Effect of first-line poly(ADP-ribose) polymerase inhibitor on second-line platinum-based chemotherapy in epithelial...

Research on platinum sensitivity after poly(ADP-ribose) polymerase (PARP) inhibitor administration, which offers prognostic benefits for first-line treatment of advanced epithelial ovarian cancer (EOC), is limited. Here, we evaluated the impact of first-line maintenance therapy with PARP inhibitors on the efficacy of second-line platinum-based chemotherapy in patients with advanced EOC.

We retrospectively analyzed 100 patients with platinum-sensitive recurrent EOC who received second-line platinum-based chemotherapy between 2015 and 2024. The PARP inhibitor group included 35 patients who received PARP inhibitors as first-line maintenance, whereas the control group included 65 patients who did not. Overall response rate, post-recurrence progression-free survival (PFS), and post-recurrence overall survival (OS) were compared between the groups. Subgroup analyses were conducted using homologous recombination deficiency status and platinum-free interval (PFI).

The overall response rate was significantly lower in the PARP inhibitor group (25.7%) compared with the control group (89.2%, p<0.001). Median post-recurrence PFS and OS were significantly shorter in the PARP inhibitor group compared to that in the control group. In the PARP inhibitor group, homologous recombination deficiency-positive patients did not show better outcomes than homologous recombination deficiency-negative patients. Moreover, the overall response rate for patients with 6-12 months PFI was particularly poor in the PARP inhibitor group.

First-line PARP inhibitor maintenance therapy may reduce the efficacy of subsequent platinum-based chemotherapy, potentially inducing platinum resistance. These findings highlight the need to reconsider treatment strategies and predictive biomarkers for second-line therapy following PARP inhibitor exposure in relapsed EOC.