Adjuvant Nivolumab Significantly Improves Disease-Free Survival in Esophageal Cancer

In a pivotal advancement for esophageal and gastroesophageal junction (GEJ) cancer treatment, the phase 3 CheckMate 577 study has demonstrated that adjuvant nivolumab significantly enhances disease-free survival (DFS) in patients post-chemoradiotherapy. This study's findings were prominently presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting by Dr. Ronan J. Kelly, MD, MBA, FASCO, chief of oncology at Baylor Scott & White Health in Dallas. The trial's results reinforce nivolumab's role as a standard of care for patients with residual pathologic disease following neoadjuvant therapy.

The CheckMate 577 trial involved a randomized, double-blind, placebo-controlled design, enrolling 794 patients with stage II or III esophageal or GEJ cancer who had undergone neoadjuvant chemoradiotherapy followed by surgical resection. Notably, patients exhibiting a pathologic complete response were excluded from the study, focusing instead on those with residual disease, indicative of aggressive tumor biology. Patients were assigned in a 2:1 ratio to receive either nivolumab or placebo for one year.

With a minimum follow-up of 5 years, the results indicated a median DFS of 21.8 months for the nivolumab group compared to 10.8 months for the placebo group (hazard ratio [HR] 0.76; 95% confidence interval [CI] 0.63-0.91). Furthermore, the overall survival (OS) in the nivolumab cohort was extended by 16.4 months, with median OS rates of 51.7 months versus 35.3 months in the placebo group, although this difference did not meet statistical significance (HR 0.85; p = 0.1064).

Dr. Kelly emphasized the significance of these findings, stating, "The data suggest a clinically meaningful improvement in OS with nivolumab, although statistical significance was not met. Looking at the OS subgroup analysis, however, did show that the majority of groups favored nivolumab."

The safety profile of nivolumab remained favorable, with no new safety signals identified over the extended follow-up period. A total of 49% of patients in the nivolumab group completed the treatment, compared to 44% in the placebo group, with disease progression being a more common reason for discontinuation in the placebo arm.

The study's subgroup analyses revealed that patients with esophageal cancer showed a significant benefit from nivolumab, while those with GEJ cancer exhibited limited efficacy. Notably, patients with a PD-L1 combined positive score (CPS) of 1 or greater experienced improved outcomes (HR 0.79), whereas those with a CPS of less than 1 had an HR of 1.4, indicating minimal benefit from immune checkpoint inhibition.

The implications of these findings extend to treatment paradigms for esophageal and GEJ cancers, with a clear shift towards perioperative therapies. As noted by Dr. Kelly, the increasing adoption of perioperative regimens reflects a growing preference for these treatment strategies. The CheckMate 577 study provides robust evidence supporting the use of adjuvant nivolumab as a standard of care, particularly in patients with esophageal squamous cell carcinoma.

As the field evolves, the findings from CheckMate 577 underscore the necessity for individualized treatment strategies and the potential for incorporating novel therapies into existing protocols. The FDA's recent approval of subcutaneous nivolumab for patients with resected esophageal and GEJ cancer further enhances therapeutic options in this challenging disease landscape. Looking ahead, the integration of ongoing research and emerging therapies will be crucial in optimizing outcomes for patients with esophageal and GEJ cancers.