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First-line maintenance niraparib (Zejula) was associated with longer progression-free survival (PFS) and overall survival (OS) among patients with homologous recombination deficiency (HRD)–positive advanced ovarian cancer vs those with HRD-negative disease following primary cytoreductive surgery (PCS) with no residual disease, according to data from a retrospective study presented in a poster session at the
At a median follow-up of 52 months (IQR, 48-55), median PFS from the start of niraparib was 54 months (95% CI, not estimable [NE]) in patients with HRD-positive tumors (n = 20) vs 14 months (95% CI, 3.5-24.5) in those with HRD-negative tumors (n = 20; P = .017). Progression or death occurred in 45% of patients in the HRD-positive group and 75% of patients in the HRD-negative group. In the overall analysis population (n = 40), median PFS was 28 months (95% CI, 0-56.4).
Median OS was not reached (95% CI, NE) in the HRD-positive group vs 37 months (95% CI, 19.46-54.5) in the HRD-negative group (P = .023). Deaths occurred in 20% and 60% of patients in the respective groups.
“Even in optimally debulked advanced ovarian cancers, niraparib showed favorable outcomes, particularly, but not limited to HRD-positive tumors,” wrote lead author Claudia Marchetti, MD, of Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, in Rome, Italy, and coinvestigators in the poster's conclusions.
Investigators retrospectively analyzed patients with advanced ovarian cancer who received niraparib through an expanded access program from 2020 to 2021 at Policlinico Gemelli in Rome after PCS with no residual disease and platinum-based chemotherapy. HRD status was determined with the Myriad Genetics proprietary algorithm. Somatic mutations, tumor mutational burden (TMB), and microsatellite instability were assessed with the TruSight Oncology 500 panel, and genomic data were extracted from final clinical reports. The primary end point was PFS from the start of niraparib.
Of 56 patients enrolled, 40 were molecularly evaluable and included in the analysis. Overall, 97% of patients had high-grade serous histology, and 67% had FIGO stage III disease.
HRD-positive and HRD-negative tumors each made up 50% of the molecularly evaluable population (n = 40), and 1 patient in the HRD-positive group had a BRCA1 mutation. TMB was low in 53% of tumors and intermediate to high in 47%. TP53 was the most frequently altered gene (92%), followed by ATM, KDM6A, CCNE1, PPP2R2A, PTEN, and MYC, each altered in 7.5% of tumors. All tumors were microsatellite stable.
The investigators designed the analysis to address a gap in the phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial (NCT02655016), which excluded patients with stage III disease and no residual disease after PCS and included few patients with stage IV disease and no residual disease. In PRIMA, median PFS with niraparib was 24.5 months in the HRD-positive population and 8.4 months in the HRD-negative population.
In June 2025, the FDA narrowed the first-line maintenance indication for niraparib to patients with HRD-positive advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer, defined by a deleterious or suspected deleterious BRCA mutation and/or genomic instability.2
According to the investigators, ongoing analyses of the complete sequencing data, extending beyond clinically reported variants, are expected to further refine the genomic profile of these tumors and identify biomarkers associated with response to niraparib.1
Disclosures: Marchetti reported receiving grants or contracts from AstraZeneca, MSD, Menarini, PharmaMar, and GSK; consulting fees from GSK, MSD, Clovis, AstraZeneca, Arquer Diagnostics, PharmaMar, and Menarini; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from GSK, MSD, Pharma&, AstraZeneca, Arquer Diagnostics, and PharmaMar; support for attending meetings and/or travel from Roche, AstraZeneca, and Eisai; and participation on a data safety monitoring board or advisory board for GSK, Pharma&, PharmaMar, AstraZeneca, and MSD.
