% CI 9 - 22)
-|None
+|style="background-color:#d3d3d3"|
-|
+|style="background-color:#d3d3d3"|
 |Chemo exposed
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1504627 Brahmer et al. 2015 (CheckMate 017)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |20% (95% CI 14 - 28)
 |[[#Docetaxel_.28Taxotere.29|Docetaxel]]
-|9% (95% CI 5 - 15)
+|style="background-color:#00cd00"|Superior OS
 |Squamous only, chemo exposed
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1507643 Borghaei et al. 2015 (CheckMate 057)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |19% (95% CI 15 - 24)
 |[[#Docetaxel_.28Taxotere.29|Docetaxel]]
-|12% (95% CI 9 - 17)
+|style="background-color:#00cd00"|Superior OS
 |Non-squamous only, chemo exposed
 |-
@@ Line 2,255: / Line 2,080: @@
 ===References===
-# Rizvi NA, Mazières J, Planchard D, Stinchcombe TE, Dy GK, Antonia SJ, Horn L, Lena H, Minenza E, Mennecier B, Otterson GA, Campos LT, Gandara DR, Levy BP, Nair SG, Zalcman G, Wolf J, Souquet PJ, Baldini E, Cappuzzo F, Chouaid C, Dowlati A, Sanborn R, Lopez-Chavez A, Grohe C, Huber RM, Harbison CT, Baudelet C, Lestini BJ, Ramalingam SS. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 2015 Feb 19. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2815%2970054-9/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/25704439 PubMed]
+# Rizvi NA, Mazières J, Planchard D, Stinchcombe TE, Dy GK, Antonia SJ, Horn L, Lena H, Minenza E, Mennecier B, Otterson GA, Campos LT, Gandara DR, Levy BP, Nair SG, Zalcman G, Wolf J, Souquet PJ, Baldini E, Cappuzzo F, Chouaid C, Dowlati A, Sanborn R, Lopez-Chavez A, Grohe C, Huber RM, Harbison CT, Baudelet C, Lestini BJ, Ramalingam SS. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 2015 Feb 19. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2815%2970054-9/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25704439 PubMed]
-# Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Arén Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. Epub 2015 May 31. [http://www.nejm.org/doi/full/10.1056/NEJMoa1504627 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/26028407 PubMed]
+# Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Arén Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. Epub 2015 May 31. [http://www.nejm.org/doi/full/10.1056/NEJMoa1504627 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26028407 PubMed]
-# Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhäufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crinò L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Oct 22;373(17):1627-39. Epub 2015 Sep 27. [http://www.nejm.org/doi/full/10.1056/NEJMoa1507643 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/26412456 PubMed]
+# Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhäufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crinò L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Oct 22;373(17):1627-39. Epub 2015 Sep 27. [http://www.nejm.org/doi/full/10.1056/NEJMoa1507643 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26412456 PubMed]
 ==P+G {{#subobject:bbe840|Regimen=1}}==
@@ Line 2,285: / Line 2,110: @@
 ===References===
-# Cheng Y, Murakami H, Yang PC, He J, Nakagawa K, Kang JH, Kim JH, Wang X, Enatsu S, Puri T, Orlando M, Yang JC. Randomized Phase II Trial of Gefitinib With and Without Pemetrexed as First-Line Therapy in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations. J Clin Oncol. 2016 Sep 20;34(27):3258-66. Epub 2016 Aug 9. [http://jco.ascopubs.org/content/34/27/3258.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/27507876 PubMed]
+# Cheng Y, Murakami H, Yang PC, He J, Nakagawa K, Kang JH, Kim JH, Wang X, Enatsu S, Puri T, Orlando M, Yang JC. Randomized Phase II Trial of Gefitinib With and Without Pemetrexed as First-Line Therapy in Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer With Activating Epidermal Growth Factor Receptor Mutations. J Clin Oncol. 2016 Sep 20;34(27):3258-66. Epub 2016 Aug 9. [http://jco.ascopubs.org/content/34/27/3258.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27507876 PubMed]
 ==Pembrolizumab (Keytruda) {{#subobject:430dc7|Regimen=1}}==
@@ Line 2,298: / Line 2,123: @@
 |[[Overall response rate|'''ORR''']]
 |'''Comparator'''
-|Comparator [[Overall response rate|'''ORR''']]
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |Pt Population
 |-
@@ Line 2,306: / Line 2,131: @@
 mg/kg: 19% (95% CI 15 - 23)
 |[[#Docetaxel_.28Taxotere.29|Docetaxel]]
-|9% (95% CI 7 - 13)
+|style="background-color:#00cd00"|Superior OS
 |Chemo exposed
 |-
@@ Line 2,316: / Line 2,141: @@
 ===References===
-# Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn MJ, Felip E, Lee JS, Hellmann MD, Hamid O, Goldman JW, Soria JC, Dolled-Filhart M, Rutledge RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator K, Gandhi L; KEYNOTE-001 Investigators. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015 May 21;372(21):2018-28. Epub 2015 Apr 19. [http://www.nejm.org/doi/full/10.1056/NEJMoa1501824 link to original article] [http://www.ncbi.nlm.nih.gov/pubmed/25891174 PubMed]
+# Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn MJ, Felip E, Lee JS, Hellmann MD, Hamid O, Goldman JW, Soria JC, Dolled-Filhart M, Rutledge RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator K, Gandhi L; KEYNOTE-001 Investigators. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015 May 21;372(21):2018-28. Epub 2015 Apr 19. [http://www.nejm.org/doi/full/10.1056/NEJMoa1501824 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25891174 PubMed]
-# Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016 Apr 9;387(10027):1540-50. Epub 2015 Dec 19. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01281-7/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26712084 PubMed]
+# Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016 Apr 9;387(10027):1540-50. Epub 2015 Dec 19. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01281-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26712084 PubMed]
 ==Pemetrexed (Alimta) {{#subobject:615e55|Regimen=1}}==
@@ Line 2,332: / Line 2,157: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jco.ascopubs.org/content/22/9/1589.full Hanna et al. 2004]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Docetaxel_.28Taxotere.29|Docetaxel]]
+|style="background-color:#eeee00"|Inconclusive whether non-inferior
 |-
 |[http://jco.ascopubs.org/content/30/36/4501.long Ardizzoni et al. 2012 (GOIRC 02-2006)]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
 |[[Non-small_cell_lung_cancer#Carboplatin_.26_Pemetrexed|Carboplatin & Pemetrexed]]
+|style="background-color:#eeee00"|Seems not superior
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa1214886 Shaw et al. 2013]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Crizotinib_.28Xalkori.29|Crizotinib]]
+|style="background-color:#ff0000"|Inferior PFS
 |-
 |[http://jco.ascopubs.org/content/31/23/2849.long Zukin et al. 2013]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Carboplatin_.26_Pemetrexed|Carboplatin & Pemetrexed]]
+|style="background-color:#ff0000"|Inferior OS
 |-
 |}
@@ Line 2,385: / Line 2,195: @@
 ===References===
-# Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, Gatzemeier U, Tsao TC, Pless M, Muller T, Lim HL, Desch C, Szondy K, Gervais R, Shaharyar, Manegold C, Paul S, Paoletti P, Einhorn L, Bunn PA Jr. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004 May 1;22(9):1589-97. [http://jco.ascopubs.org/content/22/9/1589.full link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/15117980 PubMed]
+# Hanna N, Shepherd FA, Fossella FV, Pereira JR, De Marinis F, von Pawel J, Gatzemeier U, Tsao TC, Pless M, Muller T, Lim HL, Desch C, Szondy K, Gervais R, Shaharyar, Manegold C, Paul S, Paoletti P, Einhorn L, Bunn PA Jr. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol. 2004 May 1;22(9):1589-97. [http://jco.ascopubs.org/content/22/9/1589.full link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15117980 PubMed]
-# Ardizzoni A, Tiseo M, Boni L, Vincent AD, Passalacqua R, Buti S, Amoroso D, Camerini A, Labianca R, Genestreti G, Boni C, Ciuffreda L, Di Costanzo F, de Marinis F, Crinò L, Santo A, Pazzola A, Barbieri F, Zilembo N, Colantonio I, Tibaldi C, Mattioli R, Cafferata MA, Camisa R, Smit EF. Pemetrexed versus pemetrexed and carboplatin as second-line chemotherapy in advanced non-small-cell lung cancer: results of the GOIRC 02-2006 randomized phase II study and pooled analysis with the NVALT7 trial. J Clin Oncol. 2012 Dec 20;30(36):4501-7. Epub 2012 Oct 29. [http://jco.ascopubs.org/content/30/36/4501.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23109689 PubMed]
+<!-- Presented at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, June 3-7, 2011; 14th World Conference on Lung Cancer, Amsterdam, the Netherlands, July 3-7, 2011; and 13th National Congress of Medical Oncology, Bologna, Italy, November 5-7, 2011. -->
-# Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O'Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Jänne PA. Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer. N Engl J Med. 2013 Jun 20;368(25):2385-94. Epub 2013 Jun 1. [http://www.nejm.org/doi/full/10.1056/NEJMoa1214886 link to original article] [http://www.nejm.org/doi/suppl/10.1056/NEJMoa1214886/suppl_file/nejmoa1214886_appendix.pdf link to supplementary appendix] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23724913 PubMed]
+# Ardizzoni A, Tiseo M, Boni L, Vincent AD, Passalacqua R, Buti S, Amoroso D, Camerini A, Labianca R, Genestreti G, Boni C, Ciuffreda L, Di Costanzo F, de Marinis F, Crinò L, Santo A, Pazzola A, Barbieri F, Zilembo N, Colantonio I, Tibaldi C, Mattioli R, Cafferata MA, Camisa R, Smit EF. Pemetrexed versus pemetrexed and carboplatin as second-line chemotherapy in advanced non-small-cell lung cancer: results of the GOIRC 02-2006 randomized phase II study and pooled analysis with the NVALT7 trial. J Clin Oncol. 2012 Dec 20;30(36):4501-7. Epub 2012 Oct 29. [http://jco.ascopubs.org/content/30/36/4501.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23109689 PubMed]
