Non-small cell lung cancer - historical

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the NCCN Guidelines. Is there a regimen missing from this list? See the main NSCLC page for current regimens.

11 regimens on this page
12 variants on this page


Neoadjuvant therapy

MIC

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MIC: Mitomycin, Ifosfamide, Cisplatin

Regimen

Study Evidence Comparator Efficacy
Rosell et al. 1994 Phase III (E) No preoperative therapy Superior OS

Chemotherapy

Subsequent treatment

References

  1. Rosell R, Gómez-Codina J, Camps C, Maestre J, Padille J, Cantó A, Mate JL, Li S, Roig J, Olazábal A, Canela M, Ariza A, Skacel Z, Morera-Prat J, Abad A. A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N Engl J Med. 1994 Jan 20;330(3):153-8. link to original article PubMed

Adjuvant therapy

Radiation therapy

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RT: Radiation Therapy

Regimen

Study Evidence Comparator Efficacy
Keller et al. 2000 (ECOG E3590) Phase III (C) Cisplatin, Etoposide, RT Seems not superior

Preceding treatment

Chemoradiotherapy

5-week course

References

  1. ECOG E3590: Keller SM, Adak S, Wagner H, Herskovic A, Komaki R, Brooks BJ, Perry MC, Livingston RB, Johnson DH; Eastern Cooperative Oncology Group. A randomized trial of postoperative adjuvant therapy in patients with completely resected stage II or IIIA non-small-cell lung cancer. N Engl J Med. 2000 Oct 26;343(17):1217-22. link to original article contains protocol PubMed

Definitive therapy for locally advanced disease

MVP & RT

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MVP & RT: Mitomycin, Vindesine, Platinol (Cisplatin), Radiation Therapy

Regimen

Study Evidence Comparator Efficacy
Furuse et al. 1999 Phase III (E) MVP, then RT Seems to have superior OS

Chemotherapy

References

  1. Furuse K, Fukuoka M, Kawahara M, Nishikawa H, Takada Y, Kudoh S, Katagami N, Ariyoshi Y. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol. 1999 Sep;17(9):2692-9. link to original article PubMed

Advanced or metastatic disease, first-line

Best supportive care

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Regimen

Study Evidence Comparator Efficacy
Rapp et al. 1988 Phase III (C) Cisplatin & Vindesine Inferior OS
Cullen et al. 1999 (MIC2) Phase III (C) MIC Seems to have inferior OS
Ranson et al. 2000 Phase III (C) Paclitaxel Seems to have inferior OS

No active antineoplastic treatment.

References

  1. Rapp E, Pater JL, Willan A, Cormier Y, Murray N, Evans WK, Hodson DI, Clark DA, Feld R, Arnold AM, Ayoub JI, Wilson KS, Latreille J, Wierzbicki RF, Hill DP. Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer--report of a Canadian multicenter randomized trial. J Clin Oncol. 1988 Apr;6(4):633-41. link to original article PubMed
  2. Cullen MH, Billingham LJ, Woodroffe CM, Chetiyawardana AD, Gower NH, Joshi R, Ferry DR, Rudd RM, Spiro SG, Cook JE, Trask C, Bessell E, Connolly CK, Tobias J, Souhami RL. Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life. J Clin Oncol. 1999 Oct;17(10):3188-94. link to original article PubMed
  3. Ranson M, Davidson N, Nicolson M, Falk S, Carmichael J, Lopez P, Anderson H, Gustafson N, Jeynes A, Gallant G, Washington T, Thatcher N. Randomized trial of paclitaxel plus supportive care versus supportive care for patients with advanced non-small-cell lung cancer. J Natl Cancer Inst. 2000 Jul 5;92(13):1074-80. link to original article PubMed

Cisplatin & Pemetrexed

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Pem-Cis: Pemetrexed & Cisplatin
Cis-Pem: Cisplatin & Pemetrexed

Regimen

Study Evidence Comparator Efficacy
Scagliotti et al. 2008 (JMDB) Phase III (E) Cisplatin & Gemcitabine Seems non-inferior

Note: although this regimen is still current for nonsquamous NSCLC, the JMDB trial was unselected by histology.

