|
|
| (107 intermediate revisions by 2 users not shown) |
| Line 1: |
Line 1: |
| − | <span id="BackToTop"></span>
| + | ==Carboplatin & Paclitaxel (CP) & Nivolumab {{#subobject:3a6hg7|Regimen=1}}== |
| − | <div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px">
| + | CP & Nivolumab: '''<u>C</u>'''arboplatin, '''<u>P</u>'''aclitaxel, Nivolumab |
| − | [[#top|Back to Top]]
| + | <div class="toccolours" style="background-color:#eeeeee"> |
| − | </div>
| + | ===Regimen variant #1, 5/175/360 {{#subobject:59hhq7|Variant=1}}=== |
| − | {{#lst:Section editor transclusions|nsclc}}
| |
| − | Note: these are regimens tested in biomarker-specific populations, please see the '''[[Non-small cell lung cancer|main NSCLC page]]''' for other regimens.
| |
| − | {| class="wikitable" style="float:right; margin-right: 5px;"
| |
| − | |-
| |
| − | |<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
| |
| − | <div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
| |
| − | |}
| |
| − | {{TOC limit|limit=3}}
| |
| − | =Advanced or metastatic disease, ALK inhibitor-naive=
| |
| − | | |
| − | ==Alectinib monotherapy {{#subobject:b1194c|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen variant #1, 300 mg twice per day {{#subobject:9cef11|Variant=1}}===
| |
| − | {| class="wikitable sortable" style="width: 100%; text-align:center;"
| |
| − | !style="width: 20%"|Study
| |
| − | !style="width: 20%"|Years of enrollment
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !style="width: 20%"|Comparator
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
| |
| − | |-
| |
| − | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70142-6/fulltext Seto et al. 2013 (AF-001JP)]
| |
| − | |2010-2012
| |
| − | |style="background-color:#91cf61"|Phase 1/2
| |
| − | |style="background-color:#d3d3d3"|
| |
| − | |style="background-color:#d3d3d3"|
| |
| − | |-
| |
| − | |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30565-2/fulltext Hida et al. 2017 (J-ALEX)]
| |
| − | |2013-2015
| |
| − | |style="background-color:#1a9851"|Phase 3 (E-switch-ic)
| |
| − | |[[#Crizotinib_monotherapy|Crizotinib]]
| |
| − | |style="background-color:#1a9850"|Superior PFS
| |
| − | |-
| |
| − | |}
| |
| − | ''This is the PMDA-approved dose in Japan.''
| |
| − | ====Biomarker Eligibility Criteria====
| |
| − | *Biomarker: ALK Fusion Gene Rearrangement
| |
| − | *Diagnostics: FISH or RT-PCR
| |
| − | | |
| − | ====Targeted therapy====
| |
| − | *[[Alectinib (Alecensa)]] 300 mg PO twice per day
| |
| − | | |
| − | '''Continued indefinitely'''
| |
| − | | |
| − | ===Regimen variant #2, 600 mg twice per day {{#subobject:92a408|Variant=1}}===
| |
| − | {| class="wikitable" style="color:white; background-color:#404040"
| |
| − | |<small>'''FDA-recommended dose'''</small>
| |
| − | |-
| |
| − | |}
| |
| − | {| class="wikitable sortable" style="width: 100%; text-align:center;"
| |
| − | !style="width: 20%"|Study
| |
| − | !style="width: 20%"|Years of enrollment
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !style="width: 20%"|Comparator
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
| |
| − | |-
| |
| − | |[https://www.nejm.org/doi/full/10.1056/NEJMoa1704795 Peters et al. 2017 (ALEX)]
| |
| − | |2014-2016
| |
| − | |style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic)
| |
| − | |[[#Crizotinib_monotherapy|Crizotinib]]
| |
| − | | style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup>
| |
| − | |-
| |
| − | |[https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(19)30053-0/fulltext Zhou et al. 2019 (ALESIA)]
| |
| − | |2016-2017
| |
| − | |style="background-color:#1a9851"|Phase 3 (E-switch-ic)
| |
| − | |[[#Crizotinib_monotherapy|Crizotinib]]
| |
| − | |style="background-color:#1a9850"|Superior PFS
| |
| − | |-
| |
| − | |}
| |
| − | ''<sup>1</sup>Reported efficacy for ALEX is based on the 2020 update; the authors mention that OS results are immature.''
| |
| − | ====Biomarker eligibility criteria====
| |
| − | *Biomarker: ALK Fusion Gene Rearrangement
| |
| − | *Diagnostics: IHC
| |
| − | | |
| − | ====Targeted therapy====
| |
| − | *[[Alectinib (Alecensa)]] 600 mg PO twice per day
| |
| − | | |
| − | '''Continued indefinitely'''
| |
| − | | |
| − | ===References===
| |
| − | # '''AF-001JP:''' Seto T, Kiura K, Nishio M, Nakagawa K, Maemondo M, Inoue A, Hida T, Yamamoto N, Yoshioka H, Harada M, Ohe Y, Nogami N, Takeuchi K, Shimada T, Tanaka T, Tamura T. CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): a single-arm, open-label, phase 1-2 study. Lancet Oncol. 2013 Jun;14(7):590-8. Epub 2013 Apr 30. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70142-6/fulltext link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/23639470 PubMed] JapicCTI-101264
| |
| − | ## '''Update:''' Tamura T, Kiura K, Seto T, Nakagawa K, Maemondo M, Inoue A, Hida T, Yoshioka H, Harada M, Ohe Y, Nogami N, Murakami H, Kuriki H, Shimada T, Tanaka T, Takeuchi K, Nishio M. Three-year follow-up of an alectinib phase I/II study in ALK-positive non-small-cell lung cancer: AF-001JP. J Clin Oncol. 2017 May 10;35(14):1515-1521. Epub 2017 Mar 15. [https://doi.org/10.1200/JCO.2016.70.5749 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455704/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28296581 PubMed]
| |
| − | # '''J-ALEX:''' Hida T, Nokihara H, Kondo M, Kim YH, Azuma K, Seto T, Takiguchi Y, Nishio M, Yoshioka H, Imamura F, Hotta K, Watanabe S, Goto K, Satouchi M, Kozuki T, Shukuya T, Nakagawa K, Mitsudomi T, Yamamoto N, Asakawa T, Asabe R, Tanaka T, Tamura T. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet. 2017 Jul 1;390(10089):29-39. Epub 2017 May 10. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30565-2/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/28501140 PubMed] JapicCTI-132316
| |
| − | ## '''Subgroup analysis:''' Nishio M, Nakagawa K, Mitsudomi T, Yamamoto N, Tanaka T, Kuriki H, Zeaiter A, Tamura T. Analysis of central nervous system efficacy in the J-ALEX study of alectinib versus crizotinib in ALK-positive non-small-cell lung cancer. Lung Cancer. 2018 Jul;121:37-40. Epub 2018 Apr 17. [https://doi.org/10.1016/j.lungcan.2018.04.015 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29858024 PubMed]
| |
| − | # '''ALEX:''' Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, Ou SI, Pérol M, Dziadziuszko R, Rosell R, Zeaiter A, Mitry E, Golding S, Balas B, Noe J, Morcos PN, Mok T; ALEX Trial Investigators. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017 Aug 31;377(9):829-838. Epub 2017 Jun 6. [https://www.nejm.org/doi/full/10.1056/NEJMoa1704795 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/28586279 PubMed] NCT02075840
| |
| − | ## '''Subgroup analysis:''' Gadgeel S, Peters S, Mok T, Shaw AT, Kim DW, Ou SI, Pérol M, Wrona A, Novello S, Rosell R, Zeaiter A, Liu T, Nüesch E, Balas B, Camidge DR. Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study. Ann Oncol. 2018 Nov 1;29(11):2214-2222. [https://doi.org/10.1093/annonc/mdy405 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290889/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30215676 PubMed]
| |
| − | ## '''Update:''' Camidge DR, Dziadziuszko R, Peters S, Mok T, Noe J, Nowicka M, Gadgeel SM, Cheema P, Pavlakis N, de Marinis F, Cho BC, Zhang L, Moro-Sibilot D, Liu T, Bordogna W, Balas B, Müller B, Shaw AT. Updated efficacy and safety data and impact of the EML4-ALK fusion variant on the efficacy of alectinib in untreated ALK-positive advanced non-small cell lung cancer in the global phase III ALEX study. J Thorac Oncol. 2019 Jul;14(7):1233-1243. Epub 2019 Mar 20. [https://www.jto.org/article/S1556-0864(19)30210-2/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/30902613 PubMed]
| |
| − | ## '''Update:''' Mok T, Camidge DR, Gadgeel SM, Rosell R, Dziadziuszko R, Kim DW, Pérol M, Ou SI, Ahn JS, Shaw AT, Bordogna W, Smoljanović V, Hilton M, Ruf T, Noé J, Peters S. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020 Aug;31(8):1056-1064. Epub 2020 May 11. [https://doi.org/10.1016/j.annonc.2020.04.478 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32418886 PubMed]
| |
| − | # '''ALESIA:''' Zhou C, Kim SW, Reungwetwattana T, Zhou J, Zhang Y, He J, Yang JJ, Cheng Y, Lee SH, Bu L, Xu T, Yang L, Wang C, Liu T, Morcos PN, Lu Y, Zhang L. Alectinib versus crizotinib in untreated Asian patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer (ALESIA): a randomised phase 3 study. Lancet Respir Med. 2019 May;7(5):437-446. Epub 2019 Apr 10. [https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(19)30053-0/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/30981696 PubMed] NCT02838420
| |
| − | | |
| − | ==Brigatinib monotherapy {{#subobject:93d753|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:1d93bc|Variant=1}}===
| |
| − | {| class="wikitable sortable" style="width: 100%; text-align:center;"
| |
| − | !style="width: 20%"|Study
| |
| − | !style="width: 20%"|Years of enrollment
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !style="width: 20%"|Comparator
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
| |
| − | |-
| |
| − | |[https://www.nejm.org/doi/full/10.1056/NEJMoa1810171 Camidge et al. 2018 (ALTA-1L)]
| |
| − | |2016-2017
| |
| − | |style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic)
| |
| − | |[[#Crizotinib_monotherapy|Crizotinib]]
| |
| − | | style="background-color:#1a9850" |Superior PFS<sup>1</sup><br>Median PFS: 24 vs 11.1 mo<br>(HR 0.48, 95% CI 0.35-0.66)
| |
| − | |-
| |
| − | |}
| |
| − | ''<sup>1</sup>Reported efficacy is based on the 2021 update.''
