Nivolumab (PD-1) adjuvant therapy fails to extend DFS after NSCLC resection + chemo (EA5142/ALCHEMIST)

Nivolumab is an anti–PD-1 checkpoint inhibitor tested as 1 year of adjuvant therapy (480 mg IV q4w) after surgery and completion of standard adjuvant chemotherapy and/or PORT in resected high-risk NSCLC (tumor ≥4cm and/or N1/2; EGFR/ALK-sensitizing–negative adenocarcinoma plus squamous; n=935 randomized). With median follow-up 72.6 months, DFS was not improved in ITT (median 71.3 vs 68.8 months; HR 0.97, p=0.78) nor in PD-L1≥50% (median 89.8 vs 78.5 months; HR 0.86, p=0.43); excluding new primary lung cancers didn’t change the null result (ITT HR 0.97). Safety was non-trivial for an adjuvant setting: grade 3–5 treatment-related toxicity 25% and discontinuation due to AEs 29% (median treatment duration 9.4 months)—a tough tradeoff versus observation, and notably weaker than the DFS benefit seen with other adjuvant PD-(L)1 approaches in similar post-op populations (e.g., pembrolizumab HR 0.76 in KEYNOTE-091; atezolizumab HR 0.66 in PD-L1≥1% stage II–IIIA in IMpower010). Trial: NCT02595944.