Chemotherapy

Supportive medications

21-day cycle for 4 to 6 cycles

References

  1. JMDB: 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

Cisplatin & Vindesine

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VP: Vindesine & Platinol (Cisplatin)

Regimen

Study Evidence Comparator Efficacy
Ruckdeschel et al. 1986 (ECOG E1581) Phase III (E) 1. CAMP
2. EC
3. MVP
Seems not superior
Rapp et al. 1988 Phase III (E) Best supportive care Superior OS
Vansteenkiste et al. 2001 Phase III (C) Gemcitabine Seems to have inferior clinical benefit
Negoro et al. 2003 Phase III (C) Cisplatin & Irinotecan Seems not superior

Chemotherapy

References

  1. ECOG E1581: Ruckdeschel JC, Finkelstein DM, Ettinger DS, Creech RH, Mason BA, Joss RA, Vogl S. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol. 1986 Jan;4(1):14-22. link to original article PubMed
  2. Rapp E, Pater JL, Willan A, Cormier Y, Murray N, Evans WK, Hodson DI, Clark DA, Feld R, Arnold AM, Ayoub JI, Wilson KS, Latreille J, Wierzbicki RF, Hill DP. Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer--report of a Canadian multicenter randomized trial. J Clin Oncol. 1988 Apr;6(4):633-41. link to original article PubMed
  3. Vansteenkiste JF, Vandebroek JE, Nackaerts KL, Weynants P, Valcke YJ, Verresen DA, Devogelaere RC, Marien SA, Humblet YP, Dams NL; Leuven Lung Cancer Group. Clinical-benefit response in advanced non-small-cell lung cancer: a multicentre prospective randomised phase III study of single agent gemcitabine versus cisplatin-vindesine. Ann Oncol. 2001 Sep;12(9):1221-30. link to original article PubMed
  4. Negoro S, Masuda N, Takada Y, Sugiura T, Kudoh S, Katakami N, Ariyoshi Y, Ohashi Y, Niitani H, Fukuoka M; CPT-11 Lung Cancer Study Group West. Randomised phase III trial of irinotecan combined with cisplatin for advanced non-small-cell lung cancer. Br J Cancer. 2003 Feb 10;88(3):335-41. link to original article link to PMC article contains verified protocol PubMed

Docetaxel & Gemcitabine

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DG: Docetaxel & Gemcitabine

Regimen

Study Evidence Comparator Efficacy
Georgoulias et al. 2007 Phase III (E) Docetaxel Seems to have superior OS

Note: while this is a superior arm of a phase III RCT, the comparator (single-agent docetaxel) is not usually used in the first-line treatment and this regimen is not currently recommended by ESMO guidelines.

Chemotherapy

References

  1. Georgoulias V, Androulakis N, Kotsakis A, Hatzidaki D, Syrigos K, Polyzos A, Agelidou A, Varthalitis I, Ziras N, Agelidou M, Chandrinos V, Boukovinas I, Geroyianni A, Vamvakas L, Mavroudis D. Docetaxel versus docetaxel plus gemcitabine as front-line treatment of patients with advanced non-small cell lung cancer: a randomized, multicenter phase III trial. Lung Cancer. 2008 Jan;59(1):57-63. Epub 2007 Aug 31. link to SD article PubMed

MACC

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MACC: Methotrexate, Adriamycin (Doxorubicin), Cyclophosphamide, CCNU (Lomustine)

Regimen

Study Evidence Comparator Efficacy
Cormier et al. 1982 Phase III (E) Placebo Superior OS

Chemotherapy

References

  1. Cormier Y, Bergeron D, La Forge J, Lavandier M, Fournier M, Chenard J, Desmeules M. Benefits of polychemotherapy in advanced non-small-cell bronchogenic carcinoma. Cancer. 1982 Sep 1;50(5):845-9. link to original article PubMed

MIC

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MIC: Mitomycin, Ifosfamide, Cisplatin

Regimen

Study Evidence Comparator Efficacy
Cullen et al. 1999 (MIC2) Phase III (E) Best supportive care Seems to have superior OS
Danson et al. 2003 Phase III (C) GC Seems not superior
Booton et al. 2006 (BTOG1) Phase III (C) DCb Seems not superior

