Recurrent ovarian cancer: maintenance treatment with PARP inhibitors in clinical practice

Abstract

Objectives: In clinical trials maintenance treatment with PARP inhibitors (PARPi) improved progression-free survival with manageable toxicity in platinum-sensitive recurrent ovarian cancer (PSROC). In this study we review the impact of olaparib (reimbursed in Portugal for BRCA patients [pts] exclusively) and niraparib (prescribed for non-BRCA pts) in PSROC. Methods: Descriptive review of outcomes for all pts with PSROC, treated with PARPi in our center. Pts started treatment on March 2016 (Olaparib) and February 2019 (Niraparib). Results: From March 2016 to June 2020 Olaparib and Niraparib were used as maintenance treatment in 49 pts, 20 BRCAmt and 29 BRCAwt, respectively. Median age for all pts was 64 years (36-82), the difference between BRCA and non-BRCA pts (60.5 versus 65 years) being non-significant (p=0.28). All pts had high-grade serous carcinoma, 79.6% had cancer stage IIIC-IVB at diagnosis and all were primarily treated with cytoreductive surgery and platinum-based chemotherapy. Residual disease after primary surgery was present in 35% BRCA pts and 62,1% nonBRCA pts (p=0.0457). Olaparib was prescribed for maintenance after the first (15pts), second (2pts), third (1 pt) and fourth recurrence (3pts). Medium treatment duration was 13,7 months (0.97-44,8). At the time of this analysis, 50% of pts (10) were still having benefit from treatment (either stabilization or improvement of the previous tumor objective response after platinum) and 60% (8 BRCA2, 4 BRCA1) of pts were classified as Long Term Responders (>12 months) (LTR). Among LTR, 4 BRCA2 pts maintained treatment benefit for more than 2 years (one is on treatment 25.3 months after her 4th relapse). No association was observed between LTR and complete or partial response to previous platinum (p=0,55). Disease progression or death was observed in 10/20 with TTDST (time to death or subsequent treatment) being 10.49 months (0.96-23.77). One pt died from an unknown cause. Niraparib was prescribed for maintenance after the first (16pts), second (7pts) and third (6pts) recurrence. Median treatment duration was 3,7 months (0.13 - 13,3). At the time of analysis 18/29 pts (62%) were still having benefit from treatment. One LTR was identified and 3/6 pts are still on treatment after the 3rd recurrence (median treatment duration 6,5 months). Disease progression was observed in 11 pts (45% of which were on maintenance after 1st recurrence) and 5 pts died, with TTDST being 4.5 months (1,9-13,3). At least one adverse event was reported in 91,8% of patients, the most common being anemia (70%) and nausea and vomiting (35%) with olaparib and asthenia (55,2%), anemia (37,9%) and thrombocytopenia (34,5%) with niraparib. Dose reductions were observed in 26/49 pts (10 pts with olaparib and 16 pts with niraparib); 7 of which underwent a second dose reduction (2 pts with olaparib and 5 pts with niraparib). Anemia and thrombocytopenia were the main reasons for dose reductions for olaparib and niraparib, respectively. Conclusions: Benefit from PARPi maintenance for PSROC was observed, even after 3 and 4 previous lines of platinum treatment. Assuming a pharmacological class effect for the two interventions, our data also confirms that even if effectiveness is not restricted to the BRCA population, these pts derive more benefit from PARPi maintenance, with BRCA2 pts predominating among the LTR subgroup. Further prospective follow up is ongoing.