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.

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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.”


  1. 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]