Neoadjuvant nivolumab plus chemotherapy significantly improved overall survival rates at 5 years compared with chemotherapy alone before surgery in patients with resectable non–small cell lung cancer (NSCLC), according to findings from the final analysis of the phase III CheckMate 816 trial. The results of the analysis were published in The New England Journal of Medicine and simultaneously presented at the 2025 ASCO Annual Meeting (Abstract LBA8000).
“Immunotherapy has helped many patients with stage IV lung cancer live longer with good quality of life. Until recently we have not had new treatments available that can increase the chances of cure after lung cancer surgery. The use of immunotherapy with chemotherapy before lung cancer surgery has now been shown to reduce the risk of cancer coming back and improve long-term survival. Cancer clinical trials are key to improving outcomes for patients with cancer and offer the potential for early access to the latest cutting-edge cancer treatments,” stated lead study author Patrick M. Forde, MB, BCh, PhD, Trinity St. James’s Cancer Institute, Trinity College Dublin, Ireland.
Study Methods and Results
The CheckMate 816 study explored the use of three cycles of neoadjuvant nivolumab plus platinum-based chemotherapy compared with chemotherapy alone, followed by surgery, in patients with stage IB to IIIA resectable NSCLC who did not have any known EGFR or ALK alterations.
Earlier results of the study, published in The New England Journal of Medicine, helped to establish this neoadjuvant regimen as a standard of care for eligible patients with resectable NSCLC and led to the U.S. Food and Drug Administration approval of this combination for this patient population.
A final analysis of the study was planned to assess overall survival at 5 years of follow-up.
At a median of 68 months follow-up, the overall survival was not reached in the neoadjuvant nivolumab plus chemotherapy arm compared with 73.7 months in the chemotherapy-alone arm (hazard ratio [HR] = 0.72; 95% confidence interval [CI] = 0.523–0.998; P = .0479). At 5 years, the overall survival rates were 65% with nivolumab and 55% without.
Among patients who achieved a pathological complete response to nivolumab and chemotherapy, the 5-year OS rate was 95% compared with 56% (HR = 0.11; 95% CI = 0.04–0.36).
Analysis showed that patients with positive PD-L1 expression (HR = 0.51; 95% CI = 0.31–0.84) and stage IIIA disease (HR = 0.70; 95% CI = 0.47–1.05) especially benefited from the addition of nivolumab.
Patients with presurgical circulating tumor DNA clearance had continued overall survival improvement in both treatment arms compared with those without.
Continued improvements were also seen in event-free survival with a median event-free survival of 59.6 months with nivolumab and chemotherapy compared with 21.1 months with chemotherapy alone (HR = 0.68; 95% CI = 0.51–0.91) and 5-year rates were 49% vs 34%, respectively.
“CheckMate 816 is the only neoadjuvant-only immunotherapy phase III trial to demonstrate a statistically and clinically significant overall survival benefit at 5 years for a resectable solid tumor,” the study authors concluded in their abstract. “The findings show long-term survival benefit from a short course of neoadjuvant nivolumab plus chemotherapy and affirm a paradigm shift in the treatment of resectable NSCLC without actionable genomic alterations.”
Next Steps
Dr. Forde is continuing to explore further improvements in survival outcomes for patients with NSCLC undergoing surgery. Results from part of the phase II NeoCOAST-2 trial that he is co-leading were recently published in Nature Medicine showing the potential for other neoadjuvant regimens in patients with resectable NSCLC. Rates of pathological complete response were higher with the combination of the TROP-2 antibody-drug conjugate datopotamab deruxtecan and chemotherapy with neoadjuvant durvalumab, warranting further investigation.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
