Difference between revisions of "Non-small cell lung cancer, ALK-positive"
Jump to navigation
Jump to search
Warner-admin (talk | contribs) m (Text replacement - "Comparative Efficacy" to "Comparative Efficacy") |
Warner-admin (talk | contribs) m (Text replacement - "http://ascopubs.org" to "https://ascopubs.org") |
||
| Line 69: | Line 69: | ||
===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. [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] | # '''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. [ | + | ## '''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://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. [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] | # '''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] | ||
## '''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://www.sciencedirect.com/science/article/pii/S016950021830343X link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/29858024 PubMed] | ## '''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://www.sciencedirect.com/science/article/pii/S016950021830343X link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/29858024 PubMed] | ||
| Line 246: | Line 246: | ||
## '''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://www.ncbi.nlm.nih.gov/pubmed/28701030 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://www.ncbi.nlm.nih.gov/pubmed/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://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. [https://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. [ | + | ## '''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. [https://ascopubs.org/doi/full/10.1200/JCO.2015.63.5888 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/28701030 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://www.ncbi.nlm.nih.gov/pubmed/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. [ | + | ## '''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://ascopubs.org/doi/full/10.1200/JCO.2017.77.4794 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/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://www.ncbi.nlm.nih.gov/pubmed/28501140 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://www.ncbi.nlm.nih.gov/pubmed/28501140 PubMed] | ||
## '''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://www.sciencedirect.com/science/article/pii/S016950021830343X link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/29858024 PubMed] | ## '''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://www.sciencedirect.com/science/article/pii/S016950021830343X link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/29858024 PubMed] | ||
| Line 273: | Line 273: | ||
!style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 25%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
| − | ||[ | + | ||[https://ascopubs.org/doi/full/10.1200/JCO.2015.63.9443 Ou et al. 2015 (NP28673)] |
|style="background-color:#91cf61"|Phase II | |style="background-color:#91cf61"|Phase II | ||
| | | | ||
| Line 295: | Line 295: | ||
===References=== | ===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. [ | + | # '''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. [https://ascopubs.org/doi/full/10.1200/JCO.2015.63.9443 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26598747 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] --> | <!-- # '''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://www.ncbi.nlm.nih.gov/pubmed/26708155 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. [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://www.ncbi.nlm.nih.gov/pubmed/26708155 PubMed] | ||
Revision as of 14:58, 23 June 2019
| Section editor | |
|---|---|
 |
Travis Osterman, DO, MS Vanderbilt University Nashville, TN  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 twice per day
| Study | Evidence | Comparator | Comparative 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 twice per day
Continued indefinitely
Variant #2, 600 mg twice per day
| FDA-recommended dose |
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Peters et al. 2017 (ALEX) | Phase III (E) | Crizotinib | Superior PFS |
Chemotherapy
- 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. 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
- 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. link to SD article 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. link to original article contains verified protocol PubMed
- 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. link to original article PubMed
Brigatinib monotherapy
| back to top |
Regimen
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Camidge et al. 2018 (ALTA-1L) | Phase III (E) | Crizotinib | Superior PFS |
Chemotherapy
- 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. link to original article contains protocol PubMed
Ceritinib monotherapy
| back to top |
Variant #1, 450 mg/day 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/day fasting
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Shaw et al. 2014 (ASCEND-1) | Phase I, >20 pts in this dosing cohort | ||
| Soria et al. 2017 (ASCEND-4) | Phase III (E) | 1. Carboplatin & Pemetrexed 2. 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
- 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. link to original article 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, 250 mg/day
| 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
Continued indefinitely
Variant #2, 400 mg/day
| FDA-recommended dose |
Note: this is the FDA-recommended dosing for "moderate" hepatic impairment.
Chemotherapy
- Crizotinib (Xalkori) 200 mg PO twice per day
Continued indefinitely
Variant #3, 500 mg/day
| FDA-recommended dose |
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Kwak et al. 2010 | Phase I/II | ORR: 57% | |
| Shaw et al. 2013 (PROFILE 1007) | Phase III (E) | 1. Pemetrexed | Superior PFS |
| 2. Docetaxel | Superior PFS | ||
| Solomon et al. 2014 (PROFILE 1014) | Phase III (E) | 1. Carboplatin & Pemetrexed 2. Cisplatin & Pemetrexed |
Superior PFS |
| Hida et al. 2017 (J-ALEX) | Phase III (C) | Alectinib | Inferior PFS |
| Peters et al. 2017 (ALEX) | Phase III (C) | Alectinib | Inferior PFS |
| Camidge et al. 2018 (ALTA-1L) | Phase III (C) | Brigatinib | Inferior PFS |
Note: PROFILE 1007 used 21-day cycles, and crizotinib was similarly given 250 mg PO twice per day on all days.
Chemotherapy
- Crizotinib (Xalkori) 250 mg PO twice per day
28-day cycles
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
- 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. link to original article link to PMC article 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
- 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. link to original article link to PMC article 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. 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
- 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. link to SD article 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. link to original article contains verified protocol PubMed
- 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. link to original article PubMed
- 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. link to original article contains protocol PubMed
Advanced or metastatic disease, ALK inhibitor-exposed
Alectinib monotherapy
| back to top |
Regimen
| FDA-recommended dose |
| Study | Evidence | Comparator | Comparative 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) | |
| Novello et al. 2018 (ALUR) | Phase III (E) | Docetaxel Pemetrexed |
Superior PFS |
Chemotherapy
- 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. 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
- 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. 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/day 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/day fasting
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Shaw et al. 2014 (ASCEND-1) | Phase I, >20 pts in this dosing cohort | ||
| Shaw et al. 2017 (ASCEND-5) | Phase III (E) | 1. Docetaxel 2. 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
- 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. link to original article 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
Lorlatinib monotherapy
| back to top |
Regimen
| FDA-recommended dose |
| Study | Evidence |
|---|---|
| Shaw et al. 2017 (B7461001) | Phase I, >20 pts in this subgroup |
Chemotherapy
- Lorlatinib (Lorbrena) 100 mg PO once per day
Continued indefinitely
References
- Phase 1: 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. link to original article contains protocol PubMed