Safety and efficacy of PD-1/PD-L1 inhibitor plus chemotherapy versus chemotherapy alone in esophageal squamous cell carcinoma: A systematic review and meta-analysis.

Abstract

e16024 Background: Patients with advanced esophageal squamous cell carcinoma (ESCC) continue to have poor outcomes with chemotherapy alone. The addition of PD-L1 inhibitors to first-line chemotherapy has shown encouraging results in individual trials, but the overall magnitude and consistency of benefit across key clinical endpoints have not been fully clarified. To better understand the effects of PD-L1 inhibitors used in combination with chemotherapy, we performed a systematic review and meta-analysis to compare the efficacy and safety of PD-L1-based combination therapies to chemotherapy alone in patients with advanced or metastatic ESCC. Methods: A systematic search of PubMed, Embase, and Scopus identified randomized controlled trials comparing PD-L1 inhibitor plus chemotherapy versus chemotherapy alone in patients with advanced or metastatic ESCC. Three eligible studies met inclusion criteria. We calculated pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS); and pooled risk ratios (RRs) for objective response rate (ORR) and Grade 3-5 treatment-related adverse events (TRAEs) using random effects models. We quantified the heterogeneity among studies using the I² test. Results: Across three randomized trials, the addition of a PD-L1 inhibitor to chemotherapy resulted in a statistically significant and highly consistent survival advantage. OS was longer with combination therapy (HR 0.67, 95% CI 0.60–0.76; p < 0.00001), representing a 33% reduction in the risk of death, with no heterogeneity across studies (I² = 0%). Similarly, PFS was prolonged with combination therapy (HR 0.61, 95% CI 0.55–0.68; p < 0.00001; I² = 0%), corresponding to a 39% reduction in the risk of disease progression or death. Tumor responses occurred at higher frequencies in patients who received PD-L1 inhibitor-based therapy than in patients who received chemotherapy alone (RR = 1.49, 95% CI = 1.35-1.63; p < .00001; I² = 0%). The increased efficacy observed with combination therapy was not accompanied by an increase in severe toxicities. The rates of Grade 3-5 TRAEs were similar between the two groups (RR = 1.06, 95% CI = 0.99-1.13; p = 0.09; I² = 0%). Conclusions: Based on evidence from three randomized trials, the addition of PD-L1 inhibitors to standard chemotherapy improves both survival and response rates in patients with advanced ESCC without an increase in severe treatment related adverse events. Therefore, PD-L1-based combination therapies represent a promising new therapeutic option for patients with advanced ESCC.