Abstract 3224: An indirect Meta-analysis of efficacy and safety of PD-1 inhibitors versus PD-L1 inhibitors as preoperative therapy in patients with solid tumors

Abstract Background: Programmed cell death 1 (PD-1) and ligand (PD-L1) immune checkpoint inhibitors (ICIs) in perioperative settings have improved clinical outcomes. However, it remains controversial which agent should be selected. We aim to compare the difference between anti-PD-1 and anti-PD-L1 efficacy and safety in neoadjuvant and/or adjuvant settings across randomized controlled trials. Methods: We systematically searched PubMed, Embase, Cochrane CENTRAL, and major oncology conferences up to May 20th, 2024. Clinical trials comparing anti-PD1 or anti-PD-L1 with standard care in perioperative settings were collected. These studies were further paired based on comparable characteristics and integrated as mirror groups. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guideline was followed for data extraction. Specifically, trial names, author, publication year, study design, blinding status, phase, pathologic characteristics, number of patients, settings of treatment, drugs, biomarker status, incidence of adverse events (AEs), pathological complete response (pCR), and major pathological response (MPR), and hazard ratios (HRs) with 95% confidence interval (CI) for event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) were extracted. A random or fixed model was used based on intertrial heterogeneity. Primary outcomes included pCR, MPR, EFS, DFS, OS, and AEs. Indirect comparisons between anti-PD-1 and anti-PD-L1 were conducted using Frequentist and Bayesian approaches. Result: Totally, 31 studies involving 14974 patients were included. Overall, anti-PD-1 demonstrated superior pCR (risk ratio (RR): 1·65, 95% CI: 1·18-2·29, P = 0·003) and MPR (RR: 1·43; 95% CI: 1·04-1·96, P = 0·026) when compared with anti-PD-L1, and was associated with improved DFS (HR = 0·82, 95% CI: 0·71-0·96, P = 0·0106). For PD-L1 expression, no differential benefits were observed between anti-PD-1 and anti-PD-L1. No significant discrepancies in overall safety profiles were noted, however, anti-PD-1 was linked to a higher incidence of 3-5 grade immune-related adverse event (irAE). Frequentist and Bayesian data were largely consistent. Conclusions: Anti-PD-1 therapy showed better clinical outcomes and higher incidence of serious irAEs to anti-PD-L1 in perioperative settings. These results may guide clinical decisions and trial designs, and further tumor-specific evaluations and mature trial data are needed. Citation Format: Peng Wu, Chaoqi Zhang, Dongyu Li, Xuanyu Gu, Junhan Zhou, Chuqi Lin, Nan Sun, Jie He. An indirect Meta-analysis of efficacy and safety of PD-1 inhibitors versus PD-L1 inhibitors as preoperative therapy in patients with solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3224.