Ensartinib After Resection in Alk-Positive NSCLC

Key Takeaways

• In stage II to IIIB disease, ensartinib was associated with a hazard ratio of 0.20 for recurrence or death versus placebo.
• A similar disease-free survival advantage was reported in the overall randomized population at 24 months.
• Grade 3 or higher adverse events were more common with ensartinib, rash was the most common severe event, and overall survival data were immature.

Adjuvant ensartinib was associated with higher 24-month disease-free survival than placebo after complete resection in ALK-positive NSCLC, according to a phase 3 NEJM trial.

The phase 3 trial used a double-blind, randomized design and assigned 274 patients, 137 per group, after adjuvant chemotherapy for completely resected ALK-positive stage IB to IIIB NSCLC. Patients were randomly assigned 1:1 to ensartinib 225 mg once daily or placebo for 24 months. The primary endpoint was disease-free survival in stage II to IIIB disease, and disease-free survival in the overall population was a key secondary endpoint. This prespecified hierarchy distinguished the primary analysis population from the broader randomized cohort.

In the primary stage II to IIIB population, the hazard ratio for disease recurrence or death was 0.20. The 95% confidence interval was 0.11 to 0.38, and the P value was less than 0.001. At the same 24-month landmark, the alive-and-disease-free proportions were 86.4% with ensartinib and 53.5% with placebo. Together, these findings defined the primary comparison. The primary endpoint favored ensartinib.

The key secondary analysis in the overall randomized population also favored ensartinib. At 24 months, disease-free survival was 87.3% with ensartinib and 57.2% with placebo. The hazard ratio was 0.20, with a 95% confidence interval of 0.10 to 0.37 and a P value less than 0.001. This showed a similar disease-free survival pattern in the broader randomized population. Overall survival data were immature.

Grade 3 or higher adverse events occurred in 35.8% of patients who received ensartinib and 18.2% of those who received placebo. Rash was the most common grade 3 or higher adverse event with ensartinib. Across the reported 24-month analyses, ensartinib was associated with significantly higher disease-free survival than placebo.