Japanese Phase III Trial of Alectinib vs Crizotinib in ALK-Positive NSCLC

Key Points

  • In ALK inhibitor–naive patients with ALK-positive NSCLC, alectinib improved progression-free survival vs crizotinib.
  • Improvement was observed in both first- and second-line settings.

The Japanese phase III J-ALEX trial has shown improved progression-free survival with alectinib (Alecensa) vs crizotinib (Xalkori) in ALK inhibitor–naive patients with ALK-positive non–small-cell lung cancer (NSCLC). Results were reported by Hida et al in The Lancet.

Study Details

In the open-label trial, 207 patients who had received no or one prior chemotherapy regimen were randomized between November 2013 and August 2015 to receive alectinib at 300 mg twice daily (n = 103) or crizotinib at 250 mg twice daily (n = 104) until progressive disease or unacceptable toxicity. Randomization was stratified by Eastern Cooperative Oncology Group performance status, treatment line, and disease stage.

The primary endpoint was progression-free survival on independent review in the intention-to-treat population. The study is ongoing, and patient recruitment is closed.

Progression-Free Survival

At second interim analysis (data cutoff in December 2015), an independent data monitoring committee determined that the primary endpoint had been met. After median follow-up of approximately 12 months, median progression-free survival was not reached (95% confidence interval [CI] = 20.3 months to not estimable) in the alectinib group vs 10.2 months (95% CI = 8.2–12.0 months) in the crizotinib group (hazard ratio [HR] = 0.34, P < .0001).

Median progression-free survival was not reached vs 10.2 months in the first-line setting (64% of patients; HR = 0.31, 95% CI = 0.17–0.57) and 20.3 months vs 8.2 months in the second-line setting (34% of patients; HR = 0.40, 95% CI = 0.19–0.87). The benefit of alectinib was apparent among both patients with postoperative recurrence (24% of patients; HR = 0.55, 95% CI = 0.20–1.48) and those with stage IIIB or IV disease (76% of patients; HR = 0.30, 95% CI = 0.18–0.52). Overall survival data are immature.

Adverse Events

Grade 3 or 4 adverse events occurred in 26% of the alectinib group vs 52% of the crizotinib group. Adverse events led to treatment interruption in 29% vs 74% and to treatment discontinuation in 9% vs 20%. Interstitial lung disease occurred in 8% of patients in both groups. No deaths due to adverse events were reported.

The investigators concluded: “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.”

The study was funded by Chugai Pharmaceutical Co, Ltd.

Tomohide Tamura, MD, of St. Luke’s International Hospital, Chuo-ku, Tokyo, is the corresponding author of The Lancet article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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