Adjuvant erlotinib (EGFR TKI) fails to improve OS after resection in EGFR-mutant NSCLC

Erlotinib is a first-generation oral EGFR tyrosine kinase inhibitor (exon19 del/L858R) tested in the ALCHEMIST/Alliance A081105 randomized Phase 3 adjuvant trial (NCT02193282) in completely resected stage IB (≥4cm), II, or IIIA non-squamous NSCLC. In the per-protocol, centrally confirmed EGFR-mutant population (n=364; 108 OS events), erlotinib 150mg daily for up to 2 years did not improve OS vs placebo/observation (HR 0.89, 95% CI 0.59–1.34; 1-sided p=0.29), with 5-year OS 78.6% vs 77.9%; DFS trended better in mITT (n=379) with median 68 vs 50 months (HR 0.74, 95% CI 0.55–1.01) but with substantial tolerability/feasibility issues (median treatment 16 months; only 37% completed planned 2 years; grade ≥3 AEs in 39%). Versus current SOC adjuvant osimertinib (3rd-gen EGFR TKI), which does show an OS benefit in resected stage IB–IIIA EGFR-mutant NSCLC (stage II–IIIA: OS HR ~0.49; 5-year OS ~85% vs ~73%), these data essentially close the door on erlotinib for OS impact in the adjuvant setting (and highlight how much adherence matters in “long-course” adjuvant targeted therapy).