A US real-world study of second-line outcomes in advanced ovarian cancer by first-line PARP inhibitor maintenance exposure.

Abstract

e17564 Background: As PARPi maintenance (MTx) is widely used after first-line (1L) platinum-based therapy for advanced ovarian cancer (aOC), understanding its impact on subsequent platinum (PLT) sensitivity is critical. This real-world (rw) study described characteristics of aOC patients who received second-line (2L) therapies after 1L PARPi MTx or 1L PLT and evaluated 2L outcomes with 2L PLT versus non-platinum (no-PLT) therapies. Methods: This retrospective cohort study used chart review data from The US Oncology Network electronic medical records. Adult women with Stage III–IV OC initiating 2L systemic treatment (index date) between 1-Jan-2017 and 1-May-2023 following progression after 1L PARPi or 1L PLT were included, with follow-up to 31-Oct-2023. Descriptive statistics were used to summarize patient characteristics and treatment patterns. Kaplan-Meier analysis was used to assess rw treatment-free interval (rwTFI) after 2L treatment, rw platinum-free interval (rwPFI) after 2L PLT, rw progression-free survival (rwPFS), and overall survival (OS) from index date. Results: A total of 165 patients received 2L therapy after 1L PARPi MTx (PARPi cohort) and 83 PARPi-naïve patients received 2L therapy after 1L PLT (PARPi-naïve cohort), selected via stratified random sampling. In the PARPi cohort, 20% (n=33) were PLT resistant (PROC, progressed 1-6 months [mo] after 1L PLT), and 64.2% (n=106) were PLT sensitive (PSOC, progressed >6 mo after 1L PLT), most of whom progressed after PARPi (n=101) and only 5 progressed while on PARPi. In the PARPi cohort, median 2L rwTFI was 1.6 mo with 2L PLT and 1.3 mo with 2L no-PLT; in the PARPi-naïve cohort, median 2L rwTFI was 4.7 mo with 2L PLT and 1.0 mo with 2L no-PLT. Table 1 reports medians and 95% confidence intervals (CIs) of 2L outcomes in each cohort by 2L PLT use by PSOC and PROC. Conclusions: This analysis showed a pattern of numerically more favorable outcomes with 2L PLT than no-PLT, with greater benefit in 1L PARPi-naïve versus PARPi-exposed patients. These descriptive, hypothesis-generating findings suggest that 1L PARPi MTx may impact 2L outcomes, including effectiveness of 2L PLT, regardless of PLT sensitivity, underscoring the need for novel therapies and personalized approaches for patients previously exposed to PARPi. 2L median outcomes in months (95% CI) 1L PARPi MTx PSOC 2L PLT No 2L PLT PROC 2L PLT No 2L PLT 1L PARPi-naive PSOC 2L PLT No 2L PLT PROC 2L PLT No 2L PLT n 79 27 10 23 30 8 9 20 rwTFI 2.0 (1.4,3.2) 1.1 (0.7,2.6) 0.9 (0.0,1.8) 1.5 (1.0,2.1) 5.4 (1.0,8.3) 0.9 (0.1,NR) 1.4 (0.7,NR) 1.1 (0.7,1.4) rwPFI 2.1 (1.0,4.1) NA 0.9 (0.1,2.2) NA 2.6 (0.7,8.3) NA 2.5 (0.7,NR) NA rwPFS 8.3 (7.3,11.5) 5.6 (2.9,6.5) 6.4 (1.2,8.8) 3.7 (1.9,5.2) 9.7 (6.1,18.0) 4.1 (1.8,NR) 8.1 (2.8,15.5) 2.5 (1.9,5.8) OS 20.4 (15.6,34.6) 18.8 (10.6,29.8) 12.3 (1.5,NR) 9.7 (5.7,19.4) 23.2 (13.6,NR) 28.5 (1.8,NR) 15.7 (9.0,NR) 12.2 (3.1,20.5) NA=not available; NR=not reached.