Adjuvant Nivolumab Shows Sustained Benefit in Resected Esophageal Cancer

New data presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting confirms that adjuvant nivolumab (Opdivo) continues to provide a clinically meaningful advancement in disease-free survival (DFS) for patients with resected esophageal or gastroesophageal junction (GEJ) cancer who have residual pathologic disease following neoadjuvant chemoradiotherapy. The five-year follow-up data from the phase 3 CheckMate 577 trial solidifies adjuvant nivolumab as a standard of care for this patient population, according to findings presented by Dr. Ronan Kelly.

the CheckMate 577 study initially demonstrated a important improvement in DFS with adjuvant nivolumab compared to placebo. With a minimum follow-up of five years, the median DFS was 21.8 months with nivolumab compared to 10.8 months with placebo (HR, 0.76). While overall survival (OS) was prolonged by 16.4 months with nivolumab versus placebo, this difference did not reach statistical importance (HR, 0.85). The safety profile of nivolumab remained consistent with previous reports, showing it was well-tolerated over the extended follow-up period.

Did You Know? Immunotherapy drugs like nivolumab harness the body’s own immune system to fight cancer cells,offering a targeted approach with potentially fewer side effects than conventional chemotherapy.

Key Findings from CheckMate 577

The CheckMate 577 trial, a phase 3 study, evaluated the efficacy and safety of adjuvant nivolumab in patients with resected esophageal or GEJ cancer who had residual pathologic disease after neoadjuvant chemoradiotherapy. The study’s findings, presented at the 2025 ASCO Annual Meeting, provide critical insights into the long-term benefits of this treatment approach.

Disease-Free Survival (DFS)

The updated DFS data showed a sustained benefit with adjuvant nivolumab. The median DFS increased from 10.8 months with placebo to 21.8 months with nivolumab, representing a clinically meaningful improvement. The hazard ratio (HR) of 0.76 indicates a 24% reduction in the risk of disease recurrence or death with nivolumab.

Overall Survival (OS)

While the median OS was prolonged by 16.4 months with nivolumab compared to placebo, the difference did not reach statistical significance. The median OS was 51.7 months with nivolumab and 35.3 months with placebo (HR,0.85).however,the 5-year OS rate was higher in the nivolumab arm (46%) compared to the placebo arm (41%),suggesting a clinically relevant benefit.

Safety Profile

Nivolumab continued to demonstrate a favorable toxicity profile with no new safety signals observed over the extended follow-up. The incidence of treatment-related adverse effects remained consistent with previously reported results, reinforcing the tolerability of this treatment.

Subgroup Analyses and Treatment Paradigms

Subgroup analyses from CheckMate 577 revealed critically important insights into the role of PD-L1 expression and histology in response to adjuvant nivolumab.These analyses also shed light on evolving treatment paradigms for esophageal and GEJ cancers.

PD-L1 Expression and histology

Patients with immunologically “hot” tumors, defined as a PD-L1 combined positive score (CPS) of 1 or greater, showed improved outcomes with adjuvant nivolumab. In contrast, those with “cold” tumors (CPS less than 1) had limited benefit.Regarding histology, both adenocarcinoma and squamous cell carcinoma responded to nivolumab, with a slightly better hazard ratio observed in squamous cell carcinoma.

Evolving Treatment Paradigms

For patients with esophageal squamous cell carcinoma, the treatment approach used in the CheckMate 577 study-neoadjuvant chemoradiation followed by surgery and one year of adjuvant nivolumab-remains the standard of care.However, for GEJ and gastric cancers, perioperative regimens are gaining favor. Recent data suggests that durvalumab in combination with chemotherapy may become a new standard of care for these cancers National Cancer Institute.

Pro Tip: Individualized treatment decisions are crucial in esophageal and GEJ cancers. Factors such as patient fitness,tumor histology,and PD-L1 expression should be considered when selecting the most appropriate treatment approach.

Impact of Subsequent Systemic Therapy

The effect of subsequent systemic therapy on outcomes was evaluated, revealing that approximately 60% of patients in the placebo arm received subsequent treatment compared to 46% in the nivolumab arm. To account for the confounding effects of subsequent treatment,a two-stage adjustment method was used. After adjusting for the impact of subsequent treatments, the median OS was 38.6 months with nivolumab versus 20.2 months with placebo, with an adjusted HR of 0.73.

The results of the CheckMate 577 trial and subsequent analyses support the use of adjuvant nivolumab as a standard of care in patients with resected esophageal or GEJ cancer who have residual pathologic disease following neoadjuvant chemoradiotherapy. The sustained DFS benefit and encouraging OS data reinforce the role of this treatment in improving outcomes for this patient population.

The FDA has approved subcutaneous nivolumab for patients with resected esophageal and GEJ cancer with residual disease after trimodality therapy, offering an alternative route for administration FDA.

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Disclaimer: This article provides information about medical research and treatment options. It is not intended to be a substitute for professional medical advice. Always consult with a qualified healthcare provider for any questions you may have regarding your health or treatment.

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