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. 2025 Jul 4;30(7):oyae330.
doi: 10.1093/oncolo/oyae330.

Germline BRCA pathogenic variants and hematologic adverse events in patients with ovarian carcinoma receiving PARP inhibitors: a retrospective cohort study

Carmine Valenza  1   2 , Eleonora Nicolò  1   2 , Marta Mongillo  3 , Dario Trapani  1   2 , Jalissa Katrini  1   2 , Laura Boldrini  1   2 , Luca Boscolo Bielo  1   2 , Grazia Castellano  1   2 , Lorenzo Guidi  1   2 , Gloria Pellizzari  1   2 , Jacopo Villa  4 , Silvia Derio  3 , Mariateresa Lapresa  3 , Federica Gigli  5 , Gabriella Parma  3 , Emanuela Omodeo Salè  4 , Enrico Derenzini  5 , Giuseppe Curigliano  1   2 , Nicoletta Colombo  3   6
Affiliations

Germline BRCA pathogenic variants and hematologic adverse events in patients with ovarian carcinoma receiving PARP inhibitors: a retrospective cohort study

Carmine Valenza et al. Oncologist. .

Abstract

Background: Patients with a germline BRCA pathogenic variant (gBRCA-PV) and advanced high grade ovarian carcinoma (aHGOC) experience higher hematologic adverse events (HAEs) when receiving platinum salts and ionizing radiations, compared to non-carriers, due to a possible higher susceptibility of the hemopoietic stem cells to DNA targeting agents. However, the incidence of PARP inhibitor (PARPi)-related HAEs according to the gBRCA-PV status is currently unknown.

Patients and methods: We conducted a single-center retrospective cohort study to describe the occurrence of HAEs in patients with aHGOC receiving ≥8 weeks of maintenance PARPi in any line of therapy, comparing gBRCA-PVs carriers to non-carriers. HAEs were manually identified by searching the patients' electronic medical records and classified by CTCAE v5.0. The main endpoint was the incidence rate of any HAE (ie, anaemia, neutropenia, or thrombocytopenia) of grade 2 or more (G ≥ 2).

Results: One hundred and sixty-six patients were included; 95 (57%) had a gBRCA-PV. In total, 162 incident cases of G ≥ 2 HAEs were reported over 255.3 person-years. The incidence rates of G ≥ 2 HAEs were 1003/1000 person-years in gBRCA-PV carriers and 993/1000 person-years in non-carriers. No difference in the incidence rate of G ≥ 2 HAEs emerged comparing gBRCA-PV carriers to non-carriers (crude-incidence rate ratio [IRR]: 1.01; 95% CI: 0.72, 1.43; P = .96), even after adjusting for the type of PARPi (Mantel-Haenszel IRR: 0.99; 95% CI: 0.67, 1.46).

Conclusion: Patients with aHGOC and a gBRCA-PV do not experience higher PARPi-related HAEs compared to non-gBRCA-PV carriers, unlike platinum salt-related HAEs.

Keywords: PARP inhibitors; advanced high-grade ovarian carcinoma; germline BRCA pathogenic variants; hematologic adverse events.

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Conflict of interest statement

N.C. reports institutional research funding from Clovis Oncology; serving in a consulting or advisory role for Clovis Oncology, AstraZeneca, BIOCAD, Eisai, GlaxoSmithKline, Immunogen, Merck Sharp & Dohme, Mersana, Novartis, Nuvation Bio, Oncxerna, Pfizer, PharmaMar, Roche, and Tesaro; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Clovis Oncology, AstraZeneca, GlaxoSmithKline, Merck Sharp & Dohme, and Novartis; and support for attending meetings and/or travel from AstraZeneca. G.C. reports financial interests with AstraZeneca, Celcuity, Daiichi Sankyo, Exact Sciences, Lilly, Merck, Novartis, Pfizer, Roche, Veracyte, Ellipsis, Astellas, Blueprint Medicine, BMS, Kymab, Merck, Novartis, Philogen, Relay Therapeutics, Sanofi; and non-financial interests with the Italian National Health Council as Advisor for Ministry of Health ESMO, ESMO as Clinical Practice Guidelines Chair, Europa Donna as Member of the Scientific Council, EUSOMA as member of the Advisory Council, Fondazione Beretta, Lega Italiana Lotta ai Tumori as member of Board of Directors. All the competing interests were outside the submitted work. E.D. reports and research funding from ADC Therapeutics and Takeda, consulting fees from Roche, Beigene, Abbvie, AstraZeneca, and Takeda, payments or honoraria from Abbvie, Roche, Incyte, and Beigene, support for meetings and/or travel from Abbvie and Beigene, a Data Safety Monitoring Board or Advisory Board role with Abbvie, Beigene, Takeda, and Roche, and the receipt of equipment, materials, drugs, medical writing, gifts or other services from ADC Therapeutics. All other authors have no potential conflicts of interest to disclose.

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