-# Zukin M, Barrios CH, Rodrigues Pereira J, De Albuquerque Ribeiro R, de Mendonça Beato CA, do Nascimento YN, Murad A, Franke FA, Precivale M, de Lima Araujo LH, Da Rocha Baldotto CS, Vieira FM, Small IA, Ferreira CG, Lilenbaum RC. Randomized Phase III Trial of Single-Agent Pemetrexed Versus Carboplatin and Pemetrexed in Patients With Advanced Non-Small-Cell Lung Cancer and Eastern Cooperative Oncology Group Performance Status of 2. J Clin Oncol. 2013 Aug 10;31(23):2849-53. Epub 2013 Jun 17. [http://jco.ascopubs.org/content/31/23/2849.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23775961 PubMed]
+# Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, De Pas T, Besse B, Solomon BJ, Blackhall F, Wu YL, Thomas M, O'Byrne KJ, Moro-Sibilot D, Camidge DR, Mok T, Hirsh V, Riely GJ, Iyer S, Tassell V, Polli A, Wilner KD, Jänne PA. Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer. N Engl J Med. 2013 Jun 20;368(25):2385-94. Epub 2013 Jun 1. [http://www.nejm.org/doi/full/10.1056/NEJMoa1214886 link to original article] [http://www.nejm.org/doi/suppl/10.1056/NEJMoa1214886/suppl_file/nejmoa1214886_appendix.pdf link to supplementary appendix] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23724913 PubMed]
+<!-- Presented at the 48th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 1-5, 2012. -->
+# Zukin M, Barrios CH, Rodrigues Pereira J, De Albuquerque Ribeiro R, de Mendonça Beato CA, do Nascimento YN, Murad A, Franke FA, Precivale M, de Lima Araujo LH, Da Rocha Baldotto CS, Vieira FM, Small IA, Ferreira CG, Lilenbaum RC. Randomized Phase III Trial of Single-Agent Pemetrexed Versus Carboplatin and Pemetrexed in Patients With Advanced Non-Small-Cell Lung Cancer and Eastern Cooperative Oncology Group Performance Status of 2. J Clin Oncol. 2013 Aug 10;31(23):2849-53. Epub 2013 Jun 17. [http://jco.ascopubs.org/content/31/23/2849.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23775961 PubMed]
 ==Placebo (Observation) {{#subobject:ac6331|Regimen=1}}==
@@ Line 2,401: / Line 2,213: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jnci.oxfordjournals.org/content/91/1/66.long Elderly Lung Cancer Vinorelbine Italian Study Group, 1999]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Vinorelbine_.28Navelbine.29|Vinorelbine]]
+|style="background-color:#ff0000"|Seems to have inferior OS
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa050753 Shepherd et al. 2005 (NCIC CTG BR.21)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Erlotinib_.28Tarceva.29|Erlotinib]]
+|style="background-color:#ff0000"|Inferior OS
 |-
-|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70087-6/abstract Miller et al. 2012 (LUX-Lung 1)]
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70087-6/fulltext Miller et al. 2012 (LUX-Lung 1)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Afatinib_.28Gliotrif.29|Afatinib]]
+|style="background-color:#ff0000"|Inferior PFS
 |-
 |}
@@ Line 2,434: / Line 2,235: @@
 ===References===
-# The Elderly Lung Cancer Vinorelbine Italian Study Group. Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. J Natl Cancer Inst. 1999 Jan 6;91(1):66-72. [http://jnci.oxfordjournals.org/content/91/1/66.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9890172 PubMed]
+# The Elderly Lung Cancer Vinorelbine Italian Study Group. Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. J Natl Cancer Inst. 1999 Jan 6;91(1):66-72. [http://jnci.oxfordjournals.org/content/91/1/66.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9890172 PubMed]
-# Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):123-32. [http://www.nejm.org/doi/full/10.1056/NEJMoa050753 link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/16014882 PubMed]
+# Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, van Kooten M, Dediu M, Findlay B, Tu D, Johnston D, Bezjak A, Clark G, Santabárbara P, Seymour L; National Cancer Institute of Canada Clinical Trials Group. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005 Jul 14;353(2):123-32. [http://www.nejm.org/doi/full/10.1056/NEJMoa050753 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16014882 PubMed]
-# Miller VA, Hirsh V, Cadranel J, Chen YM, Park K, Kim SW, Zhou C, Su WC, Wang M, Sun Y, Heo DS, Crino L, Tan EH, Chao TY, Shahidi M, Cong XJ, Lorence RM, Yang JC. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol. 2012 May;13(5):528-38. Epub 2012 Mar 26. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70087-6/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22452896 PubMed]
+# Miller VA, Hirsh V, Cadranel J, Chen YM, Park K, Kim SW, Zhou C, Su WC, Wang M, Sun Y, Heo DS, Crino L, Tan EH, Chao TY, Shahidi M, Cong XJ, Lorence RM, Yang JC. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol. 2012 May;13(5):528-38. Epub 2012 Mar 26. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70087-6/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22452896 PubMed]
 ==Vinorelbine (Navelbine) {{#subobject:aa0ce0|Regimen=1}}==
@@ Line 2,448: / Line 2,249: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2960780-0/fulltext Quoix et al. 2011 (IFCT-0501)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
+|[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_2|Carboplatin & Paclitaxel]]
-padding:3px 6px 3px 6px;
+|style="background-color:#ff0000"|Inferior OS
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
