Abstract
BackgroundPARP inhibitors (PARPi) have recently been approved for various malignancies based on the results of several clinical trials. However, these trials have mostly recruited patients with germline BRCA mutations, and it is unclear whether PARPi have similar efficacy in patients with somatic BRCA mutations. Our study aimed to determine the efficacy of PARPi in patients with somatic BRCA mutations.MethodsWe performed a meta-analysis comparing overall response rate to PARPi in patients harboring somatic versus germline BRCA mutations. We looked at studies including somatic and germline mutations in BRCA patients that received PARPi.ResultsAfter screening and removing duplicates, 18 studies met our criteria for including both somatic and germline BRCA mutations. Only 8 studies reported response rates for both somatic and germline BRCA mutations.In those studies, 24 out of 43 patients with somatic BRCA mutations (55.8%), and 69 out of 157 (43.9%) patients with germline BRCA patients had a response to therapy to PARPi. This difference was not statistically significant (p = 0.399).In all five studies that reported progression-free survival, there was no obvious difference in outcomes between somatic versus germline BRCA patients, however a precise statistical analysis could not be performed.ConclusionOur meta-analysis and systematic review of the literature indicates similar response rates of PARPi therapy in patients with somatic and germline BRCA mutations. Investigation of use of PARPi therapy in a broader patient population, and the inclusion of somatic BRCA mutations in further clinical trials is paramount in improving therapeutic options for our patients.
Highlights
Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) have recently been approved for various malignancies based on the results of several clinical trials
Characteristics of included studies Amongst the 18 studies that we identified that included both somatic and germline BRCA mutations treated with PARP inhibitors (PARPi), 14 studies involved use of PARPi as monotherapy, whereas 4 involved use of PARPi in combination with other therapies. 6 studies evaluated PARPi in a maintenance setting
Across all 18 studies, a total of 236 patients with somatic BRCA mutations were treated with PARPi, and 1204 patients with germline BRCA mutations were treated with PARPi
Summary
PARP inhibitors (PARPi) have recently been approved for various malignancies based on the results of several clinical trials. These trials have mostly recruited patients with germline BRCA mutations, and it is unclear whether PARPi have similar efficacy in patients with somatic BRCA mutations. Our study aimed to determine the efficacy of PARPi in patients with somatic BRCA mutations. Since their discovery in 1994 and 1995 respectively, there has been significant clinical interest in the tumor suppressor genes BRCA1 and BRCA2, with particular focus in recent years on targeted therapies for patients with BRCA mutated cancers. Somatic BRCA mutations which are present only in the tumor cells, have been reported to be up to 15–30% of all BRCA1/2 mutations, and can be found in various malignancies, such as 3% of breast cancer cases, and over 12% of advanced prostate cancer patients [6,7,8,9,10]
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