In an interim analysis of the phase III ELEVATE trial reported in The New England Journal of Medicine, Yue et al found that patients with completely resected ALK-positive non–small cell lung cancer (NSCLC) who received adjuvant ensartinib experienced significantly longer disease-free survival than those receiving placebo. The investigators conducted the study to determine whether the second-generation ALK inhibitor could improve outcomes after surgery and adjuvant chemotherapy in patients with resectable ALK-positive disease.
Study Details
The double-blind, placebo-controlled trial randomly assigned 274 patients with completely resected stage IB to IIIB ALK-positive NSCLC in a 1:1 ratio to receive oral ensartinib at 225 mg once daily or placebo for up to 24 months following surgery and any planned adjuvant platinum-based chemotherapy. The primary endpoint was investigator-assessed disease-free survival among patients with stage II to IIIB disease. The median follow-up for disease-free survival was 24 months.
Key Findings
Among the 205 patients with stage II to IIIB disease, disease recurrence or death occurred in 12 patients treated with ensartinib compared with 46 receiving placebo. At 24 months, 86.4% of patients in the ensartinib group remained alive and disease-free compared with 53.5% in the placebo group (hazard ratio [HR] = 0.20, 95% confidence interval [CI] = 0.11–0.38, P < .001).
Similar findings were observed in the overall study population, with 24-month disease-free survival rates of 87.3% and 57.2%, respectively (HR = 0.20, 95% CI = 0.10–0.37, P < .001). Recurrence occurred in 8.8% of patients receiving ensartinib vs 33.6% receiving placebo. Overall survival data remain immature, with only three deaths reported across both treatment groups at the time of analysis.
Grade 3 or higher adverse events occurred in 35.8% of patients receiving ensartinib compared with 18.2% receiving placebo. The most common grade 3 or higher adverse events in the ensartinib group were rash (14.6%) and pneumonia (5.1%). Dose interruptions and dose reductions were more frequent with ensartinib, although treatment discontinuation because of adverse events remained uncommon, occurring in only 2.2% of patients. No new safety signals were identified.
The investigators concluded: “Among patients with completely resected stage IB to IIIB ALK-positive NSCLC, the percentage of patients who were alive and disease-free at 24 months was significantly higher with ensartinib than with placebo.”
Changli Wang, MD, of the Department of Lung Cancer, Tianjin Medical University Institute and Hospital, Tianjin, China, and You Lu, MD, of Cancer Center, West China Hospital, Sichuan University, Chengdu, China, are the corresponding authors for the New England Journal of Medicine article.
DISCLOSURE: The study was supported by Betta Pharmaceuticals. For full disclosures of the study authors, visit nejm.org.