-|[[Non-small_cell_lung_cancer#Carboplatin_.26_Paclitaxel_2|Carboplatin & Paclitaxel]]<br> [[Non-small_cell_lung_cancer#Gemcitabine_.28Gemzar.29|Gemcitabine]]
 |-
 |}
 ''Study involved only patients 70 to 89 years old''
 ====Chemotherapy====
@@ Line 2,474: / Line 2,271: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://jnci.oxfordjournals.org/content/91/1/66.long Elderly Lung Cancer Vinorelbine Italian Study Group, 1999]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Placebo_.28Observation.29_2|Supportive care]]
+|style="background-color:#00cd00"|Seems to have superior OS
 |-
-|[http://jnci.oxfordjournals.org/content/95/5/362.long Gridelli et al. 2003 (MILES)]
+|rowspan=2|[http://jnci.oxfordjournals.org/content/95/5/362.long Gridelli et al. 2003 (MILES)]
-|<span
+|rowspan=2 style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
+|[[Non-small_cell_lung_cancer#Gemcitabine_.28Gemzar.29|Gemcitabine]]
-padding:3px 6px 3px 6px;
+|style="background-color:#eeee00"|Seems not superior
-border-color:black;
+|-
-border-width:2px;
+|[[Non-small_cell_lung_cancer#Gemcitabine_.26_Vinorelbine|Gemcitabine & Vinorelbine]]
-border-style:solid;">Phase III</span>
+|style="background-color:#eeee00"|Seems not superior
-|[[Non-small_cell_lung_cancer#Gemcitabine_.28Gemzar.29|Gemcitabine]]<br> [[Non-small_cell_lung_cancer#Gemcitabine_.26_Vinorelbine|Gemcitabine & Vinorelbine]]
 |-
 |}
@@ Line 2,511: / Line 2,304: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://annonc.oxfordjournals.org/content/12/10/1375.long Jassem et al. 2001]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
 |Oral vinorelbine
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
@@ Line 2,537: / Line 2,327: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
 |[http://annonc.oxfordjournals.org/content/12/10/1375.long Jassem et al. 2001]
-|<span
+|style="background-color:#00cd00"|Randomized Phase II
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Randomized Phase II</span>
 |Intravenous vinorelbine
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
@@ Line 2,559: / Line 2,346: @@
 ===References===
-# The Elderly Lung Cancer Vinorelbine Italian Study Group. Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. J Natl Cancer Inst. 1999 Jan 6;91(1):66-72. [http://jnci.oxfordjournals.org/content/91/1/66.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/9890172 PubMed]
+# The Elderly Lung Cancer Vinorelbine Italian Study Group. Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. J Natl Cancer Inst. 1999 Jan 6;91(1):66-72. [http://jnci.oxfordjournals.org/content/91/1/66.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9890172 PubMed]
-# Jassem J, Ramlau R, Karnicka-Mlodkowska H, Krawczyk K, Krzakowski M, Zatloukal P, Lemarié E, Hartmann W, Novakova L, O'Brien M, Depierr A. A multicenter randomized phase II study of oral vs. intravenous vinorelbine in advanced non-small-cell lung cancer patients. Ann Oncol. 2001 Oct;12(10):1375-81. [http://annonc.oxfordjournals.org/content/12/10/1375.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/11762807 PubMed]
+# Jassem J, Ramlau R, Karnicka-Mlodkowska H, Krawczyk K, Krzakowski M, Zatloukal P, Lemarié E, Hartmann W, Novakova L, O'Brien M, Depierr A. A multicenter randomized phase II study of oral vs. intravenous vinorelbine in advanced non-small-cell lung cancer patients. Ann Oncol. 2001 Oct;12(10):1375-81. [http://annonc.oxfordjournals.org/content/12/10/1375.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11762807 PubMed]
-# Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, Barbera S, Ferraù F, Piazza E, Rosetti F, Clerici M, Bertetto O, Robbiati SF, Frontini L, Sacco C, Castiglione F, Favaretto A, Novello S, Migliorino MR, Gasparini G, Galetta D, Iaffaioli RV, Gebbia V; MILES Investigators. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst. 2003 Mar 5;95(5):362-72. [http://jnci.oxfordjournals.org/content/95/5/362.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/12618501 PubMed]
+# Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, Barbera S, Ferraù F, Piazza E, Rosetti F, Clerici M, Bertetto O, Robbiati SF, Frontini L, Sacco C, Castiglione F, Favaretto A, Novello S, Migliorino MR, Gasparini G, Galetta D, Iaffaioli RV, Gebbia V; MILES Investigators. Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst. 2003 Mar 5;95(5):362-72. [http://jnci.oxfordjournals.org/content/95/5/362.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12618501 PubMed]
-# Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, Dauba J, Debieuvre D, Souquet PJ, Bigay-Game L, Dansin E, Poudenx M, Molinier O, Vaylet F, Moro-Sibilot D, Herman D, Bennouna J, Tredaniel J, Ducoloné A, Lebitasy MP, Baudrin L, Laporte S, Milleron B; Intergroupe Francophone de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17;378(9796):1079-88. Epub 2011 Aug 8. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2960780-0/fulltext link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/21831418 PubMed]
