Efficacy and safety of PARP inhibitors in advanced or recurrent endometrial cancer patients: a systematic review and single arm meta-analysis

Background: Patients diagnosed with advanced or recurrent endometrial cancer have a poor prognosis, with few available treatment options. Poly (ADP-ribose) polymerase inhibitors (PARPi) have gained interest as a potential therapy for gynecological cancers. This single-arm meta-analysis aimed to evaluate the efficacy and safety of PARPi therapy in patients with advanced or recurrent endometrial cancer. Methods: The search strategy included PubMed, Cochrane, and Embase databases. Statistical analysis was performed using R software, applying the DerSimonian/Laird random-effects model for all analyses. Heterogeneity was evaluated using the I² statistic. Results: Our analysis included ten clinical trials comprising 345 patients with advanced or recurrent endometrial cancer. 81.2% (280/345) of patients received PARPi in combination with immune checkpoint inhibitors (ICI), angiogenesis inhibitors, and other drugs. Our pooled analysis demonstrated an overall objective response rate (ORR) of 20.59% (95% Confidence Interval (CI): 13.88–29.45) and a disease control rate (DCR) of 60.7% (95% CI: 46.53–74.87). ORR and DCR were better in combination treatment compared with monotherapy. The 6-month progression-free survival (PFS) and 12-month overall survival (OS) rates were, respectively, 27.51% (95% CI: 21.12–33.9) and 45.77% (95% CI: 38.21–53.33). The prevalence of adverse events of grades 3–5 were 44.24% (95% CI: 25.91–62.58). Conclusions: These findings suggest that PARPi may have potential in combination therapy for progressive endometrial cancer, but the current evidence is limited. Additional well-designed randomized studies are necessary to confirm these results and to develop more effective treatment strategies. The PROSPERO Registration: CRD42024535632.

PARP inhibitor therapy; Advanced or recurrent endometrial cancer; Immune checkpoint inhibitors; Angiogenesis inhibitors

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