Difference between revisions of "Non-small cell lung cancer, ALK-positive"
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| − | |[ | + | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70142-6/fulltext Seto et al. 2013 (AF-001JP)] |
|style="background-color:#91cf61"|Phase I/II | |style="background-color:#91cf61"|Phase I/II | ||
|style="background-color:#d3d3d3"| | |style="background-color:#d3d3d3"| | ||
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| − | |[ | + | |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30565-2/fulltext Hida et al. 2017 (J-ALEX)] |
|style="background-color:#1a9851"|Phase III (E) | |style="background-color:#1a9851"|Phase III (E) | ||
|[[#Crizotinib_monotherapy|Crizotinib]] | |[[#Crizotinib_monotherapy|Crizotinib]] | ||
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===References=== | ===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. [ | + | # '''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://www.ncbi.nlm.nih.gov/pubmed/23639470 PubMed] |
## '''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. [http://ascopubs.org/doi/full/10.1200/JCO.2016.70.5749 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455704/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28296581 PubMed] | ## '''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. [http://ascopubs.org/doi/full/10.1200/JCO.2016.70.5749 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455704/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/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. [ | + | # '''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://www.ncbi.nlm.nih.gov/pubmed/28501140 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1704795 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28586279 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1704795 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28586279 PubMed] | ||
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![[Levels_of_Evidence#Efficacy|Efficacy]] | ![[Levels_of_Evidence#Efficacy|Efficacy]] | ||
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| − | |[ | + | |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30123-X/fulltext Soria et al. 2017 (ASCEND-4)] |
|style="background-color:#1a9851"|Phase III | |style="background-color:#1a9851"|Phase III | ||
|[[Non-small_cell_lung_cancer#Carboplatin_.26_Pemetrexed|Carboplatin & Pemetrexed]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Pemetrexed_2|Cisplatin & Pemetrexed]] | |[[Non-small_cell_lung_cancer#Carboplatin_.26_Pemetrexed|Carboplatin & Pemetrexed]]<br> [[Non-small_cell_lung_cancer#Cisplatin_.26_Pemetrexed_2|Cisplatin & Pemetrexed]] | ||
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===References=== | ===References=== | ||
# '''Phase I:''' Shaw AT, Kim DW, Mehra R, Tan DS, Felip E, Chow LQ, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Lau YY, Goldwasser M, Boral AL, Engelman JA. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Mar 27;370(13):1189-97. [http://www.nejm.org/doi/full/10.1056/NEJMoa1311107 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079055/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24670165 PubMed] | # '''Phase I:''' Shaw AT, Kim DW, Mehra R, Tan DS, Felip E, Chow LQ, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Lau YY, Goldwasser M, Boral AL, Engelman JA. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Mar 27;370(13):1189-97. [http://www.nejm.org/doi/full/10.1056/NEJMoa1311107 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079055/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24670165 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. [ | + | # '''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://www.ncbi.nlm.nih.gov/pubmed/28126333 PubMed] |
# '''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://www.ncbi.nlm.nih.gov/pubmed/28729021 PubMed] | # '''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://www.ncbi.nlm.nih.gov/pubmed/28729021 PubMed] | ||
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|style="background-color:#1a9850"|Superior PFS | |style="background-color:#1a9850"|Superior PFS | ||
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| − | |[ | + | |[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30565-2/fulltext Hida et al. 2017 (J-ALEX)] |
|style="background-color:#1a9851"|Phase III | |style="background-color:#1a9851"|Phase III | ||
|[[#Alectinib_monotherapy|Alectinib]] | |[[#Alectinib_monotherapy|Alectinib]] | ||
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===References=== | ===References=== | ||
# Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Jänne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, Iafrate AJ. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010 Oct 28;363(18):1693-703. [http://www.nejm.org/doi/full/10.1056/NEJMoa1006448 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014291/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20979469 PubMed] | # Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Jänne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, Iafrate AJ. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010 Oct 28;363(18):1693-703. [http://www.nejm.org/doi/full/10.1056/NEJMoa1006448 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014291/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20979469 PubMed] | ||
