Real-world analysis of survival outcomes and toxicities with PARPi use across indications

Abstract

Objectives: Poly (ADP-ribose) polymerase inhibitors (PARPis) improve progression-free survival (PFS) in high-grade epithelial ovarian cancer (EOC) as frontline maintenance (FM), platinum sensitive maintenance (PSM) and active therapy (AT) of recurrence. Investigation of PARPi effectiveness within everyday clinical practice is necessary. Using real-world PARPi data we explored survival outcomes by PARPi indication (PI), toxicities and impact on next-line therapy. Methods: A retrospective review was conducted of EOC patients receiving PARPis from 3/2014-3/2020. Medical records were reviewed for clinicopathologic data, PI, treatment details, response, survival and toxicity. Statistics included descriptive, one-way ANOVA, Cox proportional hazard (PH) regression and Wilcoxon Gehan-Breslow survival analyses. Results: 175 patients were included. Mean age at diagnosis was 59.9 years (25.8-93). Most patients had high-grade serous histology (88%), advanced stage (III 62.9%; IV 23.4%) and platinum sensitive disease (84.6%). BRCA status included 54 (30.9%) germline, 5 (2.9%) somatic, 6 (3.4%) homologous recombination deficient and 88 (50.3%) negative. PI included FM (11.4%), PSM (41.7%) and AT (46.9%). PI predicted PFS on PARPi [median (months): FM=18.2, PSM=19.3, AT=6.3, p=0.0001]. On Cox PH regression, age (p=0.03), PI (p=0.001) and PARPi agent (p=0.003) predicted PFS. Of 123 patients with progression (FM=8, PSM=43, AT=72), 97 (78.9%) received next-line therapy including chemotherapy (73.2%), clinical trial (11.3%), VEGF inhibition (5.2%), immune therapy (5.2%), hormones (4.1%) and HIPEC (1.0%). Disease control rate on next-line was 43.3% (Figure 1). PI was not associated with PFS on next-line [median (months): FM=3.5, PSM=3.8, AT=4.4, p=0.48] or number of subsequent lines (mean, FM=1.8, PSM=2.3, AT=2.1, p=0.21). PI predicted overall survival (OS) [median (months): FM-not met, follow-up=27.6, PSM-not met, follow-up=65.7, AT=78.0, p Download : Download high-res image (70KB) Download : Download full-size image Conclusions: PARPi toxicities reflected clinical trial results. Across indications PARPi use did not limit administration or response to subsequent therapies, though patients receiving next-line cytotoxic had notable hematologic toxicity. PFS on PARPi and OS were associated with PI. Future research should aim to identify optimal sequencing of PARPi, and those most likely to benefit from retreatment.