| |
| − | ====Biomarker eligibility criteria====
| |
| − | *Biomarker: ALK Fusion Gene Rearrangement
| |
| − | *Diagnostics: FISH or FDA-approved test
| |
| − | | |
| − | ====Targeted therapy====
| |
| − | *[[Brigatinib (Alunbrig)]] as follows:
| |
| − | **Lead-in: 90 mg PO once per day for 7 days
| |
| − | **Subsequently: 180 mg PO once per day
| |
| − | | |
| − | '''Continued indefinitely'''
| |
| − | ===References===
| |
| − | # '''ALTA-1L:''' Camidge DR, Kim HR, Ahn MJ, Yang JC, Han JY, Lee JS, Hochmair MJ, Li JY, Chang GC, Lee KH, Gridelli C, Delmonte A, Garcia Campelo R, Kim DW, Bearz A, Griesinger F, Morabito A, Felip E, Califano R, Ghosh S, Spira A, Gettinger SN, Tiseo M, Gupta N, Haney J, Kerstein D, Popat S. Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer. N Engl J Med. 2018 Nov 22;379(21):2027-2039. Epub 2018 Sep 25. [https://www.nejm.org/doi/full/10.1056/NEJMoa1810171 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/30280657 PubMed] NCT02737501
| |
| − | ## '''Update:''' Camidge DR, Kim HR, Ahn MJ, Yang JCH, Han JY, Hochmair MJ, Lee KH, Delmonte A, García Campelo MR, Kim DW, Griesinger F, Felip E, Califano R, Spira A, Gettinger SN, Tiseo M, Lin HM, Gupta N, Hanley MJ, Ni Q, Zhang P, Popat S. Brigatinib Versus Crizotinib in Advanced ALK Inhibitor-Naive ALK-Positive Non-Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial. J Clin Oncol. 2020 Nov 1;38(31):3592-3603. Epub 2020 Aug 11. [https://doi.org/10.1200/jco.20.00505 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605398/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32780660 PubMed]
| |
| − | ## '''Update:''' Camidge DR, Kim HR, Ahn MJ, Yang JCH, Han JY, Hochmair MJ, Lee KH, Delmonte A, Garcia Campelo MR, Kim DW, Griesinger F, Felip E, Califano R, Spira AI, Gettinger SN, Tiseo M, Lin HM, Liu Y, Vranceanu F, Niu H, Zhang P, Popat S. Brigatinib Versus Crizotinib in ALK Inhibitor-Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial. J Thorac Oncol. 2021 Dec;16(12):2091-2108. Epub 2021 Sep 16. [https://doi.org/10.1016/j.jtho.2021.07.035 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34537440/ PubMed]
| |
| − | | |
| − | ==Carboplatin & Pemetrexed {{#subobject:920f46|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | CP: '''<u>C</u>'''arboplatin & '''<u>P</u>'''emetrexed | |
| − | <br>Carbo-Pem: '''<u>Carbo</u>'''platin & '''<u>Pem</u>'''etrexed
| |
| − | ===Regimen variant #1, 5/500 x 4 {{#subobject:843af0|Variant=1}}===
| |
| − | {| class="wikitable sortable" style="width: 100%; text-align:center;"
| |
| − | !style="width: 20%"|Study
| |
| − | !style="width: 20%"|Years of enrollment
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !style="width: 20%"|Comparator
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
| |
| − | |-
| |
| − | |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30123-X/fulltext Soria et al. 2017 (ASCEND-4)]
| |
| − | |2013-2015
| |
| − | |style="background-color:#1a9851"|Phase 3 (C)
| |
| − | |[[#Ceritinib_monotherapy|Ceritinib]]
| |
| − | |style="background-color:#d73027"|Inferior PFS
| |
| − | |-
| |
| − | |}
| |
| − | ====Biomarker Eligibility Criteria====
| |
| − | *Biomarker: ALK Fusion Gene Rearrangement
| |
| − | *Diagnostics: IHC
| |
| − | | |
| − | ====Chemotherapy====
| |
| − | *[[Carboplatin (Paraplatin)]] AUC 5 IV over 15 to 60 minutes once on day 1, '''given second'''
| |
| − | *[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV over 10 minutes once on day 1, '''given first'''
| |
| − | | |
| − | ====Supportive medications====
| |
| − | *[[Dexamethasone (Decadron)]] 4 mg or [[steroid conversions|equivalent corticosteroid]] PO twice per day on the day before, the day of, and day after each dose of [[Pemetrexed (Alimta)]]
| |
| − | *[[Folic acid (Folate)]] 350 to 600 mcg PO once per day, starting 1 to 2 weeks before the first dose of [[Pemetrexed (Alimta)]], 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 (Alimta)]], to be given throughout pemetrexed therapy
| |
| − | | |
| − | '''21-day cycle for up to 4 cycles'''
| |
| − | ====Subsequent treatment====
| |
| − | *[[#Pemetrexed_monotherapy_2|Pemetrexed maintenance]]
| |
| − | | |
| − | ===Regimen variant #2, 6/500 x 4 {{#subobject:ecc998|Variant=1}}===
| |
| − | {| class="wikitable sortable" style="width: 100%; text-align:center;"
| |
| − | !style="width: 20%"|Study
| |
| − | !style="width: 20%"|Years of enrollment
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !style="width: 20%"|Comparator
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
| |
| − | |-
| |
| − | |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30123-X/fulltext Soria et al. 2017 (ASCEND-4)]
| |
| − | |2013-2015
| |
| − | |style="background-color:#1a9851"|Phase 3 (C)
| |
| − | |[[#Ceritinib_monotherapy|Ceritinib]]
| |
| − | |style="background-color:#d73027"|Inferior PFS
| |
| − | |-
| |
| − | |}
| |
| − | ====Biomarker Eligibility Criteria====
| |
| − | *Biomarker: ALK Fusion Gene Rearrangement
| |
| − | *Diagnostics: IHC
| |
| − | ====Chemotherapy====
| |
| − | *[[Carboplatin (Paraplatin)]] AUC 6 IV over 15 to 60 minutes once on day 1, '''given second'''
| |
| − | *[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV over 10 minutes once on day 1, '''given first'''
| |
| − | | |
| − | ====Supportive medications====
| |
| − | *[[Dexamethasone (Decadron)]] 4 mg or [[steroid conversions|equivalent corticosteroid]] PO twice per day on the day before, the day of, and day after each dose of [[Pemetrexed (Alimta)]]
| |
| − | *[[Folic acid (Folate)]] 350 to 600 mcg PO once per day, starting 1 to 2 weeks before the first dose of [[Pemetrexed (Alimta)]], 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 (Alimta)]], to be given throughout pemetrexed therapy
| |
| − | | |
| − | '''21-day cycle for up to 4 cycles'''
| |
| − | ====Subsequent treatment====
| |
| − | *[[#Pemetrexed_monotherapy_2|Pemetrexed maintenance]]
| |
| − | | |
| − | ===References===
| |
| − | # '''ASCEND-4:''' Soria JC, Tan DS, Chiari R, Wu YL, Paz-Ares L, Wolf J, Geater SL, Orlov S, Cortinovis D, Yu CJ, Hochmair M, Cortot AB, Tsai CM, Moro-Sibilot D, Campelo RG, McCulloch T, Sen P, Dugan M, Pantano S, Branle F, Massacesi C, de Castro G Jr. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017 Mar 4;389(10072):917-929. Epub 2017 Jan 24. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30123-X/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/28126333 PubMed] NCT01828099
| |
| − | | |
| − | ==Ceritinib monotherapy {{#subobject:fe3892|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen variant #1, 450 mg/day with food {{#subobject:381ec5|Variant=1}}===
| |
| − | {| class="wikitable" style="color:white; background-color:#404040"
| |
| − | |<small>'''FDA-recommended dose'''</small>
| |
| − | |-
| |
| − | |}
| |
| − | {| class="wikitable sortable" style="width: 100%; text-align:center;"
| |
| − | !style="width: 20%"|Study
| |
| − | !style="width: 20%"|Years of enrollment
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !style="width: 20%"|Comparator
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
| |
| − | |-
| |
| − | |[https://www.jto.org/article/S1556-0864(17)30578-6/fulltext Cho et al. 2017 (ASCEND-8)]
| |
| − | |2015-2016
| |
| − | |style="background-color:#1a9851"|Randomized phase 1 (E-de-esc)
| |
| − | |[[#Ceritinib_monotherapy|Ceritinib]]; 750 mg/d
| |
| − | |style="background-color:#d3d3d3"|Not reported
| |
| − | |-
| |
| − | |}
| |
| − | ====Biomarker Eligibility Criteria====
| |
| − | *Biomarker: ALK Fusion Gene Rearrangement
| |
| − | *Diagnostics: IHC
| |
| − | | |
| − | ====Targeted therapy====
| |
| − | *[[Ceritinib (Zykadia)]] 450 mg PO once per day with food
| |
| − | | |
| − | '''Continued indefinitely'''
| |
| − | | |
| − | ===Regimen variant #2, 750 mg/day fasting {{#subobject:47c6e4|Variant=1}}=== | |
| − | {| class="wikitable sortable" style="width: 100%; text-align:center;"
| |
| − | !style="width: 20%"|Study
| |
| − | !style="width: 20%"|Years of enrollment
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !style="width: 20%"|Comparator
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079055/ Shaw et al. 2014 (ASCEND-1)]
| |
| − | |2011-2013
| |
| − | | style="background-color:#91cf61" |Phase 1, >20 pts in this dosing cohort (RT)
| |
| − | | style="background-color:#d3d3d3" |
| |
| − | | style="background-color:#d3d3d3" |
| |
| − | |-
| |
| − | |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30123-X/fulltext Soria et al. 2017 (ASCEND-4)]
| |
| − | |2013-2015
| |