| − | ## '''Update:''' Camidge DR, Bang YJ, Kwak EL, Iafrate AJ, Varella-Garcia M, Fox SB, Riely GJ, Solomon B, Ou SH, Kim DW, Salgia R, Fidias P, Engelman JA, Gandhi L, Jänne PA, Costa DB, Shapiro GI, Lorusso P, Ruffner K, Stephenson P, Tang Y, Wilner K, Clark JW, Shaw AT. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol. 2012 Oct;13(10):1011-9. Epub 2012 Sep 4. [ | + | ## '''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://www.ncbi.nlm.nih.gov/pubmed/22954507 PubMed] |
# '''Retrospective:''' Shaw AT, Yeap BY, Solomon BJ, Riely GJ, Gainor J, Engelman JA, Shapiro GI, Costa DB, Ou SH, Butaney M, Salgia R, Maki RG, Varella-Garcia M, Doebele RC, Bang YJ, Kulig K, Selaru P, Tang Y, Wilner KD, Kwak EL, Clark JW, Iafrate AJ, Camidge DR. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol. 2011 Oct;12(11):1004-12. Epub 2011 Sep 18. [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://www.ncbi.nlm.nih.gov/pubmed/21933749 PubMed] | # '''Retrospective:''' Shaw AT, Yeap BY, Solomon BJ, Riely GJ, Gainor J, Engelman JA, Shapiro GI, Costa DB, Ou SH, Butaney M, Salgia R, Maki RG, Varella-Garcia M, Doebele RC, Bang YJ, Kulig K, Selaru P, Tang Y, Wilner KD, Kwak EL, Clark JW, Iafrate AJ, Camidge DR. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol. 2011 Oct;12(11):1004-12. Epub 2011 Sep 18. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328296/ link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3328296/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1214886 link to original article] [http://www.nejm.org/doi/suppl/10.1056/NEJMoa1214886/suppl_file/nejmoa1214886_appendix.pdf link to supplementary appendix] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23724913 PubMed] | # '''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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1214886 link to original article] [http://www.nejm.org/doi/suppl/10.1056/NEJMoa1214886/suppl_file/nejmoa1214886_appendix.pdf link to supplementary appendix] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23724913 PubMed] | ||
# '''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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1408440 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25470694 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1408440 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25470694 PubMed] | ||
## '''Supgroup 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. [http://ascopubs.org/doi/full/10.1200/JCO.2015.63.5888 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27022118 PubMed] | ## '''Supgroup 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. [http://ascopubs.org/doi/full/10.1200/JCO.2015.63.5888 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27022118 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. [ | + | # '''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://www.ncbi.nlm.nih.gov/pubmed/28501140 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1704795 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28586279 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1704795 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28586279 PubMed] | ||
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| − | |[ | + | |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30339-X/fulltext Shaw et al. 2017 (ASCEND-5)] |
|style="background-color:#1a9851"|Phase III | |style="background-color:#1a9851"|Phase III | ||
|[[Non-small_cell_lung_cancer#Docetaxel_monotherapy_2|Docetaxel]]<br> [[Non-small_cell_lung_cancer#Pemetrexed_monotherapy_3|Pemetrexed]] | |[[Non-small_cell_lung_cancer#Docetaxel_monotherapy_2|Docetaxel]]<br> [[Non-small_cell_lung_cancer#Pemetrexed_monotherapy_3|Pemetrexed]] | ||
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===References=== | ===References=== | ||
# '''Phase I:''' Shaw AT, Kim DW, Mehra R, Tan DS, Felip E, Chow LQ, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Lau YY, Goldwasser M, Boral AL, Engelman JA. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Mar 27;370(13):1189-97. [http://www.nejm.org/doi/full/10.1056/NEJMoa1311107 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079055/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24670165 PubMed] | # '''Phase I:''' Shaw AT, Kim DW, Mehra R, Tan DS, Felip E, Chow LQ, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Lau YY, Goldwasser M, Boral AL, Engelman JA. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Mar 27;370(13):1189-97. [http://www.nejm.org/doi/full/10.1056/NEJMoa1311107 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079055/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24670165 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. [ | + | # '''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://www.ncbi.nlm.nih.gov/pubmed/28602779 PubMed] |
# '''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://www.ncbi.nlm.nih.gov/pubmed/28729021 PubMed] | # '''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://www.ncbi.nlm.nih.gov/pubmed/28729021 PubMed] | ||
Revision as of 16:19, 20 May 2018
| Section editor | |
|---|---|
 |
Travis Osterman, DO, MS Nashville, TN Twitter: TravisOsterman |
Note: these are biomarker-specific regimens, please see the main NSCLC page for other regimens.
