As reported in the Journal of Clinical Oncology by Scherpereel et al, 5-year findings from the phase III CheckMate 743 trial showed continued overall survival benefit of first-line nivolumab plus ipilimumab vs chemotherapy in patients with unresectable pleural mesothelioma.
Study Details
In the trial, 605 patients were randomly assigned to receive nivolumab at 3 mg/kg every 2 weeks plus ipilimumab at 1 mg/kg every 6 weeks (n = 303) or cisplatin at 75 mg/m2 (or carboplatin AUC = 5) plus pemetrexed at 500 mg/m2 every 3 weeks (n = 302) for a maximum of six cycles. A total of 24% of the chemotherapy group subsequently received immunotherapy.
Key Findings
Median follow-up was 66.8 months. Overall survival at 5 years was 14% in the nivolumab plus ipilimumab group vs 6% in the chemotherapy group (hazard ratio [HR] = 0.74, 95% confidence interval [CI] = 0.62–0.88). Rates were 14% vs 8% among patients with epithelioid pleural mesothelioma (HR = 0.85, 95% CI = 0.69–1.03) and 12% vs 1% in those with nonepithelioid pleural mesothelioma (HR = 0.48, 95% CI = 0.33–0.68).
Among 242 biomarker-evaluable patients in the nivolumab plus ipilimumab group, those with high baseline monocytic myeloid–derived suppressor cell levels had significantly poorer overall survival (HR = 1.25, 95% CI = 1.09–1.43).
In analysis adjusting for patients in the chemotherapy group who subsequently received immunotherapy, nivolumab plus ipilimumab retained a significant overall survival benefit (HR = 0.64, 95% CI = 0.53–0.78).
The investigators concluded: “These results demonstrate long-term, durable clinical benefit with nivolumab plus ipilimumab versus chemotherapy, which continued to be preserved even after treatment-switching adjustment in the chemotherapy arm. Exploratory analyses suggested greater benefit with nivolumab plus ipilimumab in the low [monocytic myeloid–derived suppressor cell] subgroup. These results further support first-line nivolumab plus ipilimumab as standard of care for unresectable [pleural mesothelioma].”
Arnaud Scherpereel, MD, PhD, of University of Lille, CHU Lille, INSERM U1189 OncoThAI, ONCOLille, Lille, France, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by Bristol Myers Squibb. For full disclosures of the study authors, visit ascopubs.org.
