Neoadjuvant Nivolumab Plus Ipilimumab Shows Promise in Resectable NSCLC with Lower Toxicity
A recent exploratory analysis from the phase 3 CheckMate 816 trial evaluated the efficacy and safety of neoadjuvant nivolumab plus ipilimumab compared with chemotherapy in resectable stage IB-IIIA non-small cell lung cancer (NSCLC).
The trial enrolled 221 adults with NSCLC who were randomized to receive nivolumab (3 mg/kg every 2 weeks for three cycles) plus ipilimumab (1 mg/kg once) or standard chemotherapy. Surgery followed within 6 weeks, and optional adjuvant therapy was provided at the investigator’s discretion.
After a median follow-up of 49.2 months, nivolumab plus ipilimumab showed a median event-free survival (EFS) of 54.8 months versus 20.9 months with chemotherapy (HR = 0.77). Three-year EFS and overall survival rates were 56% vs. 44% and 73% vs. 61%, respectively. Pathologic complete response (pCR) rates were significantly higher with nivolumab plus ipilimumab (20.4% vs. 4.6%), and recurrence rates were lower (23% vs. 44%). Notably, R0 resection was achieved in 80% of nivolumab plus ipilimumab patients compared with 71% with chemotherapy. Grade 3-4 treatment-related adverse events were less frequent with nivolumab plus ipilimumab (14% vs. 36%).
Study limitations include the exploratory nature of the analyses, small sample sizes for biomarker evaluations, and a higher rate of early progression events in the nivolumab plus ipilimumab group, which precluded surgery for some patients.
“This report highlights the complexities of neoadjuvant immune checkpoint blockade with not only higher rates of early tumor progression occurring with neoadjuvant nivolumab plus ipilimumab but also high pCR rates, low-grade 3-4 treatment-related adverse events, and evidence of long-term clinical benefit,” the study authors wrote.
Reference
Awad MM, Forde PM, Girard N, et al. Neoadjuvant nivolumab plus ipilimumab versus chemotherapy in resectable lung cancer. J Clin Oncol. Published online January 8, 2025. doi:10.1200/JCO-24-02239