Maintenance therapy with a poly(ADP-ribose) polymerase inhibitor (PARP) in patients with newly diagnosed ovarian cancer: A systematic review and meta-analysis.

Abstract

e17587 Background: PARP inhibitors (PARPi) have been approved for maintenance therapy in newly diagnosed ovarian cancer patients with or without homologous recombination deficiency (HRD). In this meta-analysis, the latest clinical data to assess the efficacy and safety of this approach across different subgroups were synthesized. Methods: PubMed, Scopus, and Cochrane databases were searched for randomized controlled trials that compared maintenance PARPi with placebo in newly diagnosed ovarian cancer. The outcomes of interest included progression-free survival (PFS) according to HRD status, overall survival (OS), second PFS (PFS2), and time-to-first subsequent treatment (TFST). Heterogeneity was examined with I2 statistics. A random-effects model was used for outcomes with high heterogeneity. Results: A total of 6 Randomized clinical trials with 3609 patients were included, of whom 2348 (65%) received maintenance PARPi. PFS was significantly longer for HRD-positive patients receiving PARPi [Hazard ratio (HR) 0.44, 95% Confidence interval (CI) 0.37 – 0.52 p<0.001] and for HRD-negative patients [HR 0.71, 95% CI 0.54 – 0.92 p=0.009]. Maintenance PARPi was associated with improved OS in HRD-positive patients [HR 0.59, CI 0.47 -0.73, p<0.001] but not in unselected patients. PFS2 in the HRD-positive population was reported in three trials, and it favored the use of PARPi [HR 0.57, CI 0.43 – 0.76, p<0.001]. Adverse events ≥grade 3 were more common in patients on maintenance PARPi (p<0.001). The occurrence of myelodysplastic syndrome was numerically but not significantly higher in the PARPi group. Conclusions: Maintenance with PARPi in patients with newly diagnosed ovarian cancer significantly prolongs PFS regardless of HRD status. Moreover, PARPi maintenance improves OS and PFS2 in patients with BRCA and/or HRD-positive tumors compared to placebo. [Table: see text]