Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial
- PMID: 28501140
- DOI: 10.1016/S0140-6736(17)30565-2
Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial
Abstract
Background: Alectinib, a potent, highly selective, CNS-active inhibitor of anaplastic lymphoma kinase (ALK), showed promising efficacy and tolerability in the single-arm phase 1/2 AF-001JP trial in Japanese patients with ALK-positive non-small-cell lung cancer. Given those promising results, we did a phase 3 trial to directly compare the efficacy and safety of alectinib and crizotinib.
Methods: J-ALEX was a randomised, open-label, phase 3 trial that recruited ALK inhibitor-naive Japanese patients with ALK-positive non-small-cell lung cancer, who were chemotherapy-naive or had received one previous chemotherapy regimen, from 41 study sites in Japan. Patients were randomly assigned (1:1) via an interactive web response system using a permuted-block method stratified by Eastern Cooperative Oncology Group performance status, treatment line, and disease stage to receive oral alectinib 300 mg twice daily or crizotinib 250 mg twice daily until progressive disease, unacceptable toxicity, death, or withdrawal. The primary endpoint was progression-free survival assessed by an independent review facility. The efficacy analysis was done in the intention-to-treat population, and safety analyses were done in all patients who received at least one dose of the study drug. The study is ongoing and patient recruitment is closed. This study is registered with the Japan Pharmaceutical Information Center (number JapicCTI-132316).
Findings: Between Nov 18, 2013, and Aug 4, 2015, 207 patients were recruited and assigned to the alectinib (n=103) or crizotinib (n=104) groups. At data cutoff for the second interim analysis, 24 patients in the alectinib group had discontinued treatment compared with 61 in the crizotinib group, mostly due to lack of efficacy or adverse events. At the second interim analysis (data cutoff date Dec 3, 2015), an independent data monitoring committee determined that the primary endpoint of the study had been met (hazard ratio 0·34 [99·7% CI 0·17-0·71], stratified log-rank p<0·0001) and recommended an immediate release of the data. Median progression-free survival had not yet been reached with alectinib (95% CI 20·3-not estimated) and was 10·2 months (8·2-12·0) with crizotinib. Grade 3 or 4 adverse events occurred at a greater frequency with crizotinib (54 [52%] of 104) than alectinib (27 [26%] of 103). Dose interruptions due to adverse events were also more prevalent with crizotinib (77 [74%] of 104) than with alectinib (30 [29%] of 103), and more patients receiving crizotinib (21 [20%]) than alectinib (nine [9%]) discontinued the study drug because of an adverse event. No adverse events with a fatal outcome occurred in either treatment group.
Interpretation: These results provide the first head-to-head comparison of alectinib and crizotinib and have the potential to change the standard of care for the first-line treatment of ALK-positive non-small-cell lung cancer. The dose of alectinib (300 mg twice daily) used in this study is lower than the approved dose in countries other than Japan; however, this limitation is being addressed in the ongoing ALEX study.
Funding: Chugai Pharmaceutical Co, Ltd.
Copyright © 2017 Elsevier Ltd. All rights reserved.
Comment in
-
J-ALEX: alectinib versus crizotinib in ALK-positive lung cancer.Lancet. 2017 Jul 1;390(10089):3-4. doi: 10.1016/S0140-6736(17)31074-7. Epub 2017 May 10. Lancet. 2017. PMID: 28501139 No abstract available.
-
The J-ALEX trial-is frontline alectinib a new standard of care?J Thorac Dis. 2017 Aug;9(8):2242-2245. doi: 10.21037/jtd.2017.06.134. J Thorac Dis. 2017. PMID: 28932515 Free PMC article. No abstract available.
-
A few pills twice a day keep ALK-positive non-small-cell lung cancer at bay.J Thorac Dis. 2017 Aug;9(8):2311-2314. doi: 10.21037/jtd.2017.07.76. J Thorac Dis. 2017. PMID: 28932533 Free PMC article. No abstract available.
-
Moving more potent and less toxic options to the frontline in the management of advanced lung cancer.J Thorac Dis. 2017 Sep;9(9):2812-2818. doi: 10.21037/jtd.2017.08.79. J Thorac Dis. 2017. PMID: 29221246 Free PMC article. No abstract available.
