Checkmate 577

Background

CheckMate 577. Phase III, double-blind RCT enrolled 794 patients with stage II/III esophageal or GE junction cancer who had received neoadjuvant chemoradiotherapy and undergone R0 resection but had residual pathologic disease (ypN+ or ypT≥1), regardless of PD-L1 status, randomized 2:1.

Interventions and follow up

Arm A: Nivolumab 240 mg Q2W x 16 weeks, then 480 mg Q4W, up to 1 year total
Arm B: Placebo on the same schedule
Primary endpoint: Disease-free survival (DFS)
mFollow up: 24.4 mo

Results

mDFS (all patients): 22.4 mo vs 11.0 mo (arm A vs B); HR 0.69, 96.4%CI 0.56–0.86; P<.001
mDFS adenocarcinoma: 19.4 mo vs 11.1 mo; HR 0.75, 95%CI 0.59–0.96
mDFS squamous cell carcinoma: 29.7 mo vs 11.0 mo; HR 0.61, 95%CI 0.42–0.88

Adverse events

Overall: Grade≥3 treatment-related events 13% vs 6% (arm A vs B); any-grade events 71% vs 46%
Most common grade 3/4: Pneumonitis (<1%) and rash (<1%) in the nivolumab group, each in 1 placebo patient (<1%)

Conclusions

Adjuvant nivolumab significantly doubled disease-free survival versus placebo in patients with residual pathologic disease after neoadjuvant chemoradiotherapy and resection of esophageal/GE junction cancer.

Key Limitations

Overall survival data immature at primary report; benefit restricted to patients with residual disease after the CROSS chemoradiation paradigm (not applicable to perioperative-chemotherapy populations); placebo control rather than active comparator.

Clinical Context

Led to FDA (2021) and EMA approval of adjuvant nivolumab for resected esophageal/GE junction cancer with residual disease after neoadjuvant chemoradiation. Endorsed in ESMO/ASCO guidance and is now standard adjuvant therapy following the CROSS regimen.

References