| − | |style="background-color:#1a9851"|Phase 3 (E-RT-switch-ooc)
| |
| − | |1. [[#Carboplatin_.26_Pemetrexed|Carboplatin & Pemetrexed]]<br> 2. [[#Cisplatin_.26_Pemetrexed_2|Cisplatin & Pemetrexed]]
| |
| − | |style="background-color:#1a9850"|Superior PFS
| |
| − | |-
| |
| − | |[https://www.jto.org/article/S1556-0864(17)30578-6/fulltext Cho et al. 2017 (ASCEND-8)]
| |
| − | |2015-2016
| |
| − | |style="background-color:#1a9851"|Randomized phase 1 (C)
| |
| − | |[[#Ceritinib_monotherapy|Ceritinib]]; 450 mg/d
| |
| − | |style="background-color:#d3d3d3"|Not reported
| |
| − | |-
| |
| − | |}
| |
| − | ====Biomarker Eligibility Criteria====
| |
| − | *Biomarker: ALK Fusion Gene Rearrangement
| |
| − | *Diagnostics: IHC
| |
| − | ====Targeted therapy====
| |
| − | *[[Ceritinib (Zykadia)]] 750 mg PO once per day on an empty stomach
| |
| − | | |
| − | '''21-day cycles'''
| |
| − | | |
| − | ===References===
| |
| − | # '''ASCEND-1:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1311107 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079055/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24670165 PubMed] NCT01283516
| |
| − | ## '''Update:''' Kim DW, Mehra R, Tan DSW, Felip E, Chow LQM, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Sutradhar S, Li S, Szczudlo T, Yovine A, Shaw AT. Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): updated results from the multicentre, open-label, phase 1 trial. Lancet Oncol. 2016 Apr;17(4):452-463. Epub 2016 Mar 11. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00614-2/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063047/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26973324 PubMed]
| |
| − | # '''ASCEND-4:''' Soria JC, Tan DS, Chiari R, Wu YL, Paz-Ares L, Wolf J, Geater SL, Orlov S, Cortinovis D, Yu CJ, Hochmair M, Cortot AB, Tsai CM, Moro-Sibilot D, Campelo RG, McCulloch T, Sen P, Dugan M, Pantano S, Branle F, Massacesi C, de Castro G Jr. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017 Mar 4;389(10072):917-929. Epub 2017 Jan 24. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30123-X/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/28126333 PubMed] NCT01828099
| |
| − | # '''ASCEND-8:''' Cho BC, Kim DW, Bearz A, Laurie SA, McKeage M, Borra G, Park K, Kim SW, Ghosn M, Ardizzoni A, Maiello E, Greystoke A, Yu R, Osborne K, Gu W, Scott JW, Passos VQ, Lau YY, Wrona A. ASCEND-8: a randomized phase 1 study of ceritinib, 450 mg or 600 mg, taken with a low-fat meal versus 750 mg in fasted state in patients with anaplastic lymphoma kinase (ALK)-rearranged metastatic non-small cell lung cancer (NSCLC). J Thorac Oncol. 2017 Sep;12(9):1357-1367. Epub 2017 Jul 17. [https://www.jto.org/article/S1556-0864(17)30578-6/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/28729021 PubMed] NCT02299505
| |
| − | | |
| − | ==Cisplatin & Pemetrexed {{#subobject:af12b4|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | Pem-Cis: '''<u>Pem</u>'''etrexed & '''<u>Cis</u>'''platin
| |
| − | <br>Cis-Pem: '''<u>Cis</u>'''platin & '''<u>Pem</u>'''etrexed
| |
| − | | |
| − | ===Regimen variant #2, 75/500 {{#subobject:8fdaa3|Variant=1}}===
| |
| − | {| class="wikitable" style="color:white; background-color:#404040"
| |
| − | |<small>'''FDA-recommended dose'''</small>
| |
| − | |-
| |
| − | |}
| |
| − | {| class="wikitable sortable" style="width: 100%; text-align:center;"
| |
| − | !style="width: 20%"|Study
| |
| − | !style="width: 20%"|Years of enrollment
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !style="width: 20%"|Comparator
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
| |
| − | |-
| |
| − | |[https://www.nejm.org/doi/full/10.1056/NEJMoa1408440 Solomon et al. 2014 (PROFILE 1014)]
| |
| − | |2011-2013
| |
| − | |style="background-color:#1a9851"|Phase 3 (C)
| |
| − | |[[#Crizotinib_monotherapy|Crizotinib]]
| |
| − | |style="background-color:#d73027"|Inferior PFS
| |
| − | |-
| |
| − | |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30123-X/fulltext Soria et al. 2017 (ASCEND-4)]
| |
| − | |2013-2015
| |
| − | |style="background-color:#1a9851"|Phase 3 (C)
| |
| − | |[[#Ceritinib_monotherapy|Ceritinib]]
| |
| − | |style="background-color:#d73027"|Inferior PFS
| |
| − | |-
| |
| − | |}
| |
| − | ====Biomarker eligibility criteria====
| |
| − | Biomarker: ALK Fusion Gene Rearrangement
| |
| − | Diagnostics: FISH or IHC
| |
| − | ====Chemotherapy====
| |
| − | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1, '''given second'''
| |
| − | *[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV over 10 minutes once on day 1, '''given first'''
| |
| − | | |
| − | ====Supportive medications====
| |
| − | *(as described in JMDB):
| |
| − | *[[Cyanocobalamin (Vitamin B12)]] 1000 mcg IM every 9 weeks, first dose prior to [[Pemetrexed (Alimta)]]
| |
| − | *[[Folic acid (Folate)]] 1 mg PO once per day
| |
| − | *In Sequist et al. 2013: Patients "received [[Folic acid (Folate)]], vitamin B12, and dexamethasone, as per package recommendations for [[Pemetrexed (Alimta)]]."
| |
| − | | |
| − | '''21-day cycle for 4 to 6 cycles'''
| |
| − | ====Subsequent treatment====
| |
| − | *ASCEND-4: [[#Pemetrexed_monotherapy_2|Pemetrexed maintenance]]
| |
| − | | |
| − | ===References===
| |
| − | # '''PROFILE 1014:''' Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, Iyer S, Reisman A, Wilner KD, Tursi J, Blackhall F; PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014 Dec 4;371(23):2167-77. Erratum in: N Engl J Med. 2015 Oct 15;373(16):1582. [https://www.nejm.org/doi/full/10.1056/NEJMoa1408440 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/25470694 PubMed] NCT01154140
| |
| − | ## '''Subgroup analysis:''' Solomon BJ, Cappuzzo F, Felip E, Blackhall FH, Costa DB, Kim DW, Nakagawa K, Wu YL, Mekhail T, Paolini J, Tursi J, Usari T, Wilner KD, Selaru P, Mok TS. Intracranial efficacy of crizotinib versus chemotherapy in patients with advanced ALK-positive non-small-cell lung cancer: results from PROFILE 1014. J Clin Oncol. 2016 Aug 20;34(24):2858-65. Epub 2016 Mar 28. [https://doi.org/10.1200/JCO.2015.63.5888 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27022118 PubMed]
| |
| − | ## '''Pooled subgroup analysis:''' Nishio M, Kim DW, Wu YL, Nakagawa K, Solomon BJ, Shaw AT, Hashigaki S, Ohki E, Usari T, Paolini J, Polli A, Wilner KD, Mok T. Crizotinib versus chemotherapy in Asian patients with ALK-positive advanced non-small cell lung cancer. Cancer Res Treat. 2018 Jul;50(3):691-700. Epub 2017 Jul 6. [https://www.e-crt.org/journal/view.php?doi=10.4143/crt.2017.280 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056984/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28701030 PubMed]
| |
| − | ## '''Update:''' Solomon BJ, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, Tang Y, Wilner KD, Blackhall F, Mok TS. Final overall survival analysis from a study comparing first-line crizotinib versus chemotherapy in ALK-mutation-positive non-small-cell lung cancer. J Clin Oncol. 2018 Aug 1;36(22):2251-2258. Epub 2018 May 16. [https://doi.org/10.1200/JCO.2017.77.4794 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29768118 PubMed]
| |
| − | # '''ASCEND-4:''' Soria JC, Tan DS, Chiari R, Wu YL, Paz-Ares L, Wolf J, Geater SL, Orlov S, Cortinovis D, Yu CJ, Hochmair M, Cortot AB, Tsai CM, Moro-Sibilot D, Campelo RG, McCulloch T, Sen P, Dugan M, Pantano S, Branle F, Massacesi C, de Castro G Jr. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study. Lancet. 2017 Mar 4;389(10072):917-929. Epub 2017 Jan 24. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30123-X/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/28126333 PubMed] NCT01828099
| |
| − | | |
| − | ==Crizotinib monotherapy {{#subobject:be5391|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen variant #1, 250 mg/day {{#subobject:d7fdf0|Variant=1}}===
| |
| − | {| class="wikitable" style="color:white; background-color:#404040"
| |
| − | |<small>'''FDA-recommended dose'''</small>
| |
| − | |-
| |
| − | |}
| |
| − | ''Note: this is the FDA-recommended dosing for "severe" hepatic or renal impairment.''
| |
| − | ====Targeted therapy====
| |
| − | *[[Crizotinib (Xalkori)]] 250 mg PO once per day
| |
| − | | |
| − | '''Continued indefinitely'''
| |
| − | | |
| − | ===Regimen variant #2, 400 mg/day {{#subobject:c56a8e|Variant=1}}===
| |
| − | {| class="wikitable" style="color:white; background-color:#404040"
| |
| − | |<small>'''FDA-recommended dose'''</small>
| |
| − | |-
| |
| − | |}
| |
| − | ''Note: this is the FDA-recommended dosing for "moderate" hepatic impairment.''
