Nivolumab (PD-1 inhibitor) Fails to Improve DFS vs Observation After NSCLC Resection

Nivolumab is an anti–PD-1 checkpoint inhibitor tested as adjuvant therapy after upfront surgery (and after completion of planned adjuvant chemotherapy and/or radiotherapy) in the ECOG-ACRIN EA5142 Phase 3 trial (NCT02595944) in resected NSCLC ≥4cm and/or N1/N2, excluding sensitizing EGFR/ALK alterations in nonsquamous histology. At median follow-up 72.6 months (data cutoff December 2025), adjuvant nivolumab 480mg Q4W for up to 1 year did not improve DFS in the ITT population (mDFS 71.3 vs 68.8 months; HR 0.97; 1-sided p=0.39; n=466 vs 469) and was also negative in PD-L1 ≥50% tumors (mDFS 89.8 vs 78.5 months; HR 0.86; 1-sided p=0.22); the study stopped early for futility at 75% information. This contrasts with the current adjuvant IO “winners” after resection + platinum chemo—atezolizumab improved DFS in stage II–IIIA PD-L1–positive disease (PD-L1 ≥1% HR 0.66 in IMpower010), while pembrolizumab improved DFS vs placebo regardless of PD-L1 in KEYNOTE-091 (HR 0.76), highlighting that not all PD-1/PD-L1 strategies translate when moved into the purely postoperative setting.