Similar response rates and survival with PARP inhibitors for patients with solid tumors harboring somatic versus Germline BRCA mutations: a Meta-analysis and systematic review

Abstract

Background: PARP 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. Methods: We 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. Results: After 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. Conclusion: Our 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.

The role of homologous recombination deficiency testing in ovarian cancer and its clinical implications: do we need it?

“…Somatic BRCA1/2 mutations are found in an additional 5%-7% of ovarian cancer 3 and have been described to be early events in carcinogenesis, based on retrospective analysis from Study19 showing that majority of cases had clonal, biallelic inactivation. 21 Across several phase III trials and meta-analyses, 22 somatic BRCA1/2 mutations have been associated with similar clinical outcomes compared with germline BRCA1/2 mutations. For example, on the ARIEL2 trial, response rates (74% and 85%, respectively) and PFS for patients with somatic and germline BRCA1/2 mutation were similar.…”

The Efficacy of Combined Cisplatin and Nanoparticle Albumin-Bound Paclitaxel in a Stage IV Pancreatic Squamous Cell Carcinoma Patient With a Somatic BRCA2 Mutation: A Case Report

“…Postoperatively, she received a regimen of olaparib combined with pembrolizumab after the liver lesion relapsed, and achieved an SD, which suggests a potential efficacy of PARP inhibitors in somatic BRAC1/2 mutant pancreatic SCC. Although olaparib is only approved for pancreatic adenocarcinoma with germline BRCA1/2 mutation, the latest study showed comparable response rates and survivals with PARP inhibitors for patients harboring somatic versus germline BRCA mutations ( 16 ). Our study also provides preliminary evidence for extending the indication to the somatic BRAC1/2 mutant setting.…”

Poly(ADP-Ribose) Polymerase Inhibitors in Prostate Cancer: Molecular Mechanisms, and Preclinical and Clinical Data

“…It is not yet clear which patients achieve the greatest benefit. The meta-analysis by Mohyuddin et al indicates that the response rates and survival for patients with somatic and germline mutations are similar [ 93 ]. There is a suggestion that patients with biallelic BRCA2 inactivation achieved the greatest benefit in comparison to non-BRCA mutated patients.…”