+# Quoix E, Zalcman G, Oster JP, Westeel V, Pichon E, Lavolé A, Dauba J, Debieuvre D, Souquet PJ, Bigay-Game L, Dansin E, Poudenx M, Molinier O, Vaylet F, Moro-Sibilot D, Herman D, Bennouna J, Tredaniel J, Ducoloné A, Lebitasy MP, Baudrin L, Laporte S, Milleron B; Intergroupe Francophone de Cancérologie Thoracique. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial. Lancet. 2011 Sep 17;378(9796):1079-88. Epub 2011 Aug 8. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2960780-0/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21831418 PubMed]
 =Maintenance=
@@ Line 2,580: / Line 2,367: @@
 |-
 |[http://jco.ascopubs.org/content/31/24/3004.long Barlesi et al. 2013 (AVAPERL (MO22089))]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Bevacizumab_.26_Pemetrexed|Bevacizumab & Pemetrexed maintenance]]
-|<span
+|style="background-color:#ff0000"|Inferior PFS
-style="background:#ff0000;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Inferior PFS</span>
 |-
 |}
@@ Line 2,608: / Line 2,385: @@
 |-
 |[http://www.nejm.org/doi/full/10.1056/NEJMoa061884 Sandler et al. 2006 (ECOG 4599)]
-|<span
+|style="background-color:#eeee00"|Non-randomized portion of RCT
-style="background:#eeee00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Non-randomized</span>
 |-
 |[http://jco.ascopubs.org/content/31/34/4349.long Patel et al. 2013 (PointBreak)]
-|<span
+|style="background-color:#eeee00"|Non-randomized portion of RCT
-style="background:#eeee00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Non-randomized</span>
 |-
 |}
@@ Line 2,632: / Line 2,399: @@
 ===References===
-# Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14;355(24):2542-50. [http://www.nejm.org/doi/full/10.1056/NEJMoa061884 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17167137 PubMed]
+# Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006 Dec 14;355(24):2542-50. [http://www.nejm.org/doi/full/10.1056/NEJMoa061884 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17167137 PubMed]
-## '''Subset analysis''': Ramalingam SS, Dahlberg SE, Langer CJ, Gray R, Belani CP, Brahmer JR, Sandler AB, Schiller JH, Johnson DH; Eastern Cooperative Oncology Group. Outcomes for elderly, advanced-stage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol. 2008 Jan 1;26(1):60-5. [http://jco.ascopubs.org/content/26/1/60.full link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/18165641 PubMed]
+## '''Subset analysis''': Ramalingam SS, Dahlberg SE, Langer CJ, Gray R, Belani CP, Brahmer JR, Sandler AB, Schiller JH, Johnson DH; Eastern Cooperative Oncology Group. Outcomes for elderly, advanced-stage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol. 2008 Jan 1;26(1):60-5. [http://jco.ascopubs.org/content/26/1/60.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18165641 PubMed]
-# Barlesi F, Scherpereel A, Rittmeyer A, Pazzola A, Ferrer Tur N, Kim JH, Ahn MJ, Aerts JG, Gorbunova V, Vikström A, Wong EK, Perez-Moreno P, Mitchell L, Groen HJ. Randomized Phase III Trial of Maintenance Bevacizumab With or Without Pemetrexed After First-Line Induction With Bevacizumab, Cisplatin, and Pemetrexed in Advanced Nonsquamous Non-Small-Cell Lung Cancer: AVAPERL (MO22089). J Clin Oncol. 2013 Aug 20;31(24):3004-11. Epub 2013 Jul 8. [http://jco.ascopubs.org/content/31/24/3004.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23835708 PubMed]
+# Barlesi F, Scherpereel A, Rittmeyer A, Pazzola A, Ferrer Tur N, Kim JH, Ahn MJ, Aerts JG, Gorbunova V, Vikström A, Wong EK, Perez-Moreno P, Mitchell L, Groen HJ. Randomized Phase III Trial of Maintenance Bevacizumab With or Without Pemetrexed After First-Line Induction With Bevacizumab, Cisplatin, and Pemetrexed in Advanced Nonsquamous Non-Small-Cell Lung Cancer: AVAPERL (MO22089). J Clin Oncol. 2013 Aug 20;31(24):3004-11. Epub 2013 Jul 8. [http://jco.ascopubs.org/content/31/24/3004.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23835708 PubMed]
-# Patel JD, Socinski MA, Garon EB, Reynolds CH, Spigel DR, Olsen MR, Hermann RC, Jotte RM, Beck T, Richards DA, Guba SC, Liu J, Frimodt-Moller B, John WJ, Obasaju CK, Pennella EJ, Bonomi P, Govindan R. PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. J Clin Oncol. 2013 Dec 1;31(34):4349-57. [http://jco.ascopubs.org/content/31/34/4349.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24145346 PubMed]
+<!-- Presented in part at the Chicago Multidisciplinary Symposium in Thoracic Oncology, Chicago, IL, September 6-8, 2012, and at the American Society of Clinical Oncology's Quality Care Symposium, San Diego, CA, November 30-December 1, 2012. -->
+# Patel JD, Socinski MA, Garon EB, Reynolds CH, Spigel DR, Olsen MR, Hermann RC, Jotte RM, Beck T, Richards DA, Guba SC, Liu J, Frimodt-Moller B, John WJ, Obasaju CK, Pennella EJ, Bonomi P, Govindan R. PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. J Clin Oncol. 2013 Dec 1;31(34):4349-57. [http://jco.ascopubs.org/content/31/34/4349.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24145346 PubMed]
 ==Bevacizumab & Pemetrexed {{#subobject:db5671|Regimen=1}}==
@@ Line 2,651: / Line 2,419: @@
 |-
 |[http://jco.ascopubs.org/content/31/24/3004.long Barlesi et al. 2013 (AVAPERL (MO22089))]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Bevacizumab_.28Avastin.29|Bevacizumab maintenance]]
-|<span
+|style="background-color:#00cd00"|Superior PFS