| |
| − | ====Targeted therapy====
| |
| − | *[[Crizotinib (Xalkori)]] 200 mg PO twice per day
| |
| − | | |
| − | '''Continued indefinitely'''
| |
| − | | |
| − | ===Regimen variant #3, 500 mg/day {{#subobject:e9c195|Variant=1}}===
| |
| − | {| class="wikitable" style="color:white; background-color:#404040"
| |
| − | |<small>'''FDA-recommended dose'''</small>
| |
| − | |-
| |
| − | |}
| |
| − | {| class="wikitable sortable" style="width: 100%; text-align:center;"
| |
| − | !style="width: 20%"|Study
| |
| − | !style="width: 20%"|Years of enrollment
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !style="width: 20%"|Comparator
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014291/ Kwak et al. 2010 (PROFILE 1001 ALK)]
| |
| − | |2008-2011
| |
| − | |style="background-color:#91cf61"|Phase 1 (RT)
| |
| − | |style="background-color:#d3d3d3"|
| |
| − | |style="background-color:#919191"|ORR: 61%
| |
| − | |-
| |
| − | |rowspan=2|[https://www.nejm.org/doi/full/10.1056/NEJMoa1214886 Shaw et al. 2013 (PROFILE 1007)]
| |
| − | |rowspan=2|2010-2012
| |
| − | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-RT-switch-ooc)
| |
| − | |1. [[#Pemetrexed_monotherapy|Pemetrexed]]
| |
| − | |style="background-color:#1a9850"|Superior PFS
| |
| − | |-
| |
| − | |2. [[#Docetaxel_monotherapy|Docetaxel]]
| |
| − | |style="background-color:#1a9850"|Superior PFS
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703388/ Blackhall et al. 2017 (PROFILE 1005)]
| |
| − | |2010-2014
| |
| − | |style="background-color:#91cf61"|Phase 2 (RT)
| |
| − | |style="background-color:#d3d3d3"|
| |
| − | |style="background-color:#d3d3d3"|
| |
| − | |-
| |
| − | |[https://www.nejm.org/doi/full/10.1056/NEJMoa1408440 Solomon et al. 2014 (PROFILE 1014)]
| |
| − | |2011-2013
| |
| − | |style="background-color:#1a9851"|Phase 3 (E-RT-switch-ooc)
| |
| − | |1. [[#Carboplatin_.26_Pemetrexed|Carboplatin & Pemetrexed]]<br> 2. [[#Cisplatin_.26_Pemetrexed|Cisplatin & Pemetrexed]]
| |
| − | |style="background-color:#1a9850"|Superior PFS
| |
| − | |-
| |
| − | |[https://www.jto.org/article/S1556-0864(18)30721-4/fulltext Wu et al. 2018 (PROFILE 1029)]
| |
| − | |2012-2014
| |
| − | |style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
| |
| − | |1. [[#Carboplatin_.26_Pemetrexed|Carboplatin & Pemetrexed]]<br> 2. [[#Cisplatin_.26_Pemetrexed|Cisplatin & Pemetrexed]]
| |
| − | |style="background-color:#1a9850"|Superior PFS
| |
| − | |-
| |
| − | |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30565-2/fulltext Hida et al. 2017 (J-ALEX)]
| |
| − | |2013-2015
| |
| − | |style="background-color:#1a9851"|Phase 3 (C)
| |
| − | |[[#Alectinib_monotherapy|Alectinib]]
| |
| − | |style="background-color:#d73027"|Inferior PFS
| |
| − | |-
| |
| − | |[https://www.nejm.org/doi/full/10.1056/NEJMoa1704795 Peters et al. 2017 (ALEX)]
| |
| − | |2014-2016
| |
| − | |style="background-color:#1a9851"|Phase 3 (C)
| |
| − | |[[#Alectinib_monotherapy|Alectinib]]
| |
| − | | style="background-color:#fc8d59" |Seems to have inferior OS
| |
| − | |-
| |
| − | |[https://www.nejm.org/doi/full/10.1056/NEJMoa1810171 Camidge et al. 2018 (ALTA-1L)]
| |
| − | |2016-2017
| |
| − | |style="background-color:#1a9851"|Phase 3 (C)
| |
| − | |[[#Brigatinib_monotherapy|Brigatinib]]
| |
| − | |style="background-color:#d73027"|Inferior PFS
| |
| − | |-
| |
| − | |[https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(19)30053-0/fulltext Zhou et al. 2019 (ALESIA)]
| |
| − | |2016-2017
| |
| − | |style="background-color:#1a9851"|Phase 3 (C)
| |
| − | |[[#Alectinib_monotherapy|Alectinib]]
| |
| − | |style="background-color:#d73027"|Inferior PFS
| |
| − | |-
| |
| − | |[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8414368/ Horn et al. 2021 (eXalt3)]
| |
| − | |2016-2018
| |
| − | |style="background-color:#1a9851"|Phase 3 (C)
| |
| − | |[[#Ensartinib_monotherapy_77|Ensartinib]]
| |
| − | |style="background-color:#d73027"|Inferior PFS
| |
| − | |-
| |
| − | |[https://doi.org/10.1056/nejmoa2027187 Shaw et al. 2020 (CROWN)]
| |
| − | |2017-2019
| |
| − | |style="background-color:#1a9851"|Phase 3 (C)
| |
| − | |[[#Lorlatinib_monotherapy|Lorlatinib]]
| |
| − | |style="background-color:#d73027"|Inferior PFS
| |
| − | |-
| |
| − | |}
| |
| − | ''Note: PROFILE 1007 used 21-day cycles, and crizotinib was similarly given 250 mg PO twice per day on all days. Reported efficacy for ALEX is based on the 2020 update; the authors mention that OS results are immature.''
| |
| − | ====Targeted therapy====
| |
| − | *[[Crizotinib (Xalkori)]] 250 mg PO twice per day
| |
| − | | |
| − | '''28-day cycles'''
| |
| − | | |
| − | ===References===
| |
| − | # '''PROFILE 1001 ALK:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1006448 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014291/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20979469 PubMed] NCT00585195
| |
| − | ## '''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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70344-3/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3936578/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/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. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328296/ link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328296/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21933749 PubMed]
| |
| − | # '''PROFILE 1007:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1214886 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1214886/suppl_file/nejmoa1214886_appendix.pdf link to supplementary appendix] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/23724913 PubMed] NCT00932893
| |
| − | ## '''Pooled subgroup analysis:''' Nishio M, Kim DW, Wu YL, Nakagawa K, Solomon BJ, Shaw AT, Hashigaki S, Ohki E, Usari T, Paolini J, Polli A, Wilner KD, Mok T. Crizotinib versus chemotherapy in Asian patients with ALK-positive advanced non-small cell lung cancer. Cancer Res Treat. 2018 Jul;50(3):691-700. Epub 2017 Jul 6. [https://www.e-crt.org/journal/view.php?doi=10.4143/crt.2017.280 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056984/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28701030 PubMed]
| |
| − | # '''PROFILE 1014:''' Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, Iyer S, Reisman A, Wilner KD, Tursi J, Blackhall F; PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014 Dec 4;371(23):2167-77. Erratum in: N Engl J Med. 2015 Oct 15;373(16):1582. [https://www.nejm.org/doi/full/10.1056/NEJMoa1408440 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/25470694 PubMed] NCT01154140
| |
| − | ## '''Subgroup analysis:''' Solomon BJ, Cappuzzo F, Felip E, Blackhall FH, Costa DB, Kim DW, Nakagawa K, Wu YL, Mekhail T, Paolini J, Tursi J, Usari T, Wilner KD, Selaru P, Mok TS. Intracranial efficacy of crizotinib versus chemotherapy in patients with advanced ALK-positive non-small-cell lung cancer: results from PROFILE 1014. J Clin Oncol. 2016 Aug 20;34(24):2858-65. Epub 2016 Mar 28. [https://doi.org/10.1200/JCO.2015.63.5888 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27022118 PubMed]
| |
| − | ## '''Pooled subgroup analysis:''' Nishio M, Kim DW, Wu YL, Nakagawa K, Solomon BJ, Shaw AT, Hashigaki S, Ohki E, Usari T, Paolini J, Polli A, Wilner KD, Mok T. Crizotinib versus chemotherapy in Asian patients with ALK-positive advanced non-small cell lung cancer. Cancer Res Treat. 2018 Jul;50(3):691-700. Epub 2017 Jul 6. [https://www.e-crt.org/journal/view.php?doi=10.4143/crt.2017.280 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056984/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28701030 PubMed]
| |
| − | ## '''Update:''' Solomon BJ, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, Tang Y, Wilner KD, Blackhall F, Mok TS. Final overall survival analysis from a study comparing first-line crizotinib versus chemotherapy in ALK-mutation-positive non-small-cell lung cancer. J Clin Oncol. 2018 Aug 1;36(22):2251-2258. Epub 2018 May 16. [https://doi.org/10.1200/JCO.2017.77.4794 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29768118 PubMed]
| |
| − | # '''J-ALEX:''' Hida T, Nokihara H, Kondo M, Kim YH, Azuma K, Seto T, Takiguchi Y, Nishio M, Yoshioka H, Imamura F, Hotta K, Watanabe S, Goto K, Satouchi M, Kozuki T, Shukuya T, Nakagawa K, Mitsudomi T, Yamamoto N, Asakawa T, Asabe R, Tanaka T, Tamura T. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet. 2017 Jul 1;390(10089):29-39. Epub 2017 May 10. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30565-2/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/28501140 PubMed] JapicCTI-132316
| |
| − | ## '''Subgroup analysis:''' Nishio M, Nakagawa K, Mitsudomi T, Yamamoto N, Tanaka T, Kuriki H, Zeaiter A, Tamura T. Analysis of central nervous system efficacy in the J-ALEX study of alectinib versus crizotinib in ALK-positive non-small-cell lung cancer. Lung Cancer. 2018 Jul;121:37-40. Epub 2018 Apr 17. [https://doi.org/10.1016/j.lungcan.2018.04.015 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29858024 PubMed]
| |
| − | # '''ALEX:''' Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, Ou SI, Pérol M, Dziadziuszko R, Rosell R, Zeaiter A, Mitry E, Golding S, Balas B, Noe J, Morcos PN, Mok T; ALEX Trial Investigators. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017 Aug 31;377(9):829-838. Epub 2017 Jun 6. [https://www.nejm.org/doi/full/10.1056/NEJMoa1704795 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/28586279 PubMed] NCT02075840
| |
