Alectinib prolongs progression-free survival (PFS) with less toxicity compared with crizotinib among Japanese patients with ALK-positive non–small-cell lung cancer (NSCLC), according to the results of the J-ALEX study published in The Lancet.1
Alectinib is a selective ALK inhibitor with systemic and central nervous system activity that demonstrated promising results in a phase 1/2 trial. This study aimed to evaluate the efficacy and safety of alectinib in the first head-to-head trial of ALK inhibitors.
The open-label, phase 3 J-ALEX trial randomly assigned 207 Japanese patients with ALK-positive NSCLC to receive 300 mg of alectinib twice daily or 250 mg of crizotinib twice daily until disease progression, unacceptable toxicity, death, or study withdrawal.
The median age was 60 at baseline and the majority of patients had stage IV disease. Study treatment was the first-line therapy for 64% of patients; brain metastases were present in 16% and 30% of patients in the alectinib and crizotinib arms, respectively.
The objective response rate was 92% with alectinib compared with 79% with crizotinib, with a time to response of 1 month for both agents. Complete response was achieved by 2% of patients in both arms, with 89% and 77% experiencing a partial response in the alectinib and crizotinib groups, respectively.
Alectinib significantly prolonged PFS with the median PFS not yet reached compared with 10.2 months (95% CI, 8.2-12.0) with crizotinib (hazard ratio [HR], 0.34; 99.7% CI, 0.17-0.71; log-rank P < .0001).
Patients receiving alectinib in the first-line experienced the greatest benefit (not reached vs 10.2 months; HR, 0.31; 95% CI, 0.17-0.57), but second-line treatment was also significantly better than second-line crizotinib (20.3 vs 8.2 months; HR, 0.40; 95% CI, 0.19-0.87).
Overall survival data are not yet mature.
The most common adverse event (AE) was constipation and nasopharyngitis with alectinib. The rate of grade 3 to 4 AEs was higher with crizotinib compared with alectinib (52% vs 26%, respectively). Dose interruptions were also more common with crizotinib (74% vs 29%, respectively).
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According to the authors, the results of this study “have the potential to change the standard of care for the first-line treatment of patients with ALK-positive NSCLC.”
- Hida T, Nokihara H, Kondo M, et al. Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial. Lancet. 2017 May 10. doi: 10.1016/S0140-6736(17)30565-2 [Epub ahead of print]