In CheckMate 577 study conducted among patients with resected oesophageal or gastroesophageal junction cancer after neoadjuvant chemoradiotherapy, adjuvant therapy with nivolumab was associated with a significantly longer disease-free survival (DFS) than placebo. The safety profile of nivolumab was similar to that seen in other solid tumours. It is the second tumour type, after melanoma, for which nivolumab has provided a benefit in the adjuvant setting. Dr. Ronan J. Kelly of the Baylor University Medical Center in Dallas, TX, US and colleagues published the CheckMate 577 findings on 1 April 2021 in The New England Journal of Medicine.
The authors wrote in the study background that the incidence of oesophageal and gastroesophageal junction adenocarcinomas continues to increase in Western countries. The risk of recurrence after neoadjuvant chemoradiotherapy and surgery is high, especially among the 70-75% of patients who do not have a pathological complete response (pCR). The median overall survival among patients without a pCR is shorter than that among those with a pCR, and outcomes are even worse in patients with lymph node–positive disease.
The CheckMate 577 is a global, randomised, double-blind, placebo-controlled phase III study that evaluated adjuvant treatment with nivolumab after neoadjuvant chemoradiotherapy and surgery for oesophageal or gastroesophageal junction cancer. Patients with resected stage II or III oesophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy and had residual pathological disease were randomly assigned in a 2:1 ratio to receive adjuvant nivolumab or placebo. The primary endpoint was DFS.
The median follow-up was 24.4 months. Among the 532 patients who received nivolumab, the median DFS 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 [HR] for disease recurrence or death 0.69; 96.4% CI 0.56 to 0.86; p < 0.001).
Distant recurrence was less frequent in the nivolumab group than in the placebo group (29% and 39%, respectively), as was locoregional recurrence (in 12% and in 17%, respectively). A greater benefit of nivolumab than placebo was observed in patients with squamous cell cancer (HR 0.61) than in those with adenocarcinoma (HR 0.75). Benefit was also reported in patients with node-negative disease (HR 0.74) and node-positive disease (HR 0.67), across tumour stages, in patients with HER2-positive (HR 0.78) and HER2-negative disease (HR 0.69), in patients with tumours that were PD-L1–negative (HR 0.73) and PD-L1–positive (HR 0.75).
The median distant metastasis–free survival was 28.3 months (95% CI 21.3 to could not be estimated) in the nivolumab group and 17.6 months (95% CI 12.5 to 25.4) in the placebo group; thus, the risk of distant recurrence or death was 26% lower with nivolumab than with placebo (HR 0.74; 95% CI 0.60 to 0.92).
Grade 3 or 4 adverse events occurred in 13% of the patients in the nivolumab group and 6% in the placebo group. The study regimen was discontinued because of adverse events in 9% of the patients in the nivolumab group and 3% of those in the placebo group.
The study team reported that health-related quality of life was maintained during the treatment period.
Dr. David H. Ilson of the Memorial Sloan Kettering Cancer Center in New York, NY, US wrote in an accompanied article that patients with tumour in oesophagus had greater benefit (HR 0.61) than those with tumours of the gastroesophageal junction (HR 0.87). Furthermore, he commented that improvement in survival among patients with oesophageal cancer has been long awaited in those undergoing chemotherapy, radiation and surgerical treatment, so CheckMate 577 study results provide a new therapeutic option for these patients
The study was supported by Bristol Myers Squibb and Ono Pharmaceutical.