Retrospective analyses show a lower-than-expected response to subsequent chemotherapy in recurrent platinum sensitive BRCA mutated OC patients who received a maintenance poly-adenosine ribose phosphatase inhibitor (PARPi). Does PARPi use affect real world outcomes for OC patients including BRCA wild-type?
We undertook a retrospective single-institution analysis of medical records for patients who received subsequent chemotherapy following a PARPi between January 2018-December 2021. Objective Response Rate (ORR), Disease Control Rate (DCR), Progression Free Survival (PFS) and Overall Survival (OS) were calculated. Statistical tests used were Kaplan-Meier (OS and PFS) and Fisher’s Exact Test (DCR and ORR).
We included 46 patients; mainly advanced stage III (n = 29, 63%) and IV (n = 16, 35%). Most were germline BRCA wild-type (n = 42, 91%) with 4 (9%) germline BRCA mutant. PARPi’s included olaparib (n = 2, 4%), niraparib (n = 37, 80%) and rucaparib (n = 7, 15%), with median duration of use of 150 days (range 9-630). Longer duration on PARPi showed a trend to progression at next treatment (non-significant). Subsequent post-PARPi chemotherapy was mainly platinum-based (n=39, 85%).
ORR to first post-PARPi treatment was 23% for a platinum-based (non-evaluable radiological response excluded 4 patients) and 0% for non-platinum chemotherapy (p = 0.31). DCR was 31% to platinum-based and 14% to non-platinum chemotherapy (p = 0.65). Median PFS was 5.0 months for platinum-based and 1.3 months for non-platinum chemotherapy (HR 0.65, p = 0.31). Median OS was 17 months for platinum-based and 10.7 months for non-platinum chemotherapy (HR 0.15, p < 0.008).
Stratification by previous platinum-free interval (PFI) of 6-12 months (n = 13), 12-24 months (n = 11) and >24 months (n = 12) showed no significant difference in ORR (p = 0.89), DCR (p = 0.90), PFS (p = 0.29) or OS (p = 0.79) following first post-PARPi treatment. Limitations include single institution experience and retrospective non-trial based follow up.
Maintenance PARPi use resulted in similar PFS, ORR and DCR to subsequent treatment when compared to historic studies in the BRCA wild-type population and was not affected by PFI.