Nivolumab Exhibits Enhanced DFS Outcomes in Resected Gastric Cancers

Ronan J. Kelly, MD, MBA, director of Oncology at the Charles A. Sammons Cancer Center, and W.W. Caruth Jr., Endowed Chair of Immunology at Baylor University Medical Center in Dallas, Texas, spoke with CancerNetwork® about efficacy findings from a 5-year follow-up analysis of the phase 3 CheckMate 577 study (NCT02743494) evaluating nivolumab (Opdivo) in patients with resected esophageal or gastroesophageal junction (GEJ) cancer previously treated with chemoradiation. He presented these data in an oral session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

He began by outlining findings related to the primary end point of disease-free survival (DFS), expressing that after 5 years of follow-up, the median DFS favored the investigational therapy with a hazard ratio (HR) of 0.76. Additionally, he expressed that the separation of the Kaplan-Meier curves between the investigational and control regimens continued through 5 years of follow-up.

Furthermore, he expressed that distant metastasis-free survival, an exploratory end point, and overall survival (OS), a secondary end point, both numerically favored nivolumab, with respective HRs of 0.75 and 0.85. He concluded by explaining that although a clinically meaningful improvement was observed with OS, outcomes fell short of attaining statistical significance.

Transcript

The primary end point of the [phase 3 CheckMate 577] study was disease-free survival. We’re now able to show 5 years of [follow-up]. It continued to show a clinically meaningful improvement for nivolumab vs placebo. With this longer follow up, the median disease-free survival was 10.8 months in the placebo arm and 21.8 months in the nivolumab arm with the hazard ratio of 0.76 [while] maintaining that doubling of disease-free survival, which we’ve shown five years ago…the shape of the curves show that they separate at approximately 3 to 4 months. And if you look at the 5-year disease-free survival rate, it was 29% in the placebo group vs 37% in the nivolumab arm.

Distant metastasis-free survival was an exploratory endpoint on this study. Here, again, we showed that nivolumab prevents distant metastasis. If we look at the [median] distant metastasis-free survival, it was 14.6 months with placebo vs 27.3 months with nivolumab, [with a] hazard ratio of 0.75. Again, the curves separate at that 4-month mark and remain separated. If you look at the 60-month or 5-year distant metastasis-free survival rates, it was 38% with nivolumab vs 29% with placebo.

Overall survival was a secondary endpoint, and here, for the first time, we showed the final results of overall survival after a minimum follow-up of five years, which was as per study design. What we showed was the median overall survival was longer with nivolumab vs placebo, 16.4 months longer, with a median OS of 35.3 months [with] placebo vs 51.7 months with nivolumab. Also, the 5-year overall survival rates were higher at 41% with placebo vs 46% with nivolumab, suggesting a clinically meaningful improvement in overall survival, although statistical significance was not met with a hazard ratio of 0.85.

Reference

Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer (EC/GEJC) following neoadjuvant chemoradiotherapy (CRT): first results of overall survival (OS) from CheckMate 577. J Clin Oncol. 2025;43(suppl 16):4000. doi:10.1200/JCO.2025.43.16_suppl.4000