| − | ## '''Subgroup analysis:''' Gadgeel S, Peters S, Mok T, Shaw AT, Kim DW, Ou SI, Pérol M, Wrona A, Novello S, Rosell R, Zeaiter A, Liu T, Nüesch E, Balas B, Camidge DR. Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study. Ann Oncol. 2018 Nov 1;29(11):2214-2222. [https://doi.org/10.1093/annonc/mdy405 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290889/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30215676 PubMed]
| |
| − | ## '''Update:''' Camidge DR, Dziadziuszko R, Peters S, Mok T, Noe J, Nowicka M, Gadgeel SM, Cheema P, Pavlakis N, de Marinis F, Cho BC, Zhang L, Moro-Sibilot D, Liu T, Bordogna W, Balas B, Müller B, Shaw AT. Updated efficacy and safety data and impact of the EML4-ALK fusion variant on the efficacy of alectinib in untreated ALK-positive advanced non-small cell lung cancer in the global phase III ALEX study. J Thorac Oncol. 2019 Jul;14(7):1233-1243. Epub 2019 Mar 20. [https://www.jto.org/article/S1556-0864(19)30210-2/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/30902613 PubMed]
| |
| − | ## '''Update:''' Mok T, Camidge DR, Gadgeel SM, Rosell R, Dziadziuszko R, Kim DW, Pérol M, Ou SI, Ahn JS, Shaw AT, Bordogna W, Smoljanović V, Hilton M, Ruf T, Noé J, Peters S. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020 Aug;31(8):1056-1064. Epub 2020 May 11. [https://doi.org/10.1016/j.annonc.2020.04.478 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32418886 PubMed]
| |
| − | # '''PROFILE 1005:''' Blackhall F, Camidge DR, Shaw AT, Soria JC, Solomon BJ, Mok T, Hirsh V, Jänne PA, Shi Y, Yang PC, Pas T, Hida T, Carpeño JC, Lanzalone S, Polli A, Iyer S, Reisman A, Wilner KD, Kim DW. Final results of the large-scale multinational trial PROFILE 1005: efficacy and safety of crizotinib in previously treated patients with advanced/metastatic ALK-positive non-small-cell lung cancer. ESMO Open. 2017 Aug 17;2(3):e000219. eCollection 2017. [https://doi.org/10.1136/esmoopen-2017-000219 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703388/ link to PMC article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/29209525 PubMed] NCT00932451
| |
| − | # '''PROFILE 1029:''' Wu YL, Lu S, Lu Y, Zhou J, Shi YK, Sriuranpong V, Ho JCM, Ong CK, Tsai CM, Chung CH, Wilner KD, Tang Y, Masters ET, Selaru P, Mok TS. Results of PROFILE 1029, a phase III comparison of first-line crizotinib versus chemotherapy in East Asian patients with ALK-positive advanced non-small cell lung cancer. J Thorac Oncol. 2018 Oct;13(10):1539-1548. Epub 2018 Aug 14. [https://www.jto.org/article/S1556-0864(18)30721-4/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/29966800 PubMed] NCT01639001
| |
| − | # '''ALTA-1L:''' Camidge DR, Kim HR, Ahn MJ, Yang JC, Han JY, Lee JS, Hochmair MJ, Li JY, Chang GC, Lee KH, Gridelli C, Delmonte A, Garcia Campelo R, Kim DW, Bearz A, Griesinger F, Morabito A, Felip E, Califano R, Ghosh S, Spira A, Gettinger SN, Tiseo M, Gupta N, Haney J, Kerstein D, Popat S. Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer. N Engl J Med. 2018 Nov 22;379(21):2027-2039. Epub 2018 Sep 25. [https://www.nejm.org/doi/full/10.1056/NEJMoa1810171 link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/30280657 PubMed] NCT02737501
| |
| − | ## '''Update:''' Camidge DR, Kim HR, Ahn MJ, Yang JCH, Han JY, Hochmair MJ, Lee KH, Delmonte A, García Campelo MR, Kim DW, Griesinger F, Felip E, Califano R, Spira A, Gettinger SN, Tiseo M, Lin HM, Gupta N, Hanley MJ, Ni Q, Zhang P, Popat S. Brigatinib Versus Crizotinib in Advanced ALK Inhibitor-Naive ALK-Positive Non-Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial. J Clin Oncol. 2020 Nov 1;38(31):3592-3603. Epub 2020 Aug 11. [https://doi.org/10.1200/jco.20.00505 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605398/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32780660 PubMed]
| |
| − | ## '''Update:''' Camidge DR, Kim HR, Ahn MJ, Yang JCH, Han JY, Hochmair MJ, Lee KH, Delmonte A, Garcia Campelo MR, Kim DW, Griesinger F, Felip E, Califano R, Spira AI, Gettinger SN, Tiseo M, Lin HM, Liu Y, Vranceanu F, Niu H, Zhang P, Popat S. Brigatinib Versus Crizotinib in ALK Inhibitor-Naive Advanced ALK-Positive NSCLC: Final Results of Phase 3 ALTA-1L Trial. J Thorac Oncol. 2021 Dec;16(12):2091-2108. Epub 2021 Sep 16. [https://doi.org/10.1016/j.jtho.2021.07.035 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34537440/ PubMed]
| |
| − | # '''ALESIA:''' Zhou C, Kim SW, Reungwetwattana T, Zhou J, Zhang Y, He J, Yang JJ, Cheng Y, Lee SH, Bu L, Xu T, Yang L, Wang C, Liu T, Morcos PN, Lu Y, Zhang L. Alectinib versus crizotinib in untreated Asian patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer (ALESIA): a randomised phase 3 study. Lancet Respir Med. 2019 May;7(5):437-446. Epub 2019 Apr 10. [https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(19)30053-0/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/30981696 PubMed] NCT02838420
| |
| − | # '''CROWN:''' Shaw AT, Bauer TM, de Marinis F, Felip E, Goto Y, Liu G, Mazieres J, Kim DW, Mok T, Polli A, Thurm H, Calella AM, Peltz G, Solomon BJ; CROWN Trial Investigators. First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. N Engl J Med. 2020 Nov 19;383(21):2018-2029. [https://doi.org/10.1056/nejmoa2027187 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33207094/ PubMed] NCT03052608
| |
| − | #'''eXalt3:''' Horn L, Wang Z, Wu G, Poddubskaya E, Mok T, Reck M, Wakelee H, Chiappori AA, Lee DH, Breder V, Orlov S, Cicin I, Cheng Y, Liu Y, Fan Y, Whisenant JG, Zhou Y, Oertel V, Harrow K, Liang C, Mao L, Selvaggi G, Wu YL. Ensartinib vs Crizotinib for Patients With Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Randomized Clinical Trial. JAMA Oncol. 2021 Nov 1;7(11):1617-1625. [https://doi.org/10.1001/jamaoncol.2021.3523 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8414368/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34473194/ PubMed] NCT02767804
| |
| − | | |
| − | ==Docetaxel monotherapy {{#subobject:fd1716|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:b495b6|Variant=1}}===
| |
| | {| class="wikitable sortable" style="width: 100%; text-align:center;" | | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
| | !style="width: 20%"|Study | | !style="width: 20%"|Study |
| − | !style="width: 20%"|Years of enrollment | + | !style="width: 20%"|Dates of enrollment |
| | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
| | !style="width: 20%"|Comparator | | !style="width: 20%"|Comparator |
| | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
| | |- | | |- |
| − | |[https://www.nejm.org/doi/full/10.1056/NEJMoa1214886 Shaw et al. 2013 (PROFILE 1007)] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844511/ Forde et al. 2022 (CheckMate 816)] |
| − | |2010-2012 | + | {| class="wikitable" style="margin:auto; color:black; background-color:#d3d3d3" |
| − | |style="background-color:#1a9851"|Phase 3 (C)
| + | |[[File:HopeAI.png|link=https://hemonc.org|alt=Alt text|Title=text|frameless|150px|center]] |
| − | |[[#Crizotinib_monotherapy|Crizotinib]]
| |
| − | |style="background-color:#d73027"|Inferior PFS
| |
| − | |- | |
| − | |}
| |
| − | Biomarker Eligibility Criteria
| |
| − | Biomarker: ALK Fusion Gene Rearrangement
| |
| − | Diagnostics: FISH
| |
| − | ====Chemotherapy====
| |
| − | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
| |
| − | | |
| − | ====Supportive medications====
| |
| − | *Per JMEI: [[Dexamethasone (Decadron)]] 8 mg PO twice per day on days -1 to 2 (3 days)
| |
| − | *Per Chem et al. 2006: [[Dexamethasone (Decadron)]] by the following split schedule:
| |
| − | **8 mg PO once per day on days 1, 8, 15; 12 hours prior to [[Docetaxel (Taxotere)]]
| |
| − | **10 mg IV once per day on days 1, 8, 15; 30 minutes prior to [[Docetaxel (Taxotere)]]
| |
| − | **8 mg PO once per day on days 1, 8, 15; 12 hours after [[Docetaxel (Taxotere)]]
| |
| − | | |
| − | '''21-day cycles'''
| |
| − | ===References===
| |
| − | # '''PROFILE 1007:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1214886 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1214886/suppl_file/nejmoa1214886_appendix.pdf link to supplementary appendix] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/23724913 PubMed] NCT00932893
| |
| − | ## '''Pooled subgroup analysis:''' Nishio M, Kim DW, Wu YL, Nakagawa K, Solomon BJ, Shaw AT, Hashigaki S, Ohki E, Usari T, Paolini J, Polli A, Wilner KD, Mok T. Crizotinib versus chemotherapy in Asian patients with ALK-positive advanced non-small cell lung cancer. Cancer Res Treat. 2018 Jul;50(3):691-700. Epub 2017 Jul 6. [https://www.e-crt.org/journal/view.php?doi=10.4143/crt.2017.280 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056984/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28701030 PubMed]
| |
| − | | |
| − | ==Lorlatinib monotherapy {{#subobject:ig994c|Regimen=1}}== | |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| | |- | | |- |
| − | |[[#top|back to top]] | + | |Click to learn more! |
| − | |}
| |
| − | ===Regimen {{#subobject:hg71b2|Variant=1}}===
| |
| − | {| class="wikitable sortable" style="color:white; background-color:#404040"
| |
| − | |<small>'''FDA-recommended dose'''</small>
| |
| | |- | | |- |
| | |} | | |} |
| − | {| class="wikitable sortable" style="width: 100%; text-align:center;"
| |
| − | !style="width: 20%"|Study
| |
| − | !style="width: 20%"|Years of enrollment
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !style="width: 20%"|Comparator
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
| |
| − | |-
| |
| − | |[https://doi.org/10.1056/nejmoa2027187 Shaw et al. 2020 (CROWN)]