Chemotherapy

References

  1. Cullen MH, Billingham LJ, Woodroffe CM, Chetiyawardana AD, Gower NH, Joshi R, Ferry DR, Rudd RM, Spiro SG, Cook JE, Trask C, Bessell E, Connolly CK, Tobias J, Souhami RL. Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life. J Clin Oncol. 1999 Oct;17(10):3188-94. link to original article PubMed
  2. Danson S, Middleton MR, O'Byrne KJ, Clemons M, Ranson M, Hassan J, Anderson H, Burt PA, Fairve-Finn C, Stout R, Dowd I, Ashcroft L, Beresford C, Thatcher N. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer. 2003 Aug 1;98(3):542-53. link to original article PubMed
  3. Booton R, Lorigan P, Anderson H, Baka S, Ashcroft L, Nicolson M, O'Brien M, Dunlop D, O'Byrne K, Laurence V, Snee M, Dark G, Thatcher N. A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1). Ann Oncol. 2006 Jul;17(7):1111-9. Epub 2006 Apr 7. link to original article PubMed

MVP

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MVP: Mitomycin, Vinblastine, Platinol (Cisplatin)

Regimen

Study Evidence Comparator Efficacy
Ruckdeschel et al. 1986 (ECOG E1581) Phase III (E) 1. CAMP
2. EC
3. VC
Seems not superior
Smith et al. 2001 Phase III (C) MVP x 3 Seems not superior
Danson et al. 2003 Phase III (C) GC Seems not superior
Booton et al. 2006 (BTOG1) Phase III (C) DCb Seems not superior

Chemotherapy

References

  1. ECOG E1581: Ruckdeschel JC, Finkelstein DM, Ettinger DS, Creech RH, Mason BA, Joss RA, Vogl S. A randomized trial of the four most active regimens for metastatic non-small-cell lung cancer. J Clin Oncol. 1986 Jan;4(1):14-22. link to original article PubMed
  2. Smith IE, O'Brien ME, Talbot DC, Nicolson MC, Mansi JL, Hickish TF, Norton A, Ashley S. Duration of chemotherapy in advanced non-small-cell lung cancer: a randomized trial of three versus six courses of mitomycin, vinblastine, and cisplatin. J Clin Oncol. 2001 Mar 1;19(5):1336-43. link to original article PubMed
  3. Danson S, Middleton MR, O'Byrne KJ, Clemons M, Ranson M, Hassan J, Anderson H, Burt PA, Fairve-Finn C, Stout R, Dowd I, Ashcroft L, Beresford C, Thatcher N. Phase III trial of gemcitabine and carboplatin versus mitomycin, ifosfamide, and cisplatin or mitomycin, vinblastine, and cisplatin in patients with advanced nonsmall cell lung carcinoma. Cancer. 2003 Aug 1;98(3):542-53. link to original article PubMed
  4. BTOG1: Booton R, Lorigan P, Anderson H, Baka S, Ashcroft L, Nicolson M, O'Brien M, Dunlop D, O'Byrne K, Laurence V, Snee M, Dark G, Thatcher N. A phase III trial of docetaxel/carboplatin versus mitomycin C/ifosfamide/cisplatin (MIC) or mitomycin C/vinblastine/cisplatin (MVP) in patients with advanced non-small-cell lung cancer: a randomised multicentre trial of the British Thoracic Oncology Group (BTOG1). Ann Oncol. 2006 Jul;17(7):1111-9. Epub 2006 Apr 7. link to original article PubMed

Paclitaxel monotherapy

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Variant #1, 100 mg/m2, 3 out of 4 weeks

Study Evidence Comparator Efficacy
Comella et al. 2004 (SICOG 9909) Phase III (E) 1. Gemcitabine Not reported
2. GT
3. GV
Seems to have inferior OS

Chemotherapy

28-day cycle for up to 6 cycles

Variant #2, 200 mg/m2 q3wk

Study Evidence Comparator Efficacy
Ranson et al. 2000 Phase III (E) Best supportive care Seems to have superior OS

Chemotherapy

21-day cycles

References

  1. Ranson M, Davidson N, Nicolson M, Falk S, Carmichael J, Lopez P, Anderson H, Gustafson N, Jeynes A, Gallant G, Washington T, Thatcher N. Randomized trial of paclitaxel plus supportive care versus supportive care for patients with advanced non-small-cell lung cancer. J Natl Cancer Inst. 2000 Jul 5;92(13):1074-80. link to original article PubMed
  2. SICOG 9909: Comella P, Frasci G, Carnicelli P, Massidda B, Buzzi F, Filippelli G, Maiorino L, Guida M, Panza N, Mancarella S, Cioffi R. Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients. Br J Cancer. 2004 Aug 2;91(3):489-97. link to original article link to PMC article contains verified protocol PubMed

Placebo

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Regimen

Study Evidence Comparator Efficacy
Cormier et al. 1982 Phase III (C) MACC Inferior OS

No active antineoplastic treatment.