22 regimens on this page
27 variants on this page
|
Advanced or metastatic disease, ALK inhibitor-naive
Alectinib monotherapy
| back to top |
Variant #1, 300 mg BID
| Study | Evidence | Comparator | Efficacy |
|---|---|---|---|
| Seto et al. 2013 (AF-001JP) | Phase I/II | ||
| Hida et al. 2017 (J-ALEX) | Phase III (E) | Crizotinib | Superior PFS |
This is the PMDA-approved dose in Japan.
Chemotherapy
- Alectinib (Alecensa) 300 mg PO BID
Given indefinitely
Variant #2, 600 mg BID
| FDA-recommended dose |
| Study | Evidence | Comparator | Efficacy |
|---|---|---|---|
| Peters et al. 2017 (ALEX) | Phase III (E) | Crizotinib | Superior PFS |
Chemotherapy
- Alectinib (Alecensa) 600 mg PO BID
Given 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. link to original article contains verified protocol PubMed
- 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. link to original article link to PMC article 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. link to original articlecontains protocolPubMed
- 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. link to original article contains verified protocol PubMed
Ceritinib monotherapy
| back to top |
Variant #1, 450 mg/d with food
| FDA-recommended dose |
| Study | Evidence | Comparator |
|---|---|---|
| Cho et al. 2017 (ASCEND-8) | Randomized phase I | Ceritinib 750 mg/d |
Chemotherapy
- Ceritinib (Zykadia) 450 mg PO once per day with food
Continued indefinitely
Variant #2, 750 mg/d fasting
| Study | Evidence | Comparator | Efficacy |
|---|---|---|---|
| Soria et al. 2017 (ASCEND-4) | Phase III | Carboplatin & Pemetrexed Cisplatin & Pemetrexed |
Superior PFS |
| Cho et al. 2017 (ASCEND-8) | Randomized phase I | Ceritinib 450 mg/d | Not reported |
Chemotherapy
- Ceritinib (Zykadia) 750 mg PO once per day on an empty stomach
21-day cycles
References
- Phase I: Shaw AT, Kim DW, Mehra R, Tan DS, Felip E, Chow LQ, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Lau YY, Goldwasser M, Boral AL, Engelman JA. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Mar 27;370(13):1189-97. link to original article contains verified protocol link to PMC article 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. link to original article contains protocol PubMed
- 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. link to original article contains protocol PubMed
Crizotinib monotherapy
| back to top |
Variant #1, standard-dose
| FDA-recommended dose |
| Study | Evidence | Comparator | Efficacy |
|---|---|---|---|
| Kwak et al. 2010 | Phase I/II | ORR: 57% | |
| Shaw et al. 2013 (PROFILE 1007) | Phase III | Pemetrexed | Superior PFS |
| Docetaxel | Superior PFS | ||
| Solomon et al. 2014 (PROFILE 1014) | Phase III | Carboplatin & Pemetrexed Cisplatin & Pemetrexed |
Superior PFS |
| Hida et al. 2017 (J-ALEX) | Phase III | Alectinib | Inferior PFS |
| Peters et al. 2017 (ALEX) | Phase III | Alectinib | Inferior PFS |
Note: PROFILE 1007 used 21-day cycles, and crizotinib was similarly given 250 mg PO BID on all days.
Chemotherapy
- Crizotinib (Xalkori) 250 mg PO BID
28-day cycles
Variant #2, 200 mg BID
| FDA-recommended dose |
Note: this is the FDA-recommended dosing for "moderate" hepatic impairment.
Chemotherapy
- Crizotinib (Xalkori) 200 mg PO BID
Given indefinitely
Variant #3, 250 mg/d
| FDA-recommended dose |
Note: this is the FDA-recommended dosing for "severe" hepatic or renal impairment.
