Ryon P. Graf

Effectiveness of PARP Inhibitor Maintenance Therapy in Ovarian Cancer by BRCA1/2 and a Scar-Based HRD Signature in Real-World Practice

Abstract Purpose: The purpose of the study was to compare the effectiveness of PARP inhibitor maintenance therapy (mPARPi) in real-world practice by biomarker status [BRCA1/2 alterations (BRCAalt) and a homologous recombination deficiency signature (HRDsig)] in advanced ovarian cancer. Experimental Design: Patients with ovarian cancer receiving first-line platinum-based chemotherapy and either mPARPi or no maintenance were included. Patient data were obtained by a US-based de-identified ovarian cancer Clinico-Genomic Database, from ∼280 US cancer clinics (01/2015–03/2023). Real-world progression-free survival (rwPFS) and overall survival (rwOS) were compared by biomarker status using Cox models, weighted by propensity scores. Results: Of 673 patients, 160 received mPARPi [31.2% BRCAalt and 51.9% HRDsig(+)] and 513 no maintenance [15.6% BRCAalt and 34.1% HRDsig(+)]. BRCAalt patients receiving mPARPi versus no maintenance had favorable rwPFS [HR, 0.48; 95% confidence interval (CI), 0.26–0.87; P = 0.0154], as did BRCA wild-type (WT; HR, 0.76; 95% CI, 0.57–1.01; P = 0.0595). Favorable rwOS was not observed with mPARPi for BRCAalt or BRCA-WT. HRDsig(+) patients receiving mPARPi versus no maintenance had favorable rwPFS (HR, 0.36; 95% CI, 0.24–0.55; P < 0.001) and numerically favorable rwOS (HR, 0.46; 95% CI, 0.21–1.02; P = 0.0561). No differences were observed for HRDsig(−). mPARPi treatment interaction was observed for HRDsig(+) versus HRDsig(−) (rwPFS P < 0.001/rwOS P = 0.016) but not for BRCAalt versus BRCA-WT. Patients with BRCA-WT/HRDsig(+) receiving mPARPi had favorable rwPFS (HR, 0.40; 95% CI, 0.22–0.72; P = 0.003), whereas no difference was observed for BRCA-WT/HRDsig(−). Conclusions: HRDsig predicted benefit of mPARPi better than BRCAalt. Patients with HRDsig(+) status experienced favorable outcomes, even if they had BRCA-WT status. In contrast, patients with HRDsig(−) status did not show significant benefit from mPARPi treatment. HRDsig might predict benefit from mPARPi regardless of BRCAalt status.