Crizotinib Shows No Benefit for Disease-Free Survival in Early Stage ALK+ NSCLC

Recent findings from a Phase II trial have revealed that crizotinib, a medication previously approved for treating advanced ALK-positive non-small cell lung cancer (NSCLC), does not enhance disease-free survival (DFS) when used as adjuvant therapy in patients with early-stage surgically resected ALK+ NSCLC. These results were presented at the 2025 World Conference on Lung Cancer organized by the International Association for the Study of Lung Cancer (IASLC).

The trial was part of the broader ALCHEMIST clinical trials initiative and included patients diagnosed with resected stage IIA to IIIB ALK+ NSCLC, confirmed through methods such as fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), or next-generation sequencing (NGS). Eligible subjects were required to have negative surgical margins, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and no prior exposure to ALK inhibitors. Participants could also receive adjuvant chemotherapy and post-operative radiation therapy.

Led by a team from the UT Southwestern Harold C. Simmons Comprehensive Cancer Center, the study randomized participants to either crizotinib treatment--at a dosage of 250 mg twice daily for a maximum of two years--or observation. The primary focus was on DFS, with secondary goals including overall survival (OS) and safety measures.

Between August 2014 and May 2024, the trial enrolled 166 patients out of an intended 168, with 92% of these patients confirmed as ALK+. Enrollment was halted following the U.S. Food and Drug Administration's approval of alectinib as an adjuvant treatment for resected ALK+ NSCLC.

At a median follow-up duration of 58.3 months, the study reported the following outcomes:

• Median DFS was observed at 72.8 months for the crizotinib group compared to 75.1 months for the observation group (Hazard Ratio [HR] 1.06; 90% Confidence Interval [CI], 0.63-1.77; P=0.86).
• Median OS had not been reached in either treatment group (HR 0.49; 90% CI, 0.18-1.37; P=0.26).
• Adverse events classified as grade 3 occurred in 34% of patients on crizotinib, with diarrhea (6%) and edema (4%) being the most frequent, while one patient reported a grade 4 event (stroke).
• 22% of patients experienced dose reductions, and 25% discontinued treatment due to adverse effects.

The findings indicate that the use of crizotinib as an adjuvant treatment does not prolong disease-free survival in patients with resected ALK+ NSCLC.