Immunotherapy with anti-PD-1 or PD-L1 in advanced ovarian cancer: A meta-analysis of randomized trials

Background Ovarian cancer remains the gynecological malignancy with the highest mortality rate. Despite advances in treatment, the median overall survival remains suboptimal. Although there is strong biological rationale for the use of immune checkpoint inhibitors (ICIs), their clinical efficacy in ovarian cancer remains uncertain. This study aimed to evaluate the effectiveness of anti–PD-1/PD-L1 agents in advanced ovarian cancer by reviewing randomized trials. Methods We performed a systematic review and meta -analysis of randomized controlled trials (RCTs). Data sources included PubMed, EMBASE, the Cochrane Library, and major conference abstracts, with searches conducted up to July 1, 2025. Eligible studies included RCTs comparing anti–PD-1/PD-L1 agents (with or without chemotherapy) to standard treatments in patients with advanced ovarian cancer (first-line, platinum-sensitive, or platinum-resistant). Trials with fewer than 50 patients or non-randomized designs were excluded. Two authors independently extracted summary-level data. The primary outcome measure was progression-free survival (PFS) in the intention-to-treat population. A random-effects model was used to estimate pooled hazard ratios (HRs). Risk of bias was assessed using the Cochrane RoB 2 tool. (Supplementary, Fig. S1) The meta -analysis was registered with PROSPERO (CRD420251112816). Findings Ten RCTs (n = 7,847 patients) met the inclusion criteria. Overall, ICIs did not significantly improve PFS compared to control treatments (HR 0.98, 95% CI 0.85–1.12; I2 = 67%). No significant benefit was observed in either first-line (HR 0.93) or recurrent settings (HR 1.07), nor in PD-L1–positive, BRCA-mutated, or homologous recombination deficiency (HRD) populations. A non-significant trend favouring ICI + PARP inhibitor combinations was observed in HR-proficient patients (HR 0.77, 95% CI 0.65–0.92). Sensitivity analyses confirmed the robustness of the findings. Overall survival (OS) data were either immature or not reported in most trials. The risk of bias was rated as low to moderate across studies, although there was high heterogeneity. Interpretation: Anti–PD-1/PD-L1-based ICI strategies have not led to significant improvements in outcomes for ovarian cancer. Future studies should focus on optimizing biomarker selection, evaluating combination therapies, and targeting the tumor microenvironment to enhance the efficacy of immunotherapy. Funding: This research received no external funding.