| |
| | |2017-2019 | | |2017-2019 |
| − | |style="background-color:#1a9851"|Phase 3 (E-RT-switch-ic) | + | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) |
| − | |[[#Crizotinib_monotherapy|Crizotinib]] | + | |1a. [[#Carboplatin_.26_Paclitaxel_.28CP.29|CP]]<br>1b. [[#Cisplatin_.26_Vinorelbine_.28CVb.29|CVb]]<br>1c. [[#Cisplatin_.26_Docetaxel_.28DC.29|DC]] |
| − | | style="background-color:#1a9850" |Superior PFS
| + | | style="background-color:#1a9850" |Superior EFS (co-primary endpoint)<br>Median EFS: 31.6 vs 20.8 mo<br>(HR 0.63, 97.38% CI 0.43-0.91)<br><br>Superior pCR rate (co-primary endpoint)<br>pCR rate: 24% vs 2.2%<br>(OR 13.94, 99% CI 3.49-55.75) |
| − | |-
| |
| − | |}
| |
| − | ====Biomarker Eligibility Criteria====
| |
| − | *Biomarker: ALK Fusion Gene Rearrangement
| |
| − | *Diagnostics: Ventana ALK (D5F3) CDx immunohistochemical assay
| |
| − | ====Targeted therapy====
| |
| − | *[[Lorlatinib (Lorbrena)]] 100 mg PO once per day
| |
| − | | |
| − | '''28-day cycles'''
| |
| − | ===References===
| |
| − | # '''CROWN:''' Shaw AT, Bauer TM, de Marinis F, Felip E, Goto Y, Liu G, Mazieres J, Kim DW, Mok T, Polli A, Thurm H, Calella AM, Peltz G, Solomon BJ; CROWN Trial Investigators. First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer. N Engl J Med. 2020 Nov 19;383(21):2018-2029. [https://doi.org/10.1056/nejmoa2027187 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/33207094/ PubMed] NCT03052608
| |
| − | | |
| − | ==Pemetrexed monotherapy {{#subobject:24ad9b|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:4e0d06|Variant=1}}===
| |
| − | {| class="wikitable sortable" style="width: 100%; text-align:center;"
| |
| − | !style="width: 20%"|Study
| |
| − | !style="width: 20%"|Years of enrollment
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !style="width: 20%"|Comparator
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
| |
| − | |-
| |
| − | |[https://www.nejm.org/doi/full/10.1056/NEJMoa1214886 Shaw et al. 2013 (PROFILE 1007)]
| |
| − | |2010-2012 | |
| − | |style="background-color:#1a9851"|Phase 3 (C)
| |
| − | |[[#Crizotinib_monotherapy|Crizotinib]]
| |
| − | |style="background-color:#d73027"|Inferior PFS
| |
| − | |-
| |
| − | |}
| |
| − | ====Biomarker Eligibility Criteria====
| |
| − | *Biomarker: ALK Fusion Gene Rearrangement
| |
| − | *Diagnostics: FISH
| |
| − | | |
| − | ====Chemotherapy====
| |
| − | *[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV over 10 minutes once on day 1
| |
| − | | |
| − | ====Supportive medications====
| |
| − | *(per Ardizzoni et al. 2012):
| |
| − | *[[Dexamethasone (Decadron)]] 4 mg or [[steroid conversions|equivalent corticosteroid]] PO twice per day on the day before, the day of, and day after each dose of [[Pemetrexed (Alimta)]]
| |
| − | *[[Folic acid (Folate)]] 350 to 600 mcg PO once per day, starting 1 to 2 weeks before the first dose of [[Pemetrexed (Alimta)]], to be taken throughout pemetrexed therapy
| |
| − | **JMEI used [[Folic acid (Folate)]] 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 (Alimta)]], to be given throughout pemetrexed therapy
| |
| − | | |
| − | '''21-day cycles'''
| |
| − | | |
| − | ===References===
| |
| − | # '''PROFILE 1007:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1214886 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1214886/suppl_file/nejmoa1214886_appendix.pdf link to supplementary appendix] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/23724913 PubMed] NCT00932893 | |
| − | ## '''Pooled subgroup analysis:''' Nishio M, Kim DW, Wu YL, Nakagawa K, Solomon BJ, Shaw AT, Hashigaki S, Ohki E, Usari T, Paolini J, Polli A, Wilner KD, Mok T. Crizotinib versus chemotherapy in Asian patients with ALK-positive advanced non-small cell lung cancer. Cancer Res Treat. 2018 Jul;50(3):691-700. Epub 2017 Jul 6. [https://www.e-crt.org/journal/view.php?doi=10.4143/crt.2017.280 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056984/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28701030 PubMed]
| |
| − | | |
| − | =Advanced or metastatic disease, ALK inhibitor-exposed=
| |
| − | | |
| − | ==Alectinib monotherapy {{#subobject:fd419f|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]] | |
| − | |}
| |
| − | ===Regimen {{#subobject:c16da9|Variant=1}}===
| |
| − | {| class="wikitable" style="color:white; background-color:#404040"
| |
| − | |<small>'''FDA-recommended dose'''</small>
| |
| − | |-
| |
| − | |}
| |
| − | {| class="wikitable sortable" style="width: 100%; text-align:center;"
| |
| − | !style="width: 20%"|Study
| |
| − | !style="width: 20%"|Years of enrollment
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !style="width: 20%"|Comparator
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
| |
| − | |-
| |
| − | ||[https://doi.org/10.1200/JCO.2015.63.9443 Ou et al. 2015 (NP28673)]
| |
| − | |2013-2014 | |
| − | |style="background-color:#91cf61"|Phase 2 (RT)
| |
| − | |
| |
| − | | style="background-color:#8c96c6" |ORR: 50% (95% CI, 41-59)
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752892/ Shaw et al. 2015 (NP28761)]
| |
| − | |2013-2014
| |
| − | |style="background-color:#91cf61"|Phase 2 (RT)
| |
| − | |
| |
| − | | style="background-color:#8c96c6" |ORR: 48% (95% CI, 36–60)
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005013/ Novello et al. 2018 (ALUR)]
| |
| − | |NR
| |
| − | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | |
| − | |1. [[#Docetaxel_monotherapy_2|Docetaxel]]<br> 2. [[#Pemetrexed_monotherapy_2|Pemetrexed]]
| |
| − | | style="background-color:#1a9850" |Superior PFS
| |
| − | |-
| |
| − | |}
| |
| − | ====Biomarker Eligibility Criteria====
| |
| − | *Biomarker: ALK Fusion Gene Rearrangement
| |
| − | *Diagnostics: FISH
| |
| − | | |
| − | ====Targeted therapy====
| |
| − | *[[Alectinib (Alecensa)]] 600 mg PO twice per day, to be taken within 30 minutes of eating
| |
| − | | |
| − | '''Continued indefinitely'''
| |
| − | | |
| − | ===References===
| |
| − | # '''NP28673:''' 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. Epub 2015 Nov 23. [https://doi.org/10.1200/JCO.2015.63.9443 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/26598747 PubMed] NCT01801111
| |
| − | ##'''Pooled update:''' Ou SI, Gadgeel SM, Barlesi F, Yang JC, De Petris L, Kim DW, Govindan R, Dingemans AM, Crino L, Léna H, Popat S, Ahn JS, Dansin E, Mitry E, Müller B, Bordogna W, Balas B, Morcos PN, Shaw AT. Pooled overall survival and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small-cell lung cancer. Lung Cancer. 2020 Jan;139:22-27. Epub 2019 Oct 14. [https://doi.org/10.1016/j.lungcan.2019.10.015 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31706099/ PubMed]
| |
| − | <!-- # '''Abstract:''' 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] --> | |
| − | # '''NP28761:''' Shaw AT, Gandhi L, Gadgeel S, Riely GJ, Cetnar J, West H, Camidge DR, Socinski MA, Chiappori A, Mekhail T, Chao BH, Borghaei H, Gold KA, Zeaiter A, Bordogna W, Balas B, Puig O, Henschel V, Ou SI; study investigators. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol. 2016 Feb;17(2):234-242. Epub 2015 Dec 19. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00488-X/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752892/ link to PMC article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/26708155 PubMed] NCT01871805
| |
| − | ##'''Pooled update:''' Ou SI, Gadgeel SM, Barlesi F, Yang JC, De Petris L, Kim DW, Govindan R, Dingemans AM, Crino L, Léna H, Popat S, Ahn JS, Dansin E, Mitry E, Müller B, Bordogna W, Balas B, Morcos PN, Shaw AT. Pooled overall survival and safety data from the pivotal phase II studies (NP28673 and NP28761) of alectinib in ALK-positive non-small-cell lung cancer. Lung Cancer. 2020 Jan;139:22-27. Epub 2019 Oct 14. [https://doi.org/10.1016/j.lungcan.2019.10.015 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31706099/ PubMed]
| |
| − | # '''ALUR:''' Novello S, Mazières J, Oh IJ, de Castro J, Migliorino MR, Helland Å, Dziadziuszko R, Griesinger F, Kotb A, Zeaiter A, Cardona A, Balas B, Johannsdottir HK, Das-Gupta A, Wolf J. Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study. Ann Oncol. 2018 Jun 1;29(6):1409-1416. [https://doi.org/10.1093/annonc/mdy121 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005013/ link to PMC article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/29668860 PubMed] NCT02604342
| |
| − | # '''ALTA-3:''' NCT03596866
| |
| − | | |
| − | ==Brigatinib monotherapy {{#subobject:dc24d8|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:a9648f|Variant=1}}===
| |
| − | {| class="wikitable" style="color:white; background-color:#404040"
| |
| − | |<small>'''FDA-recommended dose'''</small>
| |
| − | |-
| |
| − | |}
| |
| − | {| class="wikitable sortable" style="width: 100%; text-align:center;"
| |
| − | !style="width: 20%"|Study
| |
| − | !style="width: 20%"|Years of enrollment
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !style="width: 20%"|Comparator
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
| |
| − | |-
| |
| − | |[https://doi.org/10.1200/JCO.2016.71.5904 Kim et al. 2017 (ALTA)]
| |
| − | |2014-2015
| |
| − | |style="background-color:#1a9851"|Randomized Phase 2 (E-RT-esc)
| |
| − | |[[#Brigatinib_monotherapy_2|Brigatinib]]; 90 mg/day
| |
| − | |style="background-color:#ffffbf"|Seems not superior
| |
| − | |-
| |
| − | |}
| |
| − | ''Note: a chi-square analysis of the ORR (not reported in the manuscript; our analysis) gives a non-significant ORR increase, 54% versus 45% (p=0.18).''
