Survival outcomes in patients withBRCAmutated, variant of unknown significance, and wild type ovarian cancer treated with PARP inhibitors

Abstract

ObjectiveCorrelation betweenBRCA1/2 (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 withBRCAvariants of unknown significance, mutated, and wild type relapsed ovarian cancer treated with PARPi.MethodsPatients with ovarian cancer whose somaticBRCAtesting 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 toBRCAmutational status (variant of unknown significance, mutated, and wild type). Progression-free survival was assessed in each study group.ResultsOf 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 withBRCAmutation 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 withBRCAwild type andBRCAvariant of unknown significance (p=0.50).ConclusionOur study suggests that carriers of BRCA variant of unknown significance have survival outcomes comparable to patients withBRCAwild type and shorter progression-free survival than women harboringBRCApathogenic variants.