WEEKLY IMPORTANT NEWS FROM MEDSCAPE AND OTHER SOURCES
Σάββατο, 3 Ιουνίου 2017
ALECTINIB BETTER THAN CRIZOTINIB
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.
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.
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.
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.