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Immunotherapy with anti-PD-1 or PD-L1 in advanced ovarian cancer: A meta-analysis of randomized trials
Riccardo Vida1, Michele Bartoletti2, Marcella Montico3
1Unit of Medical Oncology and Cancer Prevention, Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy; Department of Medicine, University of Udine, Udine, Italy.
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.
Insights
Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 did not significantly improve progression-free survival in advanced ovarian cancer patients. Further research is needed to optimize immunotherapy strategies and combination therapies for better patient outcomes.
Area of Science:
- Oncology
- Immunotherapy
- Gynecologic Oncology
Background:
- Ovarian cancer has the highest mortality rate among gynecologic malignancies, with suboptimal survival despite treatment advances.
- Immune checkpoint inhibitors (ICIs) show biological promise, but their clinical effectiveness in ovarian cancer is uncertain.
- This study evaluates anti-PD-1/PD-L1 agents in advanced ovarian cancer using randomized trial data.
Purpose of the Study:
- To systematically review and meta-analyze randomized controlled trials (RCTs) assessing the efficacy of anti-PD-1/PD-L1 agents in advanced ovarian cancer.
- To determine if these agents improve progression-free survival (PFS) compared to standard treatments.
- To explore efficacy across different treatment settings and patient subgroups.
Main Methods:
- A systematic review and meta-analysis of RCTs were conducted, searching major databases and conference abstracts up to July 2025.
- Included studies compared anti-PD-1/PD-L1 agents (with or without chemotherapy) to standard treatments in advanced ovarian cancer.
- Progression-free survival (PFS) was the primary outcome, analyzed using a random-effects model to calculate pooled hazard ratios (HRs).
Main Results:
- Ten RCTs involving 7,847 patients were analyzed.
- Overall, ICIs did not significantly improve PFS versus control treatments (HR 0.98, 95% CI 0.85-1.12).
- No significant benefit was found in first-line, recurrent, PD-L1-positive, BRCA-mutated, or HRD populations, though a trend favored ICI + PARP inhibitor combinations in HR-proficient patients.
Conclusions:
- Current anti-PD-1/PD-L1-based ICI strategies do not significantly enhance outcomes in ovarian cancer.
- Future research should focus on improved biomarker selection for immunotherapy.
- Optimizing combination therapies and targeting the tumor microenvironment are crucial for improving ICI efficacy.
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