(Barcelona, Spain September 7, 2025, 10:45 a.m. CEST / UTC +2 ) — Crizotinib, an approved treatment for advanced ALK-positive (ALK+) non-small cell lung cancer (NSCLC), did not improve disease-free survival (DFS) when given as adjuvant therapy in patients with surgically resected early-stage ALK+ NSCLC, according to results from the Phase 3 E4512 trial presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC).
The trial, conducted within the ALCHEMIST clinical trials program, enrolled patients with resected stage IIA–IIIB (AJCC 8th edition) ALK+ NSCLC confirmed by FISH, IHC, or NGS. Eligible patients had negative surgical margins, an ECOG performance status of 0–1, and no prior ALK inhibitor therapy. Adjuvant chemotherapy and post-operative radiation therapy were permitted.
David Gerber, MD, a medical oncologist at the UT Southwestern Harold C. Simmons Comprehensive Cancer Center, and colleagues randomized patients to receive observation or crizotinib 250 mg twice daily for up to two years, or until disease recurrence or unacceptable toxicity. The primary endpoint was DFS, with secondary endpoints of overall survival (OS) and safety.
Between August 2014 and May 2024, 166 patients (of 168 planned) were enrolled (92% confirmed centrally as ALK+). Enrollment was stopped after the U.S. Food and Drug Administration approved adjuvant alectinib for resected ALK+ NSCLC.
At a median follow-up of 58.3 months the study found that:
- Median DFS was 72.8 months for crizotinib vs. 75.1 months for observation (HR 1.06; 90% CI, 0.63–1.77; P=0.86).
- Median OS was not reached in either arm (HR 0.49; 90% CI, 0.18–1.37; P=0.26).
- Grade 3 treatment-related adverse events occurred in 34% of patients receiving crizotinib, most commonly diarrhea (6%) and edema (4%); one patient experienced a grade 4 event (stroke).
- 22% of patients required dose reductions and 25% discontinued treatment due to toxicity.
"Adjuvant crizotinib does not prolong disease-free survival in resected ALK+ NSCLC," said Dr. Gerber.
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