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TOPLINE:

Adding nivolumab to neoadjuvant chemotherapy significantly improved 5-year overall survival among patients with resectable non-small cell lung cancer (NSCLC), according to findings from a phase 3 trial presented at the recent American Society of Clinical Oncology (ASCO) 2025 annual meeting. The survival benefit was more pronounced in patients who achieved a pathologic complete response or a presurgery clearance of circulating tumor DNA (ctDNA).

METHODOLOGY:

• The phase 3 CheckMate 816 trial has shown that compared with neoadjuvant chemotherapy alone, nivolumab plus chemotherapy improvespathologic complete response rates and event-free survival in patients with stage IB-IIIA resectable NSCLC. Based on these findings, this regimen was approved for this patient population in the US, EU, and other places.
• Researchers are now reporting the final, prespecified analysis of overall survival. In the trial, 358 patients with stage IB-IIIA resectable NSCLC were randomly assigned to receive either nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone every 3 weeks for three cycles.
• Surgery was performed within 6 weeks of completing neoadjuvant treatment. Postoperative adjuvant chemotherapy, radiotherapy, or both were permitted.
• Primary endpoints were event-free survival and pathologic complete response. Overall survival was the key secondary endpoint.
• The median follow-up duration was 68.4 months.

TAKEAWAY:

• The 5-year overall survival rate was 65.4% with nivolumab plus chemotherapy vs 55.0% with chemotherapy alone. Nivolumab plus chemotherapy reduced the risk for death by 28% (hazard ratio [HR], 0.72; P = .048).
• Among patients who received the combination therapy, the 5-year overall survival rate was 95.3% for those who achieved a pathological complete response vs 55.7% for those who did not. Overall, 24% of patients in the nivolumab group achieved a pathological complete response vs only 2.2% in the chemotherapy group.
• ctDNA clearance before surgery was a strong prognostic indicator, regardless of treatment. At 5 years, overall survival was 75.0% among patients with ctDNA clearance vs 52.6% in those without (HR for death, 0.38 in the nivolumab group and 0.39 in the chemotherapy-only group).
• The combination therapy was associated with consistent survival benefits across disease stage and PDL-1 expression levels. The 5-year lung cancer-specific survival rate was 74.9% with nivolumab plus chemotherapy vs 65.1% with chemotherapy alone (HR, 0.65). No new safety concerns emerged, and there were no new deaths related to a trial treatment.

IN PRACTICE:

“In this trial, we found that the use of neoadjuvant nivolumab plus chemotherapy resulted in significantly longer overall survival than chemotherapy alone, along with long-term benefit regarding event-free survival,” the authors wrote. “These findings support the hypothesis that neoadjuvant chemoimmunotherapy can have a profound impact on the course of a patient’s life when paired with the curative potential of surgical resection.”

SOURCE:

This study, led by Patrick M. Forde, MB, BCh, PhD, Trinity St. James’s Cancer Institute, Trinity College Dublin, Dublin, Ireland, was published online in The New England Journal of Medicine and presented at ASCO.

LIMITATIONS:

Although the overall survival with nivolumab plus chemotherapy achieved statistical significance, the margin was narrow. Additionally, several subgroups in the exploratory analyses were too small for adequate statistical comparison, requiring cautious interpretation of these results. Black patients were underrepresented, which may have affected the generalizability of the findings.

DISCLOSURES:

This study was funded by Bristol Myers Squibb. Five authors declared being employees of Bristol Myers Squibb, with some holding stock or stock options with the company. Several authors declared working as consultants or having other ties with various sources including Bristol Myers Squibb.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.