Emerging Therapeutic Synergies: Combining PD-1 Inhibitors With Poly-ADP-Ribose Polymerase (PARP) Inhibitors in the...

Gynecological cancers (ovarian, endometrial, cervical) remain a major cause of morbidity and mortality, driven by late presentation and resistance to standard therapies. Immune checkpoint blockade (PD-1/PD-L1) and PARP inhibition have each improved outcomes in biomarker-defined subsets. Preclinical data suggest synergy between these classes via PARP-induced DNA damage, cGAS-STING activation, and enhanced tumor immunogenicity, which may be amplified by PD-1/PD-L1 blockade. We performed a narrative review with a structured literature search of MEDLINE, Embase, and ClinicalTrials.gov (January 1, 2015, to August 24, 2025) for interventional trials evaluating a PARP inhibitor combined with an anti-PD-1/PD-L1 agent in ovarian, fallopian tube, primary peritoneal, endometrial, or cervical cancer. Eligibility required ≥1 efficacy endpoint (objective response rate {ORR}, progression-free survival {PFS}, and/or overall survival {OS}) plus safety in an extractable gynecology-only cohort (≥20 evaluable patients or any phase III). Triplets were eligible if the third agent was non-cytotoxic (e.g., bevacizumab). Regimens with concurrent cytotoxic chemotherapy in the investigational combination were excluded. Nine studies met the criteria (one phase III; eight phase I/II). In recurrent ovarian cancer, niraparib+pembrolizumab showed modest activity with durable responses in homologous recombination-deficient (HRD) tumors; olaparib+durvalumab demonstrated high activity in gBRCA platinum-sensitive relapse, and adding bevacizumab broadened benefit in non-BRCA cohorts. In the newly diagnosed disease, rucaparib+nivolumab maintenance failed to improve PFS versus rucaparib alone. Endometrial trials (olaparib+durvalumab; talazoparib+avelumab in mismatch repair-proficient disease) showed limited activity overall, with signals restricted to biomarker-selected subgroups. Toxicities reflected expected myelosuppression from PARP inhibitors and immune-related adverse events, generally manageable with standard algorithms. PARP+PD-1/PD-L1 combinations are most compelling in ovarian cancer, particularly in BRCA/HRD tumors and, in selected settings, with the addition of bevacizumab, while frontline maintenance benefit remains unproven and endometrial activity is modest. Biomarker-guided selection, rational triplets with non-cytotoxic partners, and optimized sequencing warrant further evaluation.