References

  1. Cormier Y, Bergeron D, La Forge J, Lavandier M, Fournier M, Chenard J, Desmeules M. Benefits of polychemotherapy in advanced non-small-cell bronchogenic carcinoma. Cancer. 1982 Sep 1;50(5):845-9. link to original article PubMed

Maintenance after first-line therapy

Erlotinib monotherapy

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Regimen

Study Evidence Comparator Efficacy
Cappuzzo et al. 2010 (SATURN) Phase III (E) Placebo Superior PFS
Pérol et al. 2012 Phase III (E) 1. Gemcitabine Not reported
2. Observation Superior PFS
Cicènas et al. 2016 (IUNO) Phase III (E) See link See link

Note: while SATURN was technically a positive study for erlotinib, the median PFS gain was 1.2 weeks. The trials included here did not require EGFR mutation as a condition for enrollment.

Preceding treatment

Chemotherapy

Continued indefinitely

References

  1. SATURN: Cappuzzo F, Ciuleanu T, Stelmakh L, Cicenas S, Szczésna A, Juhász E, Esteban E, Molinier O, Brugger W, Melezínek I, Klingelschmitt G, Klughammer B, Giaccone G; SATURN investigators. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2010 Jun;11(6):521-9. Epub 2010 May 20. link to original article contains protocol PubMed
  2. Pérol M, Chouaid C, Pérol D, Barlési F, Gervais R, Westeel V, Crequit J, Léna H, Vergnenègre A, Zalcman G, Monnet I, Le Caer H, Fournel P, Falchero L, Poudenx M, Vaylet F, Ségura-Ferlay C, Devouassoux-Shisheboran M, Taron M, Milleron B. Randomized, phase III study of gemcitabine or erlotinib maintenance therapy versus observation, with predefined second-line treatment, after cisplatin-gemcitabine induction chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol. 2012 Oct 1;30(28):3516-24. Epub 2012 Sep 4. link to original article contains verified protocol PubMed
  3. IUNO: Cicènas S, Geater SL, Petrov P, Hotko Y, Hooper G, Xia F, Mudie N, Wu YL. Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study). Lung Cancer. 2016 Dec;102:30-37. Epub 2016 Oct 20. link to original article contains verified protocol PubMed

Advanced or metastatic disease, subsequent lines of therapy

Erlotinib monotherapy

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Regimen

Study Evidence Comparator Efficacy
Shepherd et al. 2005 (NCIC CTG BR.21) Phase III (E) Placebo Superior OS
Natale et al. 2011 (ZEST) Phase III (C) Vandetanib Seems not superior
Herbst et al. 2011 (BeTa) Phase III (C) Erlotinib & Bevacizumab Seems not superior
Ciuleanu et al. 2012 (TITAN) Phase III (E) Investigator's choice of:
1. Docetaxel
2. Pemetrexed
Seems not superior
Scagliotti et al. 2012 (SUN 1087) Phase III (C) Erlotinib & Sunitinib Seems not superior
Ramalingam et al. 2012 (A7471028) Randomized Phase II (C) Dacomitinib Seems to have inferior PFS
Karampeazis et al. 2013 Phase III (E) Pemetrexed Seems not superior
Garassino et al. 2013 (TAILOR-NSCLC) Phase III (E) Docetaxel Seems to have inferior OS
Kawaguchi et al. 2014 (DELTA) Phase III (E) Docetaxel Might have inferior PFS
Ramalingam et al. 2014 (ARCHER 1009) Phase III (C) Dacomitinib Seems not superior
Scagliotti et al. 2015 (ADVIGO 1018) Phase III (C) Erlotinib & Figitumumab Seems not superior
Soria et al. 2015 (LUX-Lung 8) Phase III (C) Afatinib Inferior OS
Yoshioka et al. 2015 (ATTENTION) Phase III (C) Erlotinib & Tivantinib Seems not superior
Scagliotti et al. 2015 (ARQ197-A-U302) Phase III (C) Erlotinib & Tivantinib Seems not superior
Urata et al. 2016 (WJOG 5108L) Phase III (C) Gefitinib Inconclusive whether non-inferior
Smit et al. 2016 (CurrentS) Phase III (C) High-dose Erlotinib Seems not superior
Cicènas et al. 2016 (IUNO) Phase III (C) See link See link
Neal et al. 2016 (ECOG-ACRIN 1512) Randomized Phase II (C) 1. Cabozantinib Inferior PFS
2. Cabozantinib & Erlotinib Inferior PFS
Spigel et al. 2016 (METLung) Phase III (C) Erlotinib & Onartuzumab Might have superior OS

