Efficacy and safety of immune checkpoint inhibitors in recurrent platinum-resistant ovarian cancer: A systematic review and meta-analysis of randomized controlled trials.

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Background: Recurrent platinum-resistant ovarian cancer (PROC) is associated with poor prognosis and limited therapeutic options. While immune checkpoint inhibitors (ICIs) have been investigated in various combinations, individual trials have shown inconsistent survival benefits. We performed a systematic review and meta-analysis to evaluate the pooled efficacy and safety of ICI-based regimens in PROC. Methods: Conforming to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search of MEDLINE, Embase, Cochrane Central, and Scopus was conducted. Randomized controlled trials (RCTs) evaluating ICIs (monotherapy or combinations) versus standard of care (SOC) in PROC were included. Primary outcomes were overall survival (OS) and progression-free survival (PFS), reported as hazard ratios (HR). Secondary outcomes included objective response rate (ORR) and grade ≥3 treatment-related adverse events (TRAEs), reported as risk ratios (RR). Data were pooled using a random-effects model. Heterogeneity was assessed using the I² statistic. Results: Eight RCTs (n = 3,656) were identified. Pooled analysis demonstrated a significant improvement in OS with ICI-based regimens compared to SOC (HR 0.88; 95% CI, 0.79-0.97; p = 0.01; I² = 0%). While the overall PFS did not reach significance (HR 0.85; 95% CI, 0.67-1.09; p = 0.20; I² = 78%), a sensitivity analysis excluding the NINJA trial (monotherapy outlier) revealed a significant PFS benefit (HR 0.77; 95% CI, 0.68-0.87; p < 0.0001; I² = 8%). In subgroup analyses, the combination of ICI plus chemotherapy significantly improved both OS (HR 0.83; 95% CI, 0.73-0.94) and PFS (HR 0.78; 95% CI, 0.67-0.91). Dual ICI therapy significantly improved PFS (HR 0.63; 95% CI, 0.42-0.94) and ORR (RR 2.95; 95% CI, 1.31-6.65). Safety analysis showed that ICI plus chemotherapy increased the risk of grade ≥3 TRAEs (RR 1.40; 95% CI, 1.10-1.78), whereas ICI monotherapy was associated with a lower risk of high-grade toxicity compared to chemotherapy (RR 0.29; 95% CI, 0.10-0.84). Conclusions: ICI-based therapies provide a significant survival benefit in patients with PROC, particularly when combined with chemotherapy. While these combinations increase the risk of high-grade toxicities, ICI monotherapy offers a better safety profile but lacks superior efficacy over standard chemotherapy.