Overview:
An analysis of disease-free survival (DFS) across pre-specified subgroups showed superior DFS with nivolumab compared with placebo regardless of histology and PD-L1 expression status.¹

Study population:
Patients with locally advanced oesophageal or gastro-oesophageal junction (GOJ) carcinoma who had received neoadjuvant platinum-based chemoradiotherapy followed by surgical resection (R0). Only patients who had residual pathological disease (≥ ypT1 or ≥ ypN1) were eligible for enrolment.¹

Study design:
CheckMate 577 is a global, randomized, double-blind phase 3 trial to evaluate adjuvant treatment with nivolumab in patients with locally advanced oesophageal or GOJ carcinoma who had received neoadjuvant platinum-based chemoradiotherapy followed by surgical resection (R0). Patients were randomized 2:1 to receive either intravenous nivolumab or placebo. Randomization was stratified according to tumor-cell PD-L1 expression (≥ 1% or < 1% [includes indeterminate/nonevaluable tumor-cell expression], indeterminate, or could not be evaluated), pathological lymph-node status (≥ ypN1 or ypN0), and histological type (squamous-cell carcinoma or adenocarcinoma).¹

Dosing:
Nivolumab 240 mg or placebo was administered as intravenous infusion over 30 minutes every two weeks for 16 weeks. Beginning at week 17, nivolumab 480 mg or placebo was administered over 30 minutes every four weeks for a maximum treatment duration of 12 months or until disease progression, unacceptable toxicity or withdrawal of consent occurred.¹

Study endpoints:
Primary endpoint was DFS and secondary endpoints were overall survival and survival at 1, 2 and 3 years. Exploratory end points included safety, distant metastasis-free survival (DMFS) and patient-reported outcomes (evaluated with the Functional Assessment of Cancer Therapy – Esophageal [FACT-E] scale and the three-level version of the European Quality of Life – 5 Dimensions questionnaire [EQ-5D-3L]).¹

Results:
A total of 794 patients were randomized in this study. The primary endpoint was met after a median follow-up of 24.4 months. Among the 532 patients who received adjuvant nivolumab, the median DFS at a median follow-up of 32.2 months was 22.4 months (95% CI, 16.9-33.6), as compared with 10.4 months (95% CI, 8.3-13.9) among the 262 patients who received placebo (hazard ratio (HR) 0.67; 95% CI, 0.55-0.81).¹

Safety:
Grade 3 or 4 treatment-related adverse events occurred in 14% of patients in the nivolumab arm and in 6% of patients in the placebo arm.¹

Reference:

1. Kelly RJ et al. Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer following neoadjuvant chemoradiotherapy: 14-month follow-up of CheckMate 577. KINGCA 09/2022, oral presentation.

Literature on request.