Clinical outcomes with perioperative nivolumab by nodal status in patients with stage III resectable NSCLC: phase 3...

Individuals with non-small-cell lung cancer (NSCLC) with metastases to the ipsilateral mediastinum or subcarinal lymph nodes (N2 disease) have poor long-term survival. This exploratory analysis from the randomized phase 3 CheckMate 77T study assessed clinical outcomes by nodal status in individuals with stage III NSCLC who received neoadjuvant nivolumab plus chemotherapy followed by surgery and adjuvant nivolumab (nivolumab) versus neoadjuvant chemotherapy followed by surgery and adjuvant placebo (placebo). Here we show that among patients with N2 disease, nivolumab versus placebo improved event-free survival (1-year rate, 70% versus 45%; hazard ratio, 0.46 (95% confidence interval, 0.30-0.70)) and pathological complete response rate (22.0% versus 5.6%); 77% versus 73% had definitive surgery, of whom 84% versus 74% received a simple lobectomy. Furthermore, nivolumab improved outcomes versus placebo in patients with multistation N2 NSCLC (1-year event-free survival rate: 71% versus 46%; hazard ratio, 0.43 (0.21-0.88); pathological complete response rate, 29.0% versus 2.7%). In the N2 subgroup with definitive surgery, 67% and 59% of patients had nodal downstaging after surgery (57% versus 44% downstaged to node-negative disease). Median EFS in randomized patients with stage III non-N2 NSCLC was not reached with nivolumab and 17.0 months with placebo (1-year EFS rate, 74% versus 62%; hazard ratio, 0.60 (0.33-1.08)). No new safety signals were identified. These findings support perioperative nivolumab plus neoadjuvant chemotherapy as an efficacious treatment for stage III N2 disease and suggest that N2 status may not predict poor prognosis in resectable NSCLC treated with perioperative immunotherapy. ClinicalTrials.gov identifier: NCT04025879 .