PARP inhibitors decrease response to subsequent platinum-based chemotherapy in BRCA mutated ovarian cancer patients

Objectives: To determine the impact of treatment with poly-adenosine ribose phosphatase inhibitors (PARPi) on the response to subsequent platinum-based chemotherapy in recurrent, platinum-sensitive BRCA-mutated epithelial ovarian, peritoneal, or fallopian cancer (BRCAm) patients. Methods: A retrospective, single-institution cohort study of patients with BRCAm who received treatment with multiple platinum regimens. Electronic medical records were reviewed to identify BRCAm patients who received subsequent platinum-based chemotherapy following PARPis from 12/15/2011-5/5/2020. Response to subsequent therapy and progression-free survival (PFS) was determined. The PFS of BRCAm patients was compared to non-BRCAm who were treated with platinum following a PARPi. Results: Among 241 BRCAm patients 152 recurred. One hundred and fifteen platinum sensitive BRCAm patients received a second-line platinum regimen with 108 being PARPi naive and 7 PARPi exposed. The median PFS was 2.4 times longer after 2nd line platinum-based therapy for patients who did not receive a PARPi, p=0.005. Fifty-five platinum-sensitive BRCAm patients received a third-line platinum regimen with 42 PARPi naive and 13 PARPi exposed. The median PFS was 2.3 times longer for 3rd line platinum regimens for BRCAm patients who did not receive a PARPi, p 24 months (Figure 2). The response and PFS to a platinum regimen following a PARPi were similar between BRCA mutated and non-mutated patients (Figure 3). Download : Download high-res image (63KB) Download : Download full-size image Conclusions: Among BRCAm patients, PARPi exposure significantly reduced PFS following 2nd and 3rd line platinum based chemotherapy. Prior exposure to PARPi nullifies well established predictors of response to subsequent platinum-based chemotherapy (platinum-free interval and BRCA mutational status. The routine use of PARP for maintenance should be questioned until PARPi overall survival data is mature. Download : Download high-res image (103KB) Download : Download full-size image