First-line immunotherapy with or without PARP inhibitors in advanced ovarian cancer: A meta-analysis including...

Despite response to up-front treatment, patients with ovarian cancer remain at high risk of recurrence, with poor survival. Immunotherapy plus chemotherapy, alone or in combination with poly(ADP-ribose) polymerase inhibitors (PARPi) or VEGF inhibitors, has been investigated in ovarian cancer, with heterogeneous results.

A meta-analysis of randomized phase III trials was conducted. PubMed, EMBASE, ClinicalTrials.gov, and congress proceedings were systematically searched. Two comparisons were performed: i) mono-immunotherapy throughout and the relative control arm; ii) immunotherapy plus PARPi and the relative control arm. The primary endpoint was the progression-free survival (PFS) and was analyzed in the overall population and by bevacizumab use, BRCA/homologous recombination deficiency (HRD) status, and PD-L1 expression.

Six trials, involving 6465 patients, were analyzed. In the overall population, immunotherapy did not affect PFS, alone [Hazard ratio (HR) 0.94, 95% Confidence Interval (CI) 0.85-1.05] or with PARPi (HR 0.83, 95% CI 0.62-1.12). Potential benefits are suggested in selected populations. Immunotherapy plus PARPi and bevacizumab significantly improved PFS (HR 0.71, 95% CI 0.58-0.85). A PFS benefit was observed in the HRD-positive, BRCA wild-type and PD-L1-negative populations receiving immunotherapy plus PARPi (HR 0.71, 95% CI 0.52-0.97 and HR 0.72, 95% CI 0.57-0.91, respectively) compared to control groups. Mono-immunotherapy showed a slight advantage in HRD-negative patients (HR 0.87, 95% CI 0.78-0.98).

In first-line treatment of advanced ovarian cancer, immunotherapy ± PARPi does not provide PFS benefits in unselected patients. However, efficacy signals in specific subgroups support the need for biomarker-driven strategies and optimized trials.