Another criticism of the study design might be that tumor location was not a stratification criterion at randomization. As expected, patients with esophageal squamous cell cancer had a much larger disease-free survival benefit from adjuvant nivolumab (hazard ratio = 0.61, 95% confidence interval = 0.42–0.88) compared with patients who had esophageal adenocarcinoma (HR = 0.78, 95% CI = 0.59–0.96). This approach must be questioned, given that these two histologic subtypes have a totally different genomic background and tumor biology, according to The Cancer Genome Atlas investigators, and respond differently to neoadjuvant radiochemotherapy and immune checkpoint inhibitors. This important question is currently being investigated in the European Organisation of Research and Treatment of Cancer VESTIGE study.ĭifferent Histologies, Different Responsesīoth patients with esophageal squamous cell cancer and esophageal adenocarcinoma were enrolled in CheckMate 577. It is currently unknown whether adjuvant immunotherapy improves outcomes following neoadjuvant chemotherapy and surgery in patients with esophagogastric junction adenocarcinoma (types I–III) or gastric cancer. Results from randomized controlled trials comparing both approaches -(ESOPEC and Neo-AEGIS) are awaited.

Following European Society for Medical Oncology guidelines, the latter approach is particularly common in Europe but also in parts of North America, Latin America, the United Kingdom, and Australia-New Zealand. Although trimodality treatment is a widely accepted standard of care for patients with esophageal squamous cell cancer, at least in the Western world, esophageal adenocarcinoma is treated either with neoadjuvant radiochemotherapy or perioperative chemotherapy. However, many centers worldwide have adopted different treatment strategies for esophageal squamous cell cancer and esophageal adenocarcinoma. Histologic Subtype May Guide Treatment SelectionĬenters that recommend neoadjuvant radiochemotherapy for both histologic subtypes of locally advanced esophageal cancer may now feel prompted to use nivolumab for all patients with residual tumor in the resection specimen. The short disease-free survival in the control arm underpins the selection of a poor prognostic group of patients for this trial. Disease-free survival doubled from 11 months to 22 months in nivolumab-treated patients, suggesting that longer follow-up may also show a difference in overall survival. In CheckMate 577, 1 year of adjuvant nivolumab dramatically improved outcomes for patients with high-risk esophageal cancer following trimodality therapy. FLORIAN LORDICK, MD, PhD Tweet this quote

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