As reported in the Journal of Clinical Oncology by Awad et al, exploratory analysis of the comparison of neoadjuvant nivolumab/ipilimumab vs chemotherapy in the phase III CheckMate 816 trial found that nivolumab/ipilimumab was associated with numerically better event-free survival in patients with resectable non–small cell lung cancer (NSCLC).
Study Details
In the international trial, patients with stage IB to IIIA disease were randomly assigned to receive neoadjuvant nivolumab plus platinum-doublet chemotherapy, nivolumab/ipilimumab, or platinum-doublet chemotherapy. The previously reported primary analysis of the trial showed superiority of nivolumab plus chemotherapy over chemotherapy alone in event-free survival and pathologic complete response rate. The current analysis features the comparison of the nivolumab/ipilimumab group (n = 113) vs the chemotherapy group (n = 108). Nivolumab was given at 3 mg/kg every 2 weeks for three cycles, and ipilimumab was given at 1 mg/kg for one dose in cycle 1 alone; chemotherapy was given on day 1 or on days 1 and 8 of each 3-week cycle.
Key Findings
Median follow-up was 49.2 months (range = 37.1–65.2 months). Median event-free survival was 54.8 months (95% confidence interval [CI] = 24.4 months to not reached) in the nivolumab/ipilimumab group vs 20.9 months (95% CI = 14.2 months to not reached) in the chemotherapy group (hazard ratio [HR] = 0.77, 95% CI = 0.51–1.15), with a 3-year rate of 56% vs 44%. The event-free survival curve crossed at approximately 11 months, with later benefit favoring nivolumab/ipilimumab.
Subsequent anticancer therapy of any kind was received by 32% vs 49% of patients. Overall survival data were not yet mature. Overall survival at 3 years was 73% vs 61% (HR = 0.73, 95% CI = 0.47–1.14). Pathologic complete response was observed in 20.4% vs 4.6% of patients (odds ratio = 5.14, 95% CI = 1.91–13.80).
Grade 3 or 4 treatment-related adverse events were reported in 14% of the nivolumab/ipilimumab group vs 36% of the chemotherapy group. Treatment-related serious events occurred in 9% vs 14% of patients, and treatment-related adverse events led to discontinuation of treatment in 5% vs 7%. One treatment-related death was observed, in a patient in the chemotherapy group.
The investigators concluded: “Neoadjuvant nivolumab plus ipilimumab showed potential long-term clinical benefit [vs] chemotherapy, despite early crossing of [event-free survival] curves in the preoperative phase[,] and a lower rate of high-grade toxicity.
Mark M. Awad, MD, PhD, of Dana-Farber Cancer Institute, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Bristol Myers Squibb and Ono Pharmaceutical Company, Ltd. For full disclosures of all study authors, visit the Journal of Clinical Oncology.
