Correlation between BRCA 1 / 2 pathogenetic mutations and response to Poly (ADP-Ribose) Polymerase inhibitors (PARPi) has been fully investigated and amply recognized in ovarian cancer (OC) patients. Moreover, data about clinical implication of variant of unknown significance (VUS) are lacking. The aim of this study was to evaluate differences in survival outcomes in BRCA 1 / 2 pathogenetic mutated, VUS and wild type (WT) relapsed OC patients treated with PARPi.
In this retrospective case control study OC patients, whose BRCA 1 / 2 genetic tests were available and receiving PARPi as maintenance at the time of first relapse between 2014 and 2021, were included. Patients were divided into three groups according to BRCA mutational status (BRCA 1 / 2 pathogenetic mutated, VUS and WT). Clinical characteristics at baseline and at the time of relapse before PARPi therapy were evaluated and progression free survival (PFS), defined as the time between date of last platinum and date of progression during PARPi or last follow-up, were assessed in each study group.
Out of 67 patients identified, 24 (35.8%), 20 (29.9%) and 23 (34.3%) presented with BRCA 1 / 2 mutation, VUS and BRCA WT, respectively. In the overall population, most patients were diagnosed at an advanced stage, with 82.1% (n=55) at stage III and 8.9% (n=6) at stage IV. Median age at the time of first recurrence before PARPi was 58 years (Interquartile Range 55-61). Patients received Olaparib, Niraparib and Rucaparib as maintenance at the time of fist relapse after complete or partial response to platinum-based chemotherapy and no statistically significant differences were found in previous Platinum Free Interval (PFI) among the analyzed groups. Median PFS of BRCA 1 / 2 pathogenetic mutated patients was significantly longer than patients BRCA WT or VUS (Not Reached versus 4 months vs 7 months, respectively; p<0.001). Additionally, no significant difference was found between BRCA WT and BRCA VUS (p = 0.50).
Our study suggests that BRCA VUS carriers present survival outcomes comparable with BRCA 1 / 2 wild type patients and with shorter PFS than women harboring BRCA 1 / 2 pathogenetic mutations.
The authors.
Has not received any funding.
C. Marchetti: Financial Interests, Personal, Other: GSK; Financial Interests, Personal, Other: Clovis Oncology; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: PharmaMar. V. Salutari: Financial Interests, Personal, Other: GSK; Financial Interests, Personal, Other: PharmaMar; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: Eisai; Financial Interests, Personal, Other: Clovis; Financial Interests, Personal, Other: AstraZeneca. S. Pignata: Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal, Other: Clovis; Financial Interests, Personal, Other: GSK; Financial Interests, Personal, Other: PharmaMar; Financial Interests, Personal, Sponsor/Funding: MSD; Financial Interests, Personal, Sponsor/Funding: Roche; Financial Interests, Personal, Sponsor/Funding: AstraZeneca; Financial Interests, Personal, Sponsor/Funding: Pfizer. G. Scambia: Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Other: Clovis Oncology; Financial Interests, Personal, Other: Tesaro; Financial Interests, Personal, Other: Johnson & Johnson. D. Lorusso: Financial Interests, Institutional, Sponsor/Funding: Clovis; Financial Interests, Institutional, Sponsor/Funding: GSK; Financial Interests, Institutional, Sponsor/Funding: MSD; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Clovis; Financial Interests, Personal, Other: GSK; Financial Interests, Personal, Other: PharmaMar; Financial Interests, Personal, Other: MSD; Financial Interests, Personal, Other: Genmab; Other, Personal, Member of the Board of Directors: GCIG. All other authors have declared no conflicts of interest.