-style="background:#00cd00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Superior PFS</span>
 |-
 |}
@@ Line 2,685: / Line 2,443: @@
 |-
 |[http://jco.ascopubs.org/content/31/34/4349.long Patel et al. 2013 (PointBreak)]
-|<span
+|style="background-color:#eeee00"|Non-randomized portion of RCT
-style="background:#eeee00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Non-randomized</span>
 |-
 |}
@@ Line 2,706: / Line 2,459: @@
 ===References===
-# Barlesi F, Scherpereel A, Rittmeyer A, Pazzola A, Ferrer Tur N, Kim JH, Ahn MJ, Aerts JG, Gorbunova V, Vikström A, Wong EK, Perez-Moreno P, Mitchell L, Groen HJ. Randomized Phase III Trial of Maintenance Bevacizumab With or Without Pemetrexed After First-Line Induction With Bevacizumab, Cisplatin, and Pemetrexed in Advanced Nonsquamous Non-Small-Cell Lung Cancer: AVAPERL (MO22089). J Clin Oncol. 2013 Aug 20;31(24):3004-11. Epub 2013 Jul 8. [http://jco.ascopubs.org/content/31/24/3004.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23835708 PubMed]
+# Barlesi F, Scherpereel A, Rittmeyer A, Pazzola A, Ferrer Tur N, Kim JH, Ahn MJ, Aerts JG, Gorbunova V, Vikström A, Wong EK, Perez-Moreno P, Mitchell L, Groen HJ. Randomized Phase III Trial of Maintenance Bevacizumab With or Without Pemetrexed After First-Line Induction With Bevacizumab, Cisplatin, and Pemetrexed in Advanced Nonsquamous Non-Small-Cell Lung Cancer: AVAPERL (MO22089). J Clin Oncol. 2013 Aug 20;31(24):3004-11. Epub 2013 Jul 8. [http://jco.ascopubs.org/content/31/24/3004.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23835708 PubMed]
-# Patel JD, Socinski MA, Garon EB, Reynolds CH, Spigel DR, Olsen MR, Hermann RC, Jotte RM, Beck T, Richards DA, Guba SC, Liu J, Frimodt-Moller B, John WJ, Obasaju CK, Pennella EJ, Bonomi P, Govindan R. PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. J Clin Oncol. 2013 Dec 1;31(34):4349-57. [http://jco.ascopubs.org/content/31/34/4349.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/24145346 PubMed]
+<!-- Presented in part at the Chicago Multidisciplinary Symposium in Thoracic Oncology, Chicago, IL, September 6-8, 2012, and at the American Society of Clinical Oncology's Quality Care Symposium, San Diego, CA, November 30-December 1, 2012. -->
+# Patel JD, Socinski MA, Garon EB, Reynolds CH, Spigel DR, Olsen MR, Hermann RC, Jotte RM, Beck T, Richards DA, Guba SC, Liu J, Frimodt-Moller B, John WJ, Obasaju CK, Pennella EJ, Bonomi P, Govindan R. PointBreak: a randomized phase III study of pemetrexed plus carboplatin and bevacizumab followed by maintenance pemetrexed and bevacizumab versus paclitaxel plus carboplatin and bevacizumab followed by maintenance bevacizumab in patients with stage IIIB or IV nonsquamous non-small-cell lung cancer. J Clin Oncol. 2013 Dec 1;31(34):4349-57. [http://jco.ascopubs.org/content/31/34/4349.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24145346 PubMed]
 ==Ipilimumab (Yervoy) {{#subobject:b19c3f|Regimen=1}}==
@@ Line 2,720: / Line 2,474: @@
 |-
 |[http://jco.ascopubs.org/content/30/17/2046.long Lynch et al. 2012]
-|<span
+|style="background-color:#eeee00"|Non-randomized portion of RCT
-style="background:#eeee00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Non-randomized</span>
 |-
 |}
@@ Line 2,736: / Line 2,485: @@
 ===References===
-# Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012 Jun 10;30(17):2046-54. Epub 2012 Apr 30. [http://jco.ascopubs.org/content/30/17/2046.long link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22547592 PubMed]
+<!-- Presented in part at The Chicago Multidisciplinary Symposium in Thoracic Oncology, Chicago, IL, December 9-11, 2010, and the 14th World Congress on Lung Cancer, Amsterdam, the Netherlands, July 3-7, 2011. -->
+# Lynch TJ, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Neal J, Lu H, Cuillerot JM, Reck M. Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non-small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. J Clin Oncol. 2012 Jun 10;30(17):2046-54. Epub 2012 Apr 30. [http://jco.ascopubs.org/content/30/17/2046.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22547592 PubMed]
 ==Necitumumab (Portrazza) {{#subobject:027384|Regimen=1}}==
@@ Line 2,748: / Line 2,498: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00021-2/abstract Thatcher et al. 2015 (SQUIRE)]
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00021-2/fulltext Thatcher et al. 2015 (SQUIRE)]
-|<span
+|style="background-color:#eeee00"|Non-randomized portion of RCT
-style="background:#eeee00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Non-randomized</span>
 |-
 |}
 ''Patients had stage IV squamous non-small-cell lung cancer; treatment preceded by [[#Cisplatin.2C_Gemcitabine.2C_Necitumumab|Cisplatin, Gemcitabine, Necitumumab]] x 6.''
@@ Line 2,766: / Line 2,510: @@
 ===References===
-# Thatcher N, Hirsch FR, Luft AV, Szczesna A, Ciuleanu TE, Dediu M, Ramlau R, Galiulin RK, Bálint B, Losonczy G, Kazarnowicz A, Park K, Schumann C, Reck M, Depenbrock H, Nanda S, Kruljac-Letunic A, Kurek R, Paz-Ares L, Socinski MA; SQUIRE Investigators. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2015 Jul;16(7):763-74. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00021-2/abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/26045340 PubMed]
