Purpose: Blockade of the PD-L1/PD-1 pathway combined with chemotherapy has demonstrated significant survival benefits as first‑line therapy for esophageal squamous cell carcinoma (ESCC). However, comprehensive benefit-risk comparisons among approved agents remain limited. This study conducted an indirect comparison of serplulimab versus other anti-PD-1/PD-L1 antibodies plus chemotherapy in treatment-naïve ESCC patients. Patients and Methods: A systematic review with matching-adjusted indirect comparisons (MAICs) was conducted using individual patient data (IPD) from ASTRUM-007 and aggregate data (AgD) from seven comparator trials, including CheckMate 648, ESCORT-1st, GEMSTONE-304, JUPITER-06, KEYNOTE-590, ORIENT-15, and RATIONALE-306. IPD were reweighted to match key baseline characteristics. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were estimated using the Bucher method. Subgroup analyses were further explored using Bayesian network meta-analysis. Results: Eight Phase 3 randomized controlled trials comprising 4,702 patients were included. After adjusting for baseline imbalances, serplulimab demonstrated comparable efficacy to other PD-1/PD-L1 inhibitors. The pooled adjusted OS HR was 0.98 (95% CI, 0.87– 1.11), with numerically favorable OS versus nivolumab (HR, 0.76; 95% CI 0.47– 1.24) and comparable OS versus pembrolizumab (HR, 0.93; 95% CI, 0.71– 1.22) and camrelizumab (HR, 0.93; 95% CI, 0.70– 1.24). The pooled adjusted PFS HR was 0.91 (95% CI, 0.81– 1.02), significantly favoring serplulimab over nivolumab (HR, 0.56; 95% CI, 0.33– 0.96), with favorable trends versus pembrolizumab (HR, 0.83; 95% CI, 0.63– 1.10) and sugemalimab (HR, 0.86; 95% CI, 0.63– 1.16). Subgroup analyses suggested greater relative benefit in women and patients with locally advanced disease. Grade 3– 5 treatment-related adverse events occurred in 52.9% of serplulimab-treated patients, comparable to other PD-1/PD-L1 inhibitors (range, 47.4%-71.9%). Conclusion: This indirect comparison provides comparative benefit-risk evidence to inform first‑line treatment selection for locally advanced or metastatic ESCC. Serplulimab plus chemotherapy demonstrated a clinically meaningful PFS benefit, comparable OS after matching, and a manageable safety profile consistent with the PD-1/PD-L1 inhibitor class. Keywords: matching-adjusted indirect comparison, immune checkpoint inhibitor, esophageal neoplasms, benefit-risk assessment, first-line therapy
Zhu et al. (Sun,) studied this question.