Chemotherapy
- Crizotinib (Xalkori) 250 mg PO once per day
Given indefinitely
References
- Kwak EL, Bang YJ, Camidge DR, Shaw AT, Solomon B, Maki RG, Ou SH, Dezube BJ, Jänne PA, Costa DB, Varella-Garcia M, Kim WH, Lynch TJ, Fidias P, Stubbs H, Engelman JA, Sequist LV, Tan W, Gandhi L, Mino-Kenudson M, Wei GC, Shreeve SM, Ratain MJ, Settleman J, Christensen JG, Haber DA, Wilner K, Salgia R, Shapiro GI, Clark JW, Iafrate AJ. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med. 2010 Oct 28;363(18):1693-703. link to original article contains verified protocol link to PMC article PubMed
- Update: Camidge DR, Bang YJ, Kwak EL, Iafrate AJ, Varella-Garcia M, Fox SB, Riely GJ, Solomon B, Ou SH, Kim DW, Salgia R, Fidias P, Engelman JA, Gandhi L, Jänne PA, Costa DB, Shapiro GI, Lorusso P, Ruffner K, Stephenson P, Tang Y, Wilner K, Clark JW, Shaw AT. Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study. Lancet Oncol. 2012 Oct;13(10):1011-9. Epub 2012 Sep 4. link to original article contains verified protocol link to PMC article PubMed
- Retrospective: Shaw AT, Yeap BY, Solomon BJ, Riely GJ, Gainor J, Engelman JA, Shapiro GI, Costa DB, Ou SH, Butaney M, Salgia R, Maki RG, Varella-Garcia M, Doebele RC, Bang YJ, Kulig K, Selaru P, Tang Y, Wilner KD, Kwak EL, Clark JW, Iafrate AJ, Camidge DR. Effect of crizotinib on overall survival in patients with advanced non-small-cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol. 2011 Oct;12(11):1004-12. Epub 2011 Sep 18. link to original article link to PMC article 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. link to original article link to supplementary appendix contains verified protocol 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. link to original article contains verified protocol PubMed
- Supgroup 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. link to original article 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. link to original articlecontains protocolPubMed
- 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. link to original article contains verified protocol PubMed
Advanced or metastatic disease, ALK inhibitor-exposed
Alectinib monotherapy
| back to top |
Regimen
| FDA-recommended dose |
| Study | Evidence | Efficacy |
|---|---|---|
| Ou et al. 2015 (NP28673) | Phase II | ORR: 50% (95% CI, 41-59) |
| Shaw et al. 2015 (NP28761) | Phase II | ORR: 48% (95% CI, 36–60) |
Patients in these trials had progression of disease on Crizotinib (Xalkori).
Chemotherapy
- Alectinib (Alecensa) 600 mg PO BID, to be taken within 30 minutes of eating
Given 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. link to original article contains verified protocol PubMed
- 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. link to original article link to PMC article contains protocol PubMed
Brigatinib monotherapy
Brigatinib (Alunbrig) for advanced or metastatic ALK-positive non-small cell lung cancer
Ceritinib monotherapy
| back to top |
Variant #1, 450 mg/d with food
| FDA-recommended dose |
| Study | Evidence | Comparator |
|---|---|---|
| Cho et al. 2017 (ASCEND-8) | Randomized phase I | Ceritinib 750 mg/d |
Chemotherapy
- Ceritinib (Zykadia) 450 mg PO once per day with food
Continued indefinitely
Variant #2, 750 mg/d fasting
| Study | Evidence | Comparator | Efficacy |
|---|---|---|---|
| Shaw et al. 2017 (ASCEND-5) | Phase III | Docetaxel Pemetrexed |
Superior PFS |
| Cho et al. 2017 (ASCEND-8) | Randomized phase I | Ceritinib 450 mg/d | Not reported |
Chemotherapy
- Ceritinib (Zykadia) 750 mg PO once per day on an empty stomach
21-day cycles
References
- Phase I: Shaw AT, Kim DW, Mehra R, Tan DS, Felip E, Chow LQ, Camidge DR, Vansteenkiste J, Sharma S, De Pas T, Riely GJ, Solomon BJ, Wolf J, Thomas M, Schuler M, Liu G, Santoro A, Lau YY, Goldwasser M, Boral AL, Engelman JA. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Mar 27;370(13):1189-97. link to original article contains verified protocol link to PMC article 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. link to original articlecontains protocolPubMed
- 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. link to original article contains protocol PubMed