+# Thatcher N, Hirsch FR, Luft AV, Szczesna A, Ciuleanu TE, Dediu M, Ramlau R, Galiulin RK, Bálint B, Losonczy G, Kazarnowicz A, Park K, Schumann C, Reck M, Depenbrock H, Nanda S, Kruljac-Letunic A, Kurek R, Paz-Ares L, Socinski MA; SQUIRE Investigators. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2015 Jul;16(7):763-74. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00021-2/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26045340 PubMed]
 ==Pemetrexed (Alimta) {{#subobject:ed7aa9|Regimen=1}}==
@@ Line 2,781: / Line 2,525: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.sciencedirect.com/science/article/pii/S1470204512700633 Paz-Ares et al. 2012 (PARAMOUNT)]
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70063-3/fulltext Paz-Ares et al. 2012 (PARAMOUNT)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[Non-small_cell_lung_cancer#Placebo_.28Observation.29_3|Placebo]]
+|style="background-color:#00cd00"|Superior PFS
 |-
 |}
 ''Treatment preceded by 4 cycles of induction therapy with [[#Cisplatin_.26_Pemetrexed_2 | cisplatin & pemetrexed]]. Maintenance therapy started 21 to 42 days after cycle 4 day 1 of induction chemotherapy.''
 ====Chemotherapy====
@@ Line 2,804: / Line 2,544: @@
 ===References===
-# Paz-Ares L, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2012 Mar;13(3):247-55. Epub 2012 Feb 16. [http://www.sciencedirect.com/science/article/pii/S1470204512700633 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22341744 PubMed]
+# Paz-Ares L, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2012 Mar;13(3):247-55. Epub 2012 Feb 16. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70063-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22341744 PubMed]
-## '''Update:''' Paz-Ares LG, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. PARAMOUNT: Final Overall Survival Results of the Phase III Study of Maintenance Pemetrexed Versus Placebo Immediately After Induction Treatment With Pemetrexed Plus Cisplatin for Advanced Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2013 Aug 10;31(23):2895-902. Epub 2013 Jul 8. [http://jco.ascopubs.org/content/early/2013/07/03/JCO.2012.47.1102.abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23835707 PubMed]
+## '''Update:''' Paz-Ares LG, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. PARAMOUNT: Final Overall Survival Results of the Phase III Study of Maintenance Pemetrexed Versus Placebo Immediately After Induction Treatment With Pemetrexed Plus Cisplatin for Advanced Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2013 Aug 10;31(23):2895-902. Epub 2013 Jul 8. [http://jco.ascopubs.org/content/early/2013/07/03/JCO.2012.47.1102.abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23835707 PubMed]
 ==Placebo (Observation) {{#subobject:81abec|Regimen=1}}==
@@ Line 2,818: / Line 2,558: @@
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.sciencedirect.com/science/article/pii/S1470204512700633 Paz-Ares et al. 2012 (PARAMOUNT)]
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70063-3/fulltext Paz-Ares et al. 2012 (PARAMOUNT)]
-|<span
+|style="background-color:#00cd00"|Phase III
-style="background:#00CD00;
-padding:3px 6px 3px 6px;
-border-color:black;
-border-width:2px;
-border-style:solid;">Phase III</span>
 |[[#Pemetrexed_.28Alimta.29_2|Pemetrexed]]
+|style="background-color:#ff0000"|Inferior PFS
 |-
 |}
@@ Line 2,833: / Line 2,570: @@
 ===References===
-# Paz-Ares L, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2012 Mar;13(3):247-55. Epub 2012 Feb 16. [http://www.sciencedirect.com/science/article/pii/S1470204512700633 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/22341744 PubMed]
+# Paz-Ares L, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol. 2012 Mar;13(3):247-55. Epub 2012 Feb 16. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70063-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22341744 PubMed]
-## '''Update:''' Paz-Ares LG, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. PARAMOUNT: Final Overall Survival Results of the Phase III Study of Maintenance Pemetrexed Versus Placebo Immediately After Induction Treatment With Pemetrexed Plus Cisplatin for Advanced Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2013 Aug 10;31(23):2895-902. Epub 2013 Jul 8. [http://jco.ascopubs.org/content/early/2013/07/03/JCO.2012.47.1102.abstract link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/23835707 PubMed]
+## '''Update:''' Paz-Ares LG, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C. PARAMOUNT: Final Overall Survival Results of the Phase III Study of Maintenance Pemetrexed Versus Placebo Immediately After Induction Treatment With Pemetrexed Plus Cisplatin for Advanced Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2013 Aug 10;31(23):2895-902. Epub 2013 Jul 8. [http://jco.ascopubs.org/content/early/2013/07/03/JCO.2012.47.1102.abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23835707 PubMed]
 [[Category:Chemotherapy regimens]]
 [[Category:Solid oncology regimens]]