Note: the trials included here did not require EGFR mutation as a condition for enrollment. Given the FDA limitation on use in this setting, these regimens have been moved to the historical page. Note that there is another trial named TAILOR in colorectal cancer, so this one has been dubbed TAILOR-NSCLC.

Preceding treatment

Chemotherapy

Continued indefinitely

References

  1. NCIC CTG BR.21: 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
  2. ZEST: Natale RB, Thongprasert S, Greco FA, Thomas M, Tsai CM, Sunpaweravong P, Ferry D, Mulatero C, Whorf R, Thompson J, Barlesi F, Langmuir P, Gogov S, Rowbottom JA, Goss GD. Phase III trial of vandetanib compared with erlotinib in patients with previously treated advanced non-small-cell lung cancer. J Clin Oncol. 2011 Mar 10;29(8):1059-66. Epub 2011 Jan 31. link to original article contains protocol PubMed
    1. Dataset: Project Data Sphere
  3. BeTa: Herbst RS, Ansari R, Bustin F, Flynn P, Hart L, Otterson GA, Vlahovic G, Soh CH, O'Connor P, Hainsworth J. Efficacy of bevacizumab plus erlotinib versus erlotinib alone in advanced non-small-cell lung cancer after failure of standard first-line chemotherapy (BeTa): a double-blind, placebo-controlled, phase 3 trial. Lancet. 2011 May 28;377(9780):1846-54. link to original article link to PMC article contains protocol PubMed
  4. TITAN: Ciuleanu T, Stelmakh L, Cicenas S, Miliauskas S, Grigorescu AC, Hillenbach C, Johannsdottir HK, Klughammer B, Gonzalez EE. Efficacy and safety of erlotinib versus chemotherapy in second-line treatment of patients with advanced, non-small-cell lung cancer with poor prognosis (TITAN): a randomised multicentre, open-label, phase 3 study. Lancet Oncol. 2012 Mar;13(3):300-8. Epub 2012 Jan 24. link to original article PubMed
  5. SUN 1087: Scagliotti GV, Krzakowski M, Szczesna A, Strausz J, Makhson A, Reck M, Wierzbicki RF, Albert I, Thomas M, Miziara JE, Papai ZS, Karaseva N, Thongprasert S, Portulas ED, von Pawel J, Zhang K, Selaru P, Tye L, Chao RC, Govindan R. Sunitinib plus erlotinib versus placebo plus erlotinib in patients with previously treated advanced non-small-cell lung cancer: a phase III trial. J Clin Oncol. 2012 Jun 10;30(17):2070-8. Epub 2012 May 7. link to original article contains protocol PubMed
  6. A7471028: Ramalingam SS, Blackhall F, Krzakowski M, Barrios CH, Park K, Bover I, Seog Heo D, Rosell R, Talbot DC, Frank R, Letrent SP, Ruiz-Garcia A, Taylor I, Liang JQ, Campbell AK, O'Connell J, Boyer M. Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2012 Sep 20;30(27):3337-44. link to original article link to PMC article PubMed
  7. Karampeazis A, Voutsina A, Souglakos J, Kentepozidis N, Giassas S, Christofillakis C, Kotsakis A, Papakotoulas P, Rapti A, Agelidou M, Agelaki S, Vamvakas L, Samonis G, Mavroudis D, Georgoulias V. Pemetrexed versus erlotinib in pretreated patients with advanced non-small cell lung cancer: a Hellenic Oncology Research Group (HORG) randomized phase 3 study. Cancer. 2013 Aug 1;119(15):2754-64. Epub 2013 May 9. link to original article contains verified protocol PubMed
  8. TAILOR-NSCLC: Garassino MC, Martelli O, Broggini M, Farina G, Veronese S, Rulli E, Bianchi F, Bettini A, Longo F, Moscetti L, Tomirotti M, Marabese M, Ganzinelli M, Lauricella C, Labianca R, Floriani I, Giaccone G, Torri V, Scanni A, Marsoni S; TAILOR trialists. Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial. Lancet Oncol. 2013 Sep;14(10):981-8. Epub 2013 Jul 22. link to original article contains verified protocol PubMed