| |
| − | ====Biomarker Eligibility Criteria====
| |
| − | *Biomarker: ALK Fusion Gene Rearrangement
| |
| − | | |
| − | ====Targeted therapy====
| |
| − | *[[Brigatinib (Alunbrig)]] as follows:
| |
| − | **Lead-in: 90 mg PO once per day for 7 days
| |
| − | **Subsequently: 180 mg PO once per day
| |
| − | | |
| − | '''Continued indefinitely'''
| |
| − | | |
| − | ===References===
| |
| − | <!-- # '''Abstract:''' Dong-Wan Kim, Marcello Tiseo, Myung-Ju Ahn, Karen L. Reckamp, Karin Holmskov Hansen, Sang-We Kim, Rudolf M. Huber, Howard Jack West, Harry J.M. Groen, Maximilian J. Hochmair, Natasha B. Leighl, Scott N. Gettinger, Corey J. Langer, Luis G. Paz-Ares, Egbert F. Smit, Edward S. Kim, William G Reichmann, David Kerstein, Frank G. Haluska, D. Ross Camidge. Brigatinib (BRG) in patients (pts) with crizotinib (CRZ)-refractory ALK+ non-small cell lung cancer (NSCLC): First report of efficacy and safety from a pivotal randomized phase (ph) 2 trial (ALTA). 2016 ASCO Annual Meeting abstract 9007. [http://meetinglibrary.asco.org/content/165056-176 link to abstract] [https://clinicaltrials.gov/ct2/show/NCT02094573 A Phase 2, Multicenter, Randomized Study of AP26113 (ALTA) (NCT02094573) at ClinicalTrials.gov] -->
| |
| − | # '''ALTA:''' Kim DW, Tiseo M, Ahn MJ, Reckamp KL, Hansen KH, Kim SW, Huber RM, West HL, Groen HJM, Hochmair MJ, Leighl NB, Gettinger SN, Langer CJ, Paz-Ares Rodríguez LG, Smit EF, Kim ES, Reichmann W, Haluska FG, Kerstein D, Camidge DR. Brigatinib in patients with crizotinib-refractory anaplastic lymphoma kinase-positive non-small-cell lung cancer: a randomized, multicenter phase II trial. J Clin Oncol. 2017 Aug 1;35(22):2490-2498. Epub 2017 May 5. [https://doi.org/10.1200/JCO.2016.71.5904 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/28475456 PubMed] NCT02094573
| |
| − | ## '''Subgroup analysis:''' Camidge DR, Kim DW, Tiseo M, Langer CJ, Ahn MJ, Shaw AT, Huber RM, Hochmair MJ, Lee DH, Bazhenova LA, Gold KA, Ou SI, West HL, Reichmann W, Haney J, Clackson T, Kerstein D, Gettinger SN. Exploratory analysis of brigatinib activity in patients with anaplastic lymphoma kinase-positive non-small-cell lung cancer and brain metastases in two clinical trials. J Clin Oncol. 2018 Sep 10;36(26):2693-2701. Epub 2018 May 16. [https://doi.org/10.1200/JCO.2017.77.5841 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29768119 PubMed]
| |
| − | # '''ALTA-3:''' NCT03596866
| |
| − | | |
| − | ==Ceritinib monotherapy {{#subobject:d35518|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen variant #1, 450 mg/day with food {{#subobject:2ff82e|Variant=1}}===
| |
| − | {| class="wikitable" style="color:white; background-color:#404040"
| |
| − | |<small>'''FDA-recommended dose'''</small>
| |
| | |- | | |- |
| | |} | | |} |
| − | {| class="wikitable sortable" style="width: 100%; text-align:center;"
| + | ''Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details.'' |
| − | !style="width: 20%"|Study
| + | <div class="toccolours" style="background-color:#fdcdac"> |
| − | !style="width: 20%"|Years of enrollment
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !style="width: 20%"|Comparator
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
| |
| − | |-
| |
| − | |[https://www.jto.org/article/S1556-0864(17)30578-6/fulltext Cho et al. 2017 (ASCEND-8)]
| |
| − | |2015-2016
| |
| − | |style="background-color:#1a9851"|Randomized phase 1 (de-esc)
| |
| − | |[[#Ceritinib_monotherapy_2|Ceritinib]]; 750 mg/d
| |
| − | |style="background-color:#d3d3d3"|Not reported
| |
| − | |-
| |
| − | |}
| |
| − | | |
| − | ====Biomarker Eligibility Criteria====
| |
| − | *Biomarker: ALK Fusion Gene Rearrangement
| |
| − | *Diagnostics: FISH or IHC
| |
| − | | |
| − | ====Targeted therapy====
| |
| − | *[[Ceritinib (Zykadia)]] 450 mg PO once per day with food
| |
| − | | |
| − | '''Continued indefinitely''' | |
| − | | |
| − | ===Regimen variant #2, 750 mg/day fasting {{#subobject:a93389|Variant=1}}===
| |
| − | {| class="wikitable sortable" style="width: 100%; text-align:center;"
| |
| − | !style="width: 20%"|Study
| |
| − | !style="width: 20%"|Years of enrollment
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !style="width: 20%"|Comparator
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079055/ Shaw et al. 2014 (ASCEND-1)]
| |
| − | |2011-2013
| |
| − | | style="background-color:#91cf61" |Phase 1, >20 pts in this dosing cohort (RT)
| |
| − | | style="background-color:#d3d3d3" |
| |
| − | | style="background-color:#d3d3d3" |
| |
| − | |-
| |
| − | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30339-X/fulltext Shaw et al. 2017 (ASCEND-5)]
| |
| − | |2013-2015
| |
| − | |style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
| |
| − | |1. [[#Docetaxel_monotherapy_2|Docetaxel]]<br> 2. [[#Pemetrexed_monotherapy_2|Pemetrexed]]
| |
| − | |style="background-color:#1a9850"|Superior PFS
| |
| − | |-
| |
| − | |[https://www.jto.org/article/S1556-0864(17)30578-6/fulltext Cho et al. 2017 (ASCEND-8)]
| |
| − | |2015-2016
| |
| − | |style="background-color:#1a9851"|Randomized phase 1 (C)
| |
| − | |[[#Ceritinib_monotherapy_2|Ceritinib]]; 450 mg/d
| |
| − | |style="background-color:#d3d3d3"|Not reported
| |
| − | |-
| |
| − | |}
| |
| − | ====Biomarker Eligibility Criteria====
| |
| − | *Biomarker: ALK Fusion Gene Rearrangement
| |
| − | *Diagnostics: FISH or IHC
| |
| − | | |
| − | ====Targeted therapy====
| |
| − | *[[Ceritinib (Zykadia)]] 750 mg PO once per day on an empty stomach
| |
| − | | |
| − | '''21-day cycles'''
| |
| − | | |
| − | ===References===
| |
| − | # '''ASCEND-1:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1311107 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079055/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24670165 PubMed] NCT01283516
| |
| − | ## '''Update:''' Kim DW, Mehra R, Tan DSW, Felip E, Chow LQM, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Sutradhar S, Li S, Szczudlo T, Yovine A, Shaw AT. Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): updated results from the multicentre, open-label, phase 1 trial. Lancet Oncol. 2016 Apr;17(4):452-463. Epub 2016 Mar 11. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00614-2/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063047/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26973324 PubMed]
| |
| − | # '''ASCEND-5:''' Shaw AT, Kim TM, Crinò L, Gridelli C, Kiura K, Liu G, Novello S, Bearz A, Gautschi O, Mok T, Nishio M, Scagliotti G, Spigel DR, Deudon S, Zheng C, Pantano S, Urban P, Massacesi C, Viraswami-Appanna K, Felip E. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2017 Jul;18(7):874-886. Epub 2017 Jun 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30339-X/fulltext link to original article]'''contains protocol'''[https://pubmed.ncbi.nlm.nih.gov/28602779 PubMed] NCT01828112
| |
| − | # '''ASCEND-8:''' Cho BC, Kim DW, Bearz A, Laurie SA, McKeage M, Borra G, Park K, Kim SW, Ghosn M, Ardizzoni A, Maiello E, Greystoke A, Yu R, Osborne K, Gu W, Scott JW, Passos VQ, Lau YY, Wrona A. ASCEND-8: a randomized phase 1 study of ceritinib, 450 mg or 600 mg, taken with a low-fat meal versus 750 mg in fasted state in patients with anaplastic lymphoma kinase (ALK)-rearranged metastatic non-small cell lung cancer (NSCLC). J Thorac Oncol. 2017 Sep;12(9):1357-1367. Epub 2017 Jul 17. [https://www.jto.org/article/S1556-0864(17)30578-6/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/28729021 PubMed] NCT02299505
| |
| − | | |
| − | ==Docetaxel monotherapy {{#subobject:fd1716|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:b495b6|Variant=1}}===
| |
| − | {| class="wikitable sortable" style="width: 100%; text-align:center;"
| |
| − | !style="width: 20%"|Study
| |
| − | !style="width: 20%"|Years of enrollment
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !style="width: 20%"|Comparator
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
| |
| − | |-
| |
| − | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30339-X/fulltext Shaw et al. 2017 (ASCEND-5)]
| |
| − | |2013-2015
| |
| − | |style="background-color:#1a9851"|Phase 3 (C)
| |
| − | |[[#Ceritinib_monotherapy_2|Ceritinib]]
| |
| − | |style="background-color:#d73027"|Inferior PFS
| |
| − | |-
| |
| − | |}
| |
| − | ====Biomarker Eligibility Criteria====
| |
| − | *Biomarker: ALK Fusion Gene Rearrangement
| |
| − | *Diagnostics: FISH or IHC
| |
| − | | |
| − | ====Chemotherapy====
| |
| − | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
| |
| − | | |
| − | ====Supportive medications====
| |
| − | *Per JMEI: [[Dexamethasone (Decadron)]] 8 mg PO twice per day on days -1 to 2 (3 days)
| |
| − | *Per Chem et al. 2006: [[Dexamethasone (Decadron)]] by the following split schedule:
| |
| − | **8 mg PO once per day on days 1, 8, 15; 12 hours prior to [[Docetaxel (Taxotere)]]
| |
| − | **10 mg IV once per day on days 1, 8, 15; 30 minutes prior to [[Docetaxel (Taxotere)]]
| |
| − | **8 mg PO once per day on days 1, 8, 15; 12 hours after [[Docetaxel (Taxotere)]]
| |
| − | | |
| − | '''21-day cycles'''
| |
| − | | |
| − | ===References===
| |
| − | # '''ASCEND-5:''' Shaw AT, Kim TM, Crinò L, Gridelli C, Kiura K, Liu G, Novello S, Bearz A, Gautschi O, Mok T, Nishio M, Scagliotti G, Spigel DR, Deudon S, Zheng C, Pantano S, Urban P, Massacesi C, Viraswami-Appanna K, Felip E. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2017 Jul;18(7):874-886. Epub 2017 Jun 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30339-X/fulltext link to original article]'''contains protocol'''[https://pubmed.ncbi.nlm.nih.gov/28602779 PubMed] NCT01828112
| |
| − | # '''ALUR:''' Novello S, Mazières J, Oh IJ, de Castro J, Migliorino MR, Helland Å, Dziadziuszko R, Griesinger F, Kotb A, Zeaiter A, Cardona A, Balas B, Johannsdottir HK, Das-Gupta A, Wolf J. Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study. Ann Oncol. 2018 Jun 1;29(6):1409-1416. [https://doi.org/10.1093/annonc/mdy121 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005013/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29668860 PubMed] NCT02604342
| |
| − | | |
| − | ==Lorlatinib monotherapy {{#subobject:ea894c|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:9134b2|Variant=1}}===
| |
| − | {| class="wikitable" style="color:white; background-color:#404040"
| |
| − | |<small>'''FDA-recommended dose'''</small>
| |
| − | |-
| |
| − | |}
| |
| − | {| class="wikitable" style="width: 60%; text-align:center;"
| |
| − | !style="width: 33%"|Study
| |
| − | !style="width: 33%"|Years of enrollment
| |
| − | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5777233/ Shaw et al. 2017 (B7461001)]
