Tolerability of Adjuvant Nivolumab in Esophageal or Gastroesophageal Junction Cancer: A Real-World Study.

Adjuvant nivolumab is approved for esophageal or gastroesophageal junction cancer after neoadjuvant chemoradiotherapy and resection. In the CheckMate-577 trial, Grade 3-5 nivolumab-related adverse events (AEs) occurred in 5% of patients, with early discontinuation due to toxicity in 9%. However, real-world data on immunotherapy-related adverse events (irAEs) are limited. This study assessed the cumulative incidence of irAEs in a real-world setting. In this retrospective cohort study, all patients receiving ≥ 1 cycle of adjuvant nivolumab at three Dutch gastroesophageal cancer centers were included. Clinical data were extracted from electronic records. The primary outcome was the cumulative incidence of Grade 3-5 irAEs. Secondary outcomes included predictors, timing, and clinical outcomes of Grade 3-5 irAEs, and cumulative incidence of Grade 2 irAEs. Among 142 patients with median follow-up 27.9 months, Grade 3-5 irAEs occurred in 15%. Hepatitis (3%), pneumonitis (2%), and myocarditis (2%) were most common. Two fatal irAEs occurred (1%). Median time to first Grade 3-5 irAE was 2.0 months (IQR 0.7-6.4). Grade 3-5 irAEs led to hospitalization in 9%, required systemic corticosteroids in 11%, and resulted in clinical sequelae in 8%. No predictors for Grade 3-5 irAEs were identified. Early discontinuation due to any irAE occurred in 24%. In conclusion, severe irAEs (Grade 3-5) occurred more frequently than in CheckMate-577 and often required hospitalization and immunosuppression, with sequelae in a significant proportion. Discontinuation due to irAEs was higher than in CheckMate-577 (24% vs. 9%). Careful risk-benefit assessment and active monitoring during adjuvant nivolumab therapy are warranted.