Benefit of immune checkpoint inhibitors (ICI) for patients with advanced esophageal squamous cell carcinoma and low PD-L1 expression: A systematic review and meta-analysis.

Abstract

346 Background: Immunotherapy has improved survival for patients with advanced esophageal squamous cell carcinoma (aESCC) and currently is the standard of care for patients with a positive PD-L1 status (CPS ≥10; TPS ≥1%) in the first-line setting. For PD-L1 negative/low, treatment options are limited, and chemotherapy is usually the first choice and associated with adverse events that may impair quality of life. Immunotherapy trials harbor conflicting results in this subgroup of patients, therefore, we performed a systematic review and meta-analysis to evaluate the potential benefit of ICI as single treatment for patients with aESCC and a PD-L1 expression negative/low. Methods: Studies that enrolled patients with aESCC treated with ICI versus chemotherapy in first and second-line settings and provided separate outcomes for patients with PD-L1 negative/low were identified by searching the EMBASE, PubMed and Cochrane databases. The outcomes evaluated were Overall Survival (OS), Progression Free-Survival (PFS) and Treatment-Emergent Adverse Events (TEAE). We pooled hazard ratio (HR) for PFS and OS endpoints and odds ratio (OR) with 95% confidence intervals (CI) for TEAE. Statistical analyses were performed using Revman 5.4 and a random-effects model. I² analysis was used to assess heterogeneity. This meta-analysis was recorded on Prospero ID CRD42023411251. Results: We included 6 randomized clinical trials with a total of 674 individuals in the final analysis. Most studies (5/6) included previously treated patients. ICI monotherapy in aESCC patients and PD-L1 expression negative/low was associated with a better OS (HR 0.86; 95% CI 0.76-0.97; p = 0.02; I² = 0%) and worse PFS (HR 1.37; 95% CI 1.10-1.71; p = 0.005; I² = 0%). Regarding the safety profile, it showed higher grade 3-5 toxicity rates (OR 1.8; 95% CI 1.17-2.78; p = 0.007; I² = 85%) for chemotherapy. Conclusions: ICI is effective for patients with aESCC and low/negative PD-L1 expression with an improvement in OS and a favorable safety profile.