Perioperative Nivolumab Improves Survival in Resectable NSCLC

Although it has been proven that neoadjuvant chemoimmunotherapy improves survival compared with chemotherapy alone in non–small-cell lung cancer (NSCLC), whether perioperative immunotherapy would further improve outcomes is of interest. In this industry-sponsored phase 3 trial, 461 patients with resectable stage II and III NSCLC without known EGFR mutations or ALK translocations were randomized to receive neoadjuvant chemotherapy plus either nivolumab or placebo (every 3 weeks for 4 cycles), followed by surgery, followed by adjuvant nivolumab or placebo (every 4 weeks for 1 year).

In a prespecified interim analysis, event-free survival (the primary outcome) at 18 months was significantly higher in the nivolumab group than the placebo group (70.2% vs. 50.0%; hazard ratio, 0.58; P<0.001); median event-free survival was not reached versus 18.4 months, respectively. Pathological complete response occurred in 25.3% of patients in the nivolumab group compared with 4.7% in the placebo group.

In subgroup analyses, event-free survival was improved with perioperative nivolumab across categories of tumor PD-L1 expression, with greater magnitude of benefit in patients with higher PD-L1 expression.

Of note, chemotherapy was cisplatin based in 24% versus 18% of patients in the nivolumab and placebo groups, respectively, and was carboplatin based in 73% versus 78%. Grade 3 or 4 treatment-related adverse events occurred in 32.5% versus 25.2% of the nivolumab and placebo groups. Treatment-related adverse events led to treatment discontinuation in 19.3% versus 7.4% of patients, respectively.