Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer

N Engl J Med. 2021 Apr 1;384(13):1191-1203. doi: 10.1056/NEJMoa2032125.


Background: No adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageal junction cancer.

Methods: We conducted CheckMate 577, a global, randomized, double-blind, placebo-controlled phase 3 trial to evaluate a checkpoint inhibitor as adjuvant therapy in patients with esophageal or gastroesophageal junction cancer. Adults with resected (R0) stage II or III esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy and had residual pathological disease were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by nivolumab at a dose of 480 mg every 4 weeks) or matching placebo. The maximum duration of the trial intervention period was 1 year. The primary end point was disease-free survival.

Results: The median follow-up was 24.4 months. Among the 532 patients who received nivolumab, the median disease-free survival was 22.4 months (95% confidence interval [CI], 16.6 to 34.0), as compared with 11.0 months (95% CI, 8.3 to 14.3) among the 262 patients who received placebo (hazard ratio for disease recurrence or death, 0.69; 96.4% CI, 0.56 to 0.86; P<0.001). Disease-free survival favored nivolumab across multiple prespecified subgroups. Grade 3 or 4 adverse events that were considered by the investigators to be related to the active drug or placebo occurred in 71 of 532 patients (13%) in the nivolumab group and 15 of 260 patients (6%) in the placebo group. The trial regimen was discontinued because of adverse events related to the active drug or placebo in 9% of the patients in the nivolumab group and 3% of those in the placebo group.

Conclusions: Among patients with resected esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy, disease-free survival was significantly longer among those who received nivolumab adjuvant therapy than among those who received placebo. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 577 number, NCT02743494.).

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / surgery
  • Adenocarcinoma / therapy*
  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / metabolism
  • Carcinoma, Squamous Cell / therapy*
  • Chemoradiotherapy, Adjuvant
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Double-Blind Method
  • Esophageal Neoplasms / immunology
  • Esophageal Neoplasms / surgery
  • Esophageal Neoplasms / therapy*
  • Esophagogastric Junction*
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Intention to Treat Analysis
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Nivolumab / adverse effects
  • Nivolumab / therapeutic use*
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / surgery
  • Stomach Neoplasms / therapy


  • B7-H1 Antigen
  • CD274 protein, human
  • Immune Checkpoint Inhibitors
  • Nivolumab

Associated data