Immune checkpoint inhibitors in clear cell ovarian carcinoma and mixed gynecologic clear cell cohorts: a systematic review and meta-analysis.

[OBJECTIVE] Clear cell ovarian carcinoma is a rare sub-type characterized by poor prognosis and intrinsic resistance to platinum-based chemotherapy. Unlike high-grade serous ovarian cancer, its distinct molecular profile suggests a potentially greater susceptibility to immunotherapy. However, available evidence remains limited and heterogeneous. This systematic review and meta-analysis evaluated the efficacy and safety of immune checkpoint inhibitors in this setting.

[METHODS] PubMed, Embase, and Cochrane databases were searched through November 2025. Cohort studies and clinical trials enrolling patients with clear cell ovarian carcinoma alone or mixed ovarian and endometrial clear cell carcinoma were eligible. Immune checkpoint inhibitors administered as monotherapy or in combination with other systemic therapies were included. Outcomes were objective response rate, progression-free survival, overall survival, and treatment-related adverse events, including any-grade and grade ≥3 events. A random-effects model was used for pooled analyses with R software version 4.2.0. The study was registered in International Prospective Register of Systematic Reviews (CRD420251130819).

[RESULTS] Fifteen studies (423 patients), including 14 clinical trials and 1 cohort study, met eligibility criteria. The pooled objective response rate across all treatment cohorts was 24.5% (95% confidence interval [CI] 18.3 to 32.7, I = 61%, p < .01). Specifically, 14.6% for immune checkpoint inhibitor monotherapy (n = 122, 95% CI 8.8 to 24.2, I = 38%, p = .15) and 37.5% for dual blockage (n = 77, 95% CI 24.4 to 57.5, I = 42%, p = .16). Four studies (n = 130) provided re-constructable survival data, yielding a pooled median progression-free survival of 3.8 months and overall survival of 18.8 months. Severe treatment-related adverse events grade ≥3 occurred in 29.36% of patients (N = 288, 95% CI 20.30 to 42.47, I = 70%).

[CONCLUSIONS] Immune checkpoint inhibitors demonstrate modest clinical activity in clear cell gynecologic carcinomas, with higher response rates observed for dual agent. Treatment-related adverse events were frequent, underscoring the need for careful patient selection and toxicity monitoring. Substantial heterogeneity and limited survival data support the need for biomarker-driven prospective trials to better define which patients benefit the most.