| |
| − | |2014-2016
| |
| − | | style="background-color:#91cf61" |Phase 1/2 (RT)
| |
| − | |-
| |
| − | |}
| |
| − | ====Biomarker Eligibility Criteria====
| |
| − | *Biomarker: ALK Fusion Gene Rearrangement
| |
| − | *Diagnostics: FISH or IHC
| |
| − | ====Targeted therapy====
| |
| − | *[[Lorlatinib (Lorbrena)]] 100 mg PO once per day
| |
| − | | |
| − | '''Continued indefinitely'''
| |
| − | | |
| − | ===References===
| |
| − | # '''B7461001:''' Shaw AT, Felip E, Bauer TM, Besse B, Navarro A, Postel-Vinay S, Gainor JF, Johnson M, Dietrich J, James LP, Clancy JS, Chen J, Martini JF, Abbattista A, Solomon BJ. Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017 Dec;18(12):1590-1599. Epub 2017 Oct 23. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30680-0/fulltext link to original article] '''contains protocol''' [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5777233/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29074098 PubMed] NCT01970865
| |
| − | ##'''Update:''' Solomon BJ, Besse B, Bauer TM, Felip E, Soo RA, Camidge DR, Chiari R, Bearz A, Lin CC, Gadgeel SM, Riely GJ, Tan EH, Seto T, James LP, Clancy JS, Abbattista A, Martini JF, Chen J, Peltz G, Thurm H, Ou SI, Shaw AT. Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. Lancet Oncol. 2018 Dec;19(12):1654-1667. Epub 2018 Nov 6. Erratum in: Lancet Oncol. 2019 Jan;20(1):e10. [https://doi.org/10.1016/s1470-2045(18)30649-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30413378/ PubMed]
| |
| − | | |
| − | ==Pemetrexed monotherapy {{#subobject:24ad9b|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:4e0d06|Variant=1}}===
| |
| − | {| class="wikitable sortable" style="width: 100%; text-align:center;"
| |
| − | !style="width: 20%"|Study
| |
| − | !style="width: 20%"|Years of enrollment
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !style="width: 20%"|Comparator
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
| |
| − | |-
| |
| − | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30339-X/fulltext Shaw et al. 2017 (ASCEND-5)]
| |
| − | |2013-2015
| |
| − | |style="background-color:#1a9851"|Phase 3 (C)
| |
| − | |[[#Ceritinib_monotherapy_2|Ceritinib]]
| |
| − | |style="background-color:#d73027"|Inferior PFS
| |
| − | |-
| |
| − | |}
| |
| − | ====Biomarker Eligibility Criteria====
| |
| − | *Biomarker: ALK Fusion Gene Rearrangement
| |
| − | *Diagnostics: FISH or IHC
| |
| − | ====Chemotherapy====
| |
| − | *[[Pemetrexed (Alimta)]] 500 mg/m<sup>2</sup> IV over 10 minutes once on day 1
| |
| − | | |
| − | ====Supportive medications====
| |
| − | *(per Ardizzoni et al. 2012):
| |
| − | *[[Dexamethasone (Decadron)]] 4 mg or [[steroid conversions|equivalent corticosteroid]] PO twice per day on the day before, the day of, and day after each dose of [[Pemetrexed (Alimta)]]
| |
| − | *[[Folic acid (Folate)]] 350 to 600 mcg PO once per day, starting 1 to 2 weeks before the first dose of [[Pemetrexed (Alimta)]], to be taken throughout pemetrexed therapy
| |
| − | **JMEI used [[Folic acid (Folate)]] 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 (Alimta)]], to be given throughout pemetrexed therapy
| |
| − | | |
| − | '''21-day cycles'''
| |
| − | | |
| − | ===References===
| |
| − | # '''ASCEND-5:''' Shaw AT, Kim TM, Crinò L, Gridelli C, Kiura K, Liu G, Novello S, Bearz A, Gautschi O, Mok T, Nishio M, Scagliotti G, Spigel DR, Deudon S, Zheng C, Pantano S, Urban P, Massacesi C, Viraswami-Appanna K, Felip E. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2017 Jul;18(7):874-886. Epub 2017 Jun 9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30339-X/fulltext link to original article]'''contains protocol'''[https://pubmed.ncbi.nlm.nih.gov/28602779 PubMed] NCT01828112
| |
| − | # '''ALUR:''' Novello S, Mazières J, Oh IJ, de Castro J, Migliorino MR, Helland Å, Dziadziuszko R, Griesinger F, Kotb A, Zeaiter A, Cardona A, Balas B, Johannsdottir HK, Das-Gupta A, Wolf J. Alectinib versus chemotherapy in crizotinib-pretreated anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer: results from the phase III ALUR study. Ann Oncol. 2018 Jun 1;29(6):1409-1416. [https://doi.org/10.1093/annonc/mdy121 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005013/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29668860 PubMed] NCT02604342
| |
| − | | |
| − | =CNS metastases, all lines of therapy=
| |
| − | ==Alectinib monotherapy {{#subobject:b1194c|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen variant #1, 300 mg twice per day {{#subobject:9cef11|Variant=1}}===
| |
| − | {| class="wikitable sortable" style="width: 100%; text-align:center;"
| |
| − | !style="width: 20%"|Study
| |
| − | !style="width: 20%"|Years of enrollment
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !style="width: 20%"|Comparator
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
| |
| − | |-
| |
| − | |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30565-2/fulltext Hida et al. 2017 (J-ALEX)]
| |
| − | |2013-2015
| |
| − | | style="background-color:#1a9851" |Phase 3 (E-switch-ic)
| |
| − | |[[#Crizotinib_monotherapy_88|Crizotinib]]
| |
| − | | style="background-color:#1a9850" |Superior TTP<sup>1</sup>
| |
| − | |-
| |
| − | |}
| |
| − | ''<sup>1</sup>Reported CNS efficacy is based on the 2018 update.''<br>
| |
| − | ''Note: This is the PMDA-approved dose in Japan.''
| |
| − | | |
| | ====Biomarker eligibility criteria==== | | ====Biomarker eligibility criteria==== |
| − | | + | *CheckMate 816: No sensitizing EGFR or ALK mutations |
| − | *Gene [[Biomarkers#Genes#ALK|ALK]] positive | + | </div></div> |
| − | | |
| − | ====Targeted therapy====
| |
| − | | |
| − | *[[Alectinib (Alecensa)]] 300 mg PO twice per day
| |
| − | | |
| − | '''Continued indefinitely'''
| |
| − | | |
| − | ===Regimen variant #2, 600 mg twice per day {{#subobject:92a408|Variant=1}}===
| |
| − | {| class="wikitable sortable" style="width: 100%; text-align:center;"
| |
| − | !style="width: 20%"|Study
| |
| − | !style="width: 20%"|Years of enrollment
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | !style="width: 20%"|Comparator
| |
| − | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
| |
| − | |-
| |
| − | |[https://www.nejm.org/doi/full/10.1056/NEJMoa1704795 Peters et al. 2017 (ALEX)]
| |
| − | |2014-2016
| |
| − | | style="background-color:#1a9851" |Phase 3 (E-switch-ic)
| |
| − | |[[#Crizotinib_monotherapy_88|Crizotinib]]
| |
| − | | style="background-color:#1a9850" |Superior TTP<sup>1</sup>
| |
| − | |-
| |
| − | |}
| |
| − | ''<sup>1</sup>Reported CNS efficacy is based on the 2018 update.''
| |
| − | | |
| − | ====Biomarker eligibility criteria====
| |
| − | | |
| − | *[[Biomarkers#Genes#ALK|ALK]] positive
| |
| − | | |
| − | ====Targeted therapy====
| |
| − | | |
| − | *[[Alectinib (Alecensa)]] 600 mg PO twice per day
| |
| − | | |
| − | '''Continued indefinitely'''
| |
| − | | |
| − | ===References===
| |
| − | | |
| − | #'''J-ALEX:''' Hida T, Nokihara H, Kondo M, Kim YH, Azuma K, Seto T, Takiguchi Y, Nishio M, Yoshioka H, Imamura F, Hotta K, Watanabe S, Goto K, Satouchi M, Kozuki T, Shukuya T, Nakagawa K, Mitsudomi T, Yamamoto N, Asakawa T, Asabe R, Tanaka T, Tamura T. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet. 2017 Jul 1;390(10089):29-39. Epub 2017 May 10. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30565-2/fulltext link to original article]'''contains protocol'''[https://pubmed.ncbi.nlm.nih.gov/28501140 PubMed] JapicCTI-132316
| |
| − | ##'''Subgroup analysis:''' Nishio M, Nakagawa K, Mitsudomi T, Yamamoto N, Tanaka T, Kuriki H, Zeaiter A, Tamura T. Analysis of central nervous system efficacy in the J-ALEX study of alectinib versus crizotinib in ALK-positive non-small-cell lung cancer. Lung Cancer. 2018 Jul;121:37-40. Epub 2018 Apr 17. [https://doi.org/10.1016/j.lungcan.2018.04.015 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29858024 PubMed]
| |
| − | #'''ALEX:''' Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, Ou SI, Pérol M, Dziadziuszko R, Rosell R, Zeaiter A, Mitry E, Golding S, Balas B, Noe J, Morcos PN, Mok T; ALEX Trial Investigators. Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 2017 Aug 31;377(9):829-838. Epub 2017 Jun 6. [https://www.nejm.org/doi/full/10.1056/NEJMoa1704795 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/28586279 PubMed] NCT02075840
| |
| − | ##'''Subgroup analysis:''' Gadgeel S, Peters S, Mok T, Shaw AT, Kim DW, Ou SI, Pérol M, Wrona A, Novello S, Rosell R, Zeaiter A, Liu T, Nüesch E, Balas B, Camidge DR. Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study. Ann Oncol. 2018 Nov 1;29(11):2214-2222. [https://doi.org/10.1093/annonc/mdy405 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290889/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30215676 PubMed]
| |
| − | | |
| − | ==Ceritinib monotherapy {{#subobject:d35518|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:a93389|Variant=1}}===
| |
| − | {| class="wikitable sortable" style="width: 60%; text-align:center;"
| |
| − | !style="width: 33%"|Study
| |
| − | !style="width: 33%"|Years of enrollment
| |
| − | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079055/ Shaw et al. 2014 (ASCEND-1)]
| |
| − | |2011-2013
| |
| − | | style="background-color:#91cf61" |Phase 1, >20 pts in this dosing cohort
| |
| − | |-
| |
| − | |}
| |
| − | ''Note: CNS efficacy is based on the 2016 update.''
| |
| − | ====Targeted therapy====
| |
| − | | |
| − | *[[Ceritinib (Zykadia)]] 750 mg PO once per day on an empty stomach
| |
| − | | |
| − | '''21-day cycles'''
| |
| − | | |
| − | ===References===
| |
| − | | |
| − | #'''ASCEND-1:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1311107 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079055/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24670165 PubMed] NCT01283516
| |
| − | ##'''Update:''' Kim DW, Mehra R, Tan DSW, Felip E, Chow LQM, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Sutradhar S, Li S, Szczudlo T, Yovine A, Shaw AT. Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): updated results from the multicentre, open-label, phase 1 trial. Lancet Oncol. 2016 Apr;17(4):452-463. Epub 2016 Mar 11. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00614-2/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5063047/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26973324 PubMed]
| |
| − | | |
| − | [[Category:Non-small cell lung cancer regimens]]
| |
| − | [[Category:Biomarker-specific pages]]
| |
| − | [[Category:Non-small cell lung cancers]]
| |