-
Alectinib in untreated anaplastic lymphoma kinase-positive non-small cell lung cancer.Ann Transl Med. 2017 Dec;5(23):460. doi: 10.21037/atm.2017.09.05. Ann Transl Med. 2017. PMID: 29285493 Free PMC article. No abstract available.
-
J-ALEX trial will crown alectinib as the standard choice for anaplastic lymphoma kinase positive untreated non-small cell lung cancer patients?J Thorac Dis. 2018 Jan;10(1):106-108. doi: 10.21037/jtd.2017.12.76. J Thorac Dis. 2018. PMID: 29600033 Free PMC article. No abstract available.
-
Is alectinib the new first line therapy in ALK-rearranged advanced non-small cell lung cancer?J Thorac Dis. 2018 Jul;10(Suppl 18):S2130-S2132. doi: 10.21037/jtd.2018.06.45. J Thorac Dis. 2018. PMID: 30123541 Free PMC article. No abstract available.
-
(J)ALEX the great: a new era in the world of ALK inhibitors.J Thorac Dis. 2018 Jul;10(Suppl 18):S2138-S2143. doi: 10.21037/jtd.2018.06.142. J Thorac Dis. 2018. PMID: 30123543 Free PMC article. No abstract available.
Similar articles
-
Alectinib versus Crizotinib in Untreated ALK-Positive Non-Small-Cell Lung Cancer.N Engl J Med. 2017 Aug 31;377(9):829-838. doi: 10.1056/NEJMoa1704795. Epub 2017 Jun 6. N Engl J Med. 2017. PMID: 28586279 Clinical Trial.
-
Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study.Lancet Oncol. 2014 Sep;15(10):1119-28. doi: 10.1016/S1470-2045(14)70362-6. Epub 2014 Aug 18. Lancet Oncol. 2014. PMID: 25153538 Clinical Trial.
-
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. doi: 10.1016/S1470-2045(15)00488-X. Epub 2015 Dec 19. Lancet Oncol. 2016. PMID: 26708155 Free PMC article. Clinical Trial.
-
Alectinib for ALK-positive non-small-cell lung cancer.Expert Rev Clin Pharmacol. 2016 Aug;9(8):1005-13. doi: 10.1080/17512433.2016.1195262. Epub 2016 Jun 21. Expert Rev Clin Pharmacol. 2016. PMID: 27232673 Review.
-
Alectinib: A Review in Advanced, ALK-Positive NSCLC.Drugs. 2018 Aug;78(12):1247-1257. doi: 10.1007/s40265-018-0952-0. Drugs. 2018. PMID: 30030733 Review.
Cited by
-
Alectinib Versus Crizotinib in Asian Patients With Treatment-Naïve Advanced ALK-Positive NSCLC: Five-Year Update From the Phase 3 ALESIA Study.JTO Clin Res Rep. 2024 Jun 27;5(9):100700. doi: 10.1016/j.jtocrr.2024.100700. eCollection 2024 Sep. JTO Clin Res Rep. 2024. PMID: 39282663 Free PMC article.
-
Gingival Metastasis of ALK Rearranged Non-Small Cell Lung Cancer.Case Rep Oncol. 2019 Feb 20;12(1):171-177. doi: 10.1159/000497481. eCollection 2019 Jan-Apr. Case Rep Oncol. 2019. PMID: 39263342 Free PMC article.
-
Efficacy of ALK inhibitors in Asian patients with ALK inhibitor-naïve advanced ALK-positive non-small cell lung cancer: a systematic review and network meta-analysis.Transl Lung Cancer Res. 2024 Aug 31;13(8):2015-2022. doi: 10.21037/tlcr-24-604. Epub 2024 Aug 28. Transl Lung Cancer Res. 2024. PMID: 39263024 Free PMC article.
-
Real-World Treatment and Outcomes in ALK-Rearranged NSCLC: Results From a Large U.S.-Based Database.JTO Clin Res Rep. 2024 Mar 7;5(8):100662. doi: 10.1016/j.jtocrr.2024.100662. eCollection 2024 Aug. JTO Clin Res Rep. 2024. PMID: 39157676 Free PMC article.
-
Expert Consensus on the Management of Adverse Events of Lorlatinib in the Treatment of ALK+ Advanced Non-small Cell Lung Cancer.Clin Drug Investig. 2024 Aug;44(8):553-576. doi: 10.1007/s40261-024-01379-7. Epub 2024 Jul 31. Clin Drug Investig. 2024. PMID: 39085682 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous