Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer

Abstract

BACKGROUNDNo 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. METHODSWe 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. RESULTSThe 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. CONCLUSIONSAmong 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 ClinicalTrials.gov number, NCT02743494.

Efficacy and safety of neoadjuvant chemotherapy and immunotherapy in locally resectable advanced esophageal squamous cell carcinoma

“…For locally advanced stages, the five-year survival period is frustrating, ranging from 17-23%, which may be slightly higher in patients with resectable diseases (2)(3)(4)(5), and the current National Comprehensive Cancer Network (NCCN) guidelines recommend neoadjuvant therapy (6). Now, immunotherapy as a new treatment is effective when used alone in resectable esophageal cancer (7). More and more evidence of neoadjuvant immunotherapy suggests that it can improve the prognosis of unresectable tumors, and immunotherapy drugs have become diverse, such as "Camrelizumab, Pembrolizumab or Sintilimab," etc.…”

New Trends in Esophageal Cancer Management

“…Recent randomized trials have demonstrated the value of anti-PD1 and anti-PDL1 in the treatment of advanced or metastatic EC [ 32 , 33 ] and as adjuvant treatment after R0 resection [ 34 ].…”

Understanding the immuno-biology of oesophageal adenocarcinoma: Towards improved therapeutic approaches

“…Although this study only included 10 tumour samples, the results are in stark contrast to Western tumour findings and lay the groundwork for further comparative studies between Asian and non-Asian patients. Outcome differences between Asian and non-Asian patients have been conflicting across immunotherapy trials, with CheckMate 649 reporting an overall survival (OS) benefit for Asian patients, whereas no difference was seen for DFS in CheckMate 577 [10,27]. No studies to date have compared the tumour microenvironment (TME) of OAC between Asian and non-Asian patients, and integrative studies comparing the TME and underlying genomic features may inform geographically relevant biomarkers and therapeutic strategies.…”

“…Most oesophageal cancer (OC) and gastro-oesophageal cancer (GOC) immunotherapy trials have focussed on second-or third-line treatment of advanced/metastatic disease, and although encouraging, results have only shown modest survival increases compared with CT (Table 1). Recently however, results from the CheckMate-577 trial, where patients treated with adjuvant Nivolumab following CRT and surgical resection, showed significantly increased disease-free survival (DFS) compared to placebo [10] (Table 1).…”