Crizotinib (ALK TKI) Fails to Improve DFS as Adjuvant Therapy in Resected ALK+ NSCLC (E4512)

Crizotinib is a first-generation oral ALK tyrosine kinase inhibitor (TKI) evaluated as adjuvant therapy in the ECOG-ACRIN E4512 Phase 3 trial (NCT02201992) versus observation in resected early-stage ALK+ NSCLC (tumor ≥4cm and/or node-positive; ECOG 0–1), with treatment planned for up to 2 years (n=166 enrolled; centrally confirmed ALK+ n=153). At median 65.7 months’ follow-up, DFS was not improved with crizotinib (median DFS 74.6 vs 106.2 months; HR 1.08; p=0.80), while grade ≥3 AEs occurred in 58% (notably grade ≥3 diarrhea 10%, edema 5%, hypertension 5%) and serious AEs in 27%. In practice, this underperforms current adjuvant ALK standard-of-care alectinib—FDA-approved April 18, 2024 based on ALINA, where alectinib markedly prolonged DFS vs platinum chemo (overall population HR 0.24; median DFS not reached vs 41.3 months).