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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
Mohyuddin, Ghulam Rehman Aziz, Muhammad Britt, Alec Wade, Lee Sun, Weijing Baranda, Joaquina Al-Rajabi, Raed Saeed, Anwaar Kasi, Anup
Mohyuddin, Ghulam Rehman
Aziz, Muhammad
Britt, Alec
Wade, Lee
Sun, Weijing
Baranda, Joaquina
Al-Rajabi, Raed
Saeed, Anwaar
Kasi, Anup
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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.
Description
A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.
Date
2020-06-03
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BioMed Central
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Keywords
PARP inhibitors, BRCA, Somatic, Germline, Meta-analysis
Citation
Mohyuddin, G.R., Aziz, M., Britt, A. et al. 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. BMC Cancer 20, 507 (2020). https://doi.org/10.1186/s12885-020-06948-5