Abstract 56P
Background
Ovarian cancer (OC) is an aggressive tumour that is usually diagnosed in an advanced stage. The presence of somatic and/or germinal mutations in the genes BRCA1 and BRCA2 is known to be predictive of response to platinum agents and inhibitors of PARP (iPARP). Nevertheless, in recent years it has been shown that the efficacy can vary according to the specific mutation. In our community there is a high prevalence of patients (pts) carrying the BRCA1 c.211 A>G germline pathogenic variant, which is a founder mutation originated in the northwest of Spain. The aim of our study was to evaluate if these pts presented different outcomes when treated with first line platinum agents and iPARP.
Methods
We performed a single-centre retrospective analysis of pts carrying somatic and/or germline pathogenic variants of BRCA1 and BRCA2 treated with platinum agents and iPARP between January 2014 and June 2022. Variants were detected with validated methods in tissue and/or blood samples. Data was extracted from electronic health records and analysed with SPSS software.
Results
We found 36 pts with the aforementioned characteristics. Median age upon diagnosis was 56.2 (range 41 – 82) years. The initial FIGO stage was IIIC in 55.6% and IV in 33.3% of the cases. The majority of pts had an ECOG PS of 1 (58.3%) or 0 (33.3%). 26 pts (72.2%) had a BRCA1 variant, and of those 13 pts carried the BRCA1 c.211 A>G variant. These pts presented a worse objective response rate (ORR) to first line platinum-based chemotherapy when compared to all the pts (61.5% vs 87.0%, p = 0.04) and to BRCA1 mutated pts (61.5% vs 84.6%, p = 0.18). They also had a lower ORR to iPARP (15.4% vs 21.7%, p = 0.21). Median progression free survival (PFS) to first line treatment was lower among BRCA1 c.211 A>G variant carriers than the rest of the pts (28 vs 33 months, p= 0.41), as it was overall survival (OS) (72 vs 91 m, p = 0.29).
Conclusions
We found that pts with BRCA1 c.211 A>G germline pathogenic variant presented numerically worse outcomes when treated with DNA damaging agents, with a significantly lower ORR to platinum agents. Further research should be carried out to confirm if this mutation conveys less sensitivity to these therapies.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M.I. Gomez-Randulfe Rodriguez: Financial Interests, Personal, Stocks/Shares: PharmaMar, Eisai; Financial Interests, Personal, Invited Speaker: Merck, Bristol-Myers Squibb, Pfizer. M. Quindós: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Invited Speaker: GSK, Merck Sharp & Dohme, Roche, Bristol Myers Squibb. All other authors have declared no conflicts of interest.