Objective Correlation between BRCA1/2 (BRCA) pathogenic variants and the response to poly (ADP-ribose) polymerase inhibitors (PARPi) has been recognized in patients with ovarian cancer. Moreover, data on the clinical implications of variants of unknown significance are lacking. The aim of this study was to evaluate differences in survival outcomes in patients with BRCA variants of unknown significance, mutated, and wild type relapsed ovarian cancer treated with PARPi.
Methods Patients with ovarian cancer whose somatic BRCA testing was available and who were receiving PARPi as maintenance treatment at the first recurrence between January 2014 and January 2021 were included in the present study and analyzed. Patients were divided into three groups according to BRCA mutational status (variant of unknown significance, mutated, and wild type). Progression-free survival was assessed in each study group.
Results Of 67 patients identified, 20 (29.9%), 24 (35.8%), and 23 (34.3%) had BRCA variant of unknown significance, mutated, and wild type, respectively. Patients received PARPi as maintenance treatment at the time of the first relapse after a complete response or partial response to platinum-based chemotherapy without differences in the previous platinum-free interval among the analyzed groups. The median progression-free survival of patients with BRCA mutation was significantly longer than for those with BRCA wild type or variant of unknown significance (not reached vs 4 months vs 7 months, respectively; p<0.001). Additionally, no significant difference was found between patients with BRCA wild type and BRCA variant of unknown significance (p=0.50).
Conclusion Our study suggests that carriers of BRCA variant of unknown significance have survival outcomes comparable to patients with BRCA wild type and shorter progression-free survival than women harboring BRCA pathogenic variants.
- ovarian cancer
- BRCA1 protein
- BRCA2 protein
Data availability statement
Data are available upon reasonable request.
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Presented at This research was presented in the poster section during the ESMO GYN meeting in June 2022.
Contributors Conceptualization DL. Data curation: LM, SB. Formal analysis: CM. Investigation: LM, SB. Methodology: LM, SB, DL. Project administration: DL. Supervision: DL. Writing original draft: LM. Responsible for the overall content as guarantor: DL. All authors acquired data and revised and approved the final version of the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests CM reports consultant/advisory board for Clovis, Pharmamar, GSK, AstraZeneca, Arquer Diagnostic and travel accommodation from PharmaMar and Roche. VS reports honoraria from GSK, PharmaMar, Roche, MSD, EISAI, Clovis, Oncology, AstraZeneca. SP reports honoraria from AstraZeneca, MSD, Roche, Pfizer, Clovis, GSK, PharmaMar and research funding from MSD, Roche, AstraZeneca and Pfizer. GS reports research support from MSD and honoraria from Clovis Oncology. Consultant for Tesaro and Johnson & Johnson. DL reports research funding from Clovis, GSK and MSD, personal interests with AstraZeneca, Clovis Oncology, GSK, PharmaMar, MSD and financial interests with Clovis, Genmab, GSK, MSD. Board of Directors, GCIG (Gynecologic Cancer Inter Group).
Provenance and peer review Not commissioned; externally peer reviewed.