Chemotherapy and PARP inhibitors in heavily pretreated BRCA1/2 mutation ovarian cancer (BMOC) patients.

Abstract Objectives The hallmarks of germline(g) and/or somatic(s) BRCA1/2 mutation ovarian cancer (BMOC) patients are increased sensitivity to platinum-based chemotherapy (PCT) and PARP inhibitors (PARPi). There is little information on the effectiveness of chemotherapy in heavily pretreated (≥3 CT lines) g/sBMOC patients. Methods g/sBMOC patients who received CT from 2006 to 2016 at 4 cancer centers in Spain were selected. Overall survival (OS) and time to progression (TTP) were calculated with Kaplan Meier and Cox models. Results 135 g/sBMOC patients were identified (6% s BRCA1 / 2 mutations). The median number of chemotherapy lines was 2 (1–7). The 6-years OS rate was 69.4% and 71% in BRCA1 or BRCA2 mutation carriers (p = 0.98). A total of 57 (42%) patients had ≥3 CT lines (3–7), which encompassed a total of 155 treatments. The median overall TTP across all treatment lines beyond 2nd line was 10.2 months (CI 95% 8.4–11.9 months). In the platinum-sensitive setting, TTP was improved with PCT plus PARPi (17.1 m), PCT (12.6 m) or PARPi (12.4 m) versus non-PCT (4.9 m; p < 0.001 all comparisons). In the platinum-resistant setting, these differences in TTP were not statistically significant. A multivariate model confirmed that primary platinum-free interval (PFI) > 12 months and exposure to PCT and PARPi associated with improved outcomes. PARPi exposure did not compromise benefit of subsequent CT beyond 2nd relapse. Conclusions Heavily pretreated g/sBMOC demonstrated CT sensitivity, including for non-PCT choices. Primary platinum-free interval (PFI) >12 months and exposure to both platinum-based chemotherapy and PARPi associate with improved prognosis in heavily pretreated g/sBMOC patients. Highlights • Heavily pretreated g/sBMOC patients remain responsive to chemotherapy in the refractory setting. • Primary platinum-free interval is a strong predictor of the outcome of heavily pretreated g/sBMOC patients. • Exposure to both platinum-based chemotherapy and PARPi correlates with TTP in heavily pretreated g/sBMOC patients. • Our data provide benchmarks for design and interpretation of trials in recurrent disease. [ABSTRACT FROM AUTHOR]