Study Finds Crizotinib Does Not Extend Disease-Free Survival in Early-Stage ALK+ Lung Cancer

Recent clinical trial results presented at the 2025 World Conference on Lung Cancer reveal that crizotinib, a targeted therapy approved for advanced ALK-positive non-small cell lung cancer (NSCLC), does not provide a benefit in preventing disease recurrence when used as an adjuvant treatment in patients with early-stage, resected ALK+ NSCLC. The Phase II E4512 trial studied patients with stage IIA–IIIB disease, confirmed by FISH, IHC, or NGS, who underwent surgery with clean margins and received no prior ALK inhibitor therapy.

Participants were randomized to either observation or receive crizotinib at 250 mg twice daily for up to two years, with the primary goal of assessing disease-free survival (DFS). The trial enrolled 166 patients between 2014 and 2024, with most remaining confirmed ALK+ upon central testing. Results showed no significant difference in DFS: median DFS was approximately 73 months for the crizotinib group versus 75 months for observation, indicating no meaningful clinical benefit. Overall survival data were immature, with medianOS not reached in either group.

Safety data indicated that about one-third of patients experienced grade 3 adverse events, commonly diarrhea and edema, with some requiring dose reductions or treatment discontinuation. Notably, 4% of patients experienced grade 4 events such as stroke.

The trial was subsequently halted after the FDA approved adjuvant alectinib for this patient population. Dr. David Gerber and colleagues concluded that adjuvant crizotinib does not improve disease-free survival in resected early-stage ALK+ NSCLC, emphasizing the need for alternative strategies in this setting.

This landmark study highlights the importance of evidence-based approaches in the management of early-stage lung cancer and guides future research efforts.

(Source: https://medicalxpress.com/news/2025-09-crizotinib-disease-free-survival-resected.html)