  9. DELTA: Kawaguchi T, Ando M, Asami K, Okano Y, Fukuda M, Nakagawa H, Ibata H, Kozuki T, Endo T, Tamura A, Kamimura M, Sakamoto K, Yoshimi M, Soejima Y, Tomizawa Y, Isa S, Takada M, Saka H, Kubo A. Randomized phase III trial of erlotinib versus docetaxel as second- or third-line therapy in patients with advanced non-small-cell lung cancer: Docetaxel and Erlotinib Lung Cancer Trial (DELTA). J Clin Oncol. 2014 Jun 20;32(18):1902-8. Epub 2014 May 19. link to original article contains verified protocol PubMed
  10. ARCHER 1009: Ramalingam SS, Jänne PA, Mok T, O'Byrne K, Boyer MJ, Von Pawel J, Pluzanski A, Shtivelband M, Docampo LI, Bennouna J, Zhang H, Liang JQ, Doherty JP, Taylor I, Mather CB, Goldberg Z, O'Connell J, Paz-Ares L. Dacomitinib versus erlotinib in patients with advanced-stage, previously treated non-small-cell lung cancer (ARCHER 1009): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1369-78. Epub 2014 Oct 15.link to original article PubMed
  11. ADVIGO 1018: 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
  12. LUX-Lung 8: 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
  13. ATTENTION: Yoshioka H, Azuma K, Yamamoto N, Takahashi T, Nishio M, Katakami N, Ahn MJ, Hirashima T, Maemondo M, Kim SW, Kurosaki M, Akinaga S, Park K, Tsai CM, Tamura T, Mitsudomi T, Nakagawa K. A randomized, double-blind, placebo-controlled, phase III trial of erlotinib with or without a c-Met inhibitor tivantinib (ARQ 197) in Asian patients with previously treated stage IIIB/IV nonsquamous nonsmall-cell lung cancer harboring wild-type epidermal growth factor receptor (ATTENTION study). Ann Oncol. 2015 Oct;26(10):2066-72. Epub 2015 Jul 7. link to original article PubMed
  14. ARQ197-A-U302: Scagliotti G, von Pawel J, Novello S, Ramlau R, Favaretto A, Barlesi F, Akerley W, Orlov S, Santoro A, Spigel D, Hirsh V, Shepherd FA, Sequist LV, Sandler A, Ross JS, Wang Q, von Roemeling R, Shuster D, Schwartz B. Phase III multinational, randomized, double-blind, placebo-controlled study of tivantinib (ARQ 197) plus erlotinib versus erlotinib alone in previously treated patients with locally advanced or metastatic nonsquamous non-small-cell lung cancer. J Clin Oncol. 2015 Aug 20;33(24):2667-74. Epub 2015 Jul 13. link to original article contains protocol PubMed
  15. WJOG 5108L: 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
  16. CurrentS: Smit EF, Wu YL, Gervais R, Zhou C, Felip E, Feng J, Guclu SZ, Hoiczyk M, Dorokhova E, Freudensprung U, Grange S, Perez-Moreno PD, Mitchell L, Reck M. A randomized, double-blind, phase III study comparing two doses of erlotinib for second-line treatment of current smokers with advanced non-small-cell lung cancer (CurrentS). Lung Cancer. 2016 Sep;99:94-101. Epub 2016 Jun 27. link to original article PubMed
  17. IUNO: Cicènas S, Geater SL, Petrov P, Hotko Y, Hooper G, Xia F, Mudie N, Wu YL. Maintenance erlotinib versus erlotinib at disease progression in patients with advanced non-small-cell lung cancer who have not progressed following platinum-based chemotherapy (IUNO study). Lung Cancer. 2016 Dec;102:30-37. Epub 2016 Oct 20. link to original article contains verified protocol PubMed
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