Difference between revisions of "Non-small cell lung cancer"

Revision as of 18:33, 18 October 2016

Adjuvant therapy

Carboplatin & Paclitaxel

Regimen

Chemotherapy

References

Cisplatin & Docetaxel

Example orders

Regimen

Chemotherapy

References

Cisplatin & Etoposide

Regimen

Chemotherapy

References

Cisplatin & Gemcitabine

Regimen

Chemotherapy

References

Cisplatin & Pemetrexed

Regimen

Chemotherapy

References

Cisplatin & Vinblastine

Regimen

Chemotherapy

References

Cisplatin & Vindesine

Regimen

Chemotherapy

References

Cisplatin & Vinorelbine

Regimen #1

Chemotherapy

Regimen #2

Chemotherapy

Regimen #3

Chemotherapy

References

Placebo (Observation)

Regimen

References

Chemotherapy & radiation therapy

Carboplatin, Paclitaxel, concurrent RT

Regimen

Chemotherapy

Concurrent radiation therapy

References

Carboplatin, Paclitaxel, concurrent RT -> consolidation chemo

Regimen

Chemoradiotherapy

Concurrent radiation therapy

Consolidation chemotherapy

References

Carboplatin, Paclitaxel -> sequential RT

Regimen

Chemotherapy

Radiation therapy

References

Cisplatin, Etoposide, concurrent RT

Regimen #1

Chemoradiotherapy

Regimen #2

Chemoradiotherapy

References

Cisplatin, Etoposide, concurrent RT -> consolidation chemo

Regimen

Chemoradiotherapy

Consolidation chemotherapy

References

Cisplatin, Vinblastine, concurrent RT

Regimen

Chemoradiotherapy

References

Cisplatin, Vinblastine, sequential RT

Regimen

Chemotherapy

References

Advanced or metastatic disease, ALK-positive