This phase 3 RCT (E4512) evaluated adjuvant crizotinib 250 mg twice daily vs. observation/placebo for up to 2 years in patients with surgically resected, early-stage (≥4 cm or node-positive) ALK-positive NSCLC, with disease-free survival (DFS) as the primary endpoint in the centrally confirmed ALK-positive ITT population.
After a median follow-up of 65.7 months, adjuvant crizotinib did **not** improve DFS vs. observation (median DFS 74.6 vs. 106.2 months; HR 1.08 [95% CI 0.61–1.90]; p=0.80). Grade ≥3 adverse events occurred in 58% of crizotinib-treated patients, most commonly diarrhoea (10%), oedema (5%), and hypertension (5%).
- Trial enrolled only 166 of 168 planned patients and was stopped early due to FDA approval of adjuvant alectinib, leaving it underpowered. - The protocol shifted from double-blind placebo to open-label observation during the trial, introducing potential performance bias. - The population was predominantly White (79%) and female (65%), limiting generalizability.
Crizotinib should **not** be used as adjuvant therapy for resected ALK-positive NSCLC — it confers no DFS benefit and carries meaningful toxicity. Adjuvant alectinib (FDA-approved) remains the standard of care for this population.
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