FOLFOX plus nivolumab combination therapy for cisplatin-unfit patients with untreated advanced esophageal squamous cell carcinoma

Combination chemotherapy with cisplatin and fluorouracil plus an immune checkpoint inhibitor (ICI) is a standard first-line treatment for advanced esophageal squamous cell carcinoma (ESCC). However, cisplatin is unsuitable for patients with renal or cardiac dysfunction and older patients because of nephrotoxicity and the need for hydration. Oxaliplatin-based regimens (e.g., FOLFOX) have demonstrated clinically meaningful efficacy and are well tolerated in cisplatin-unfit patients with untreated advanced ESCC. This study investigated the effectiveness and safety of FOLFOX combined with an ICI in these patients.

Cisplatin-unfit patients with untreated advanced ESCC who received FOLFOX plus nivolumab at our institution between January 2024 and July 2025 were retrospectively identified. Progression-free survival, overall survival, and the response rate were evaluated as efficacy endpoints and adverse events as safety endpoints.

Seventeen patients with a median age of 75 years (range, 62–82) were included. ECOG performance status was 0 in 3 cases (17.6%), 1 in 11 (64.7%), and 2 in 3 (17.6%). The main reasons for cisplatin ineligibility were older age (88.2%) and poor condition (58.8%). The response rate was 57.1% in patients with measurable lesions during a median follow-up of 9.9 months. Median progression-free survival was 6.5 months (95% confidence interval 3.6–not reached [NR]) and median overall survival was 15.6 months (4.5–NR). Common adverse events were neutropenia (41.2%) and leukopenia (35.3%). No treatment-related deaths occurred.

FOLFOX plus nivolumab might have effectiveness and safety comparable with that of cisplatin and fluorouracil plus nivolumab in cisplatin-unfit patients with untreated advanced ESCC.