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.
BRCA
Germline
Meta-analysis
PARP inhibitors
Somatic
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
03 Jun 2020
03 Jun 2020
Historique:
received:
06
01
2020
accepted:
11
05
2020
entrez:
5
6
2020
pubmed:
5
6
2020
medline:
12
1
2021
Statut:
epublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 32493233
doi: 10.1186/s12885-020-06948-5
pii: 10.1186/s12885-020-06948-5
pmc: PMC7267765
doi:
Substances chimiques
BRCA1 Protein
0
BRCA1 protein, human
0
BRCA2 Protein
0
BRCA2 protein, human
0
Poly(ADP-ribose) Polymerase Inhibitors
0
Types de publication
Comparative Study
Journal Article
Meta-Analysis
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
507Références
Cancers (Basel). 2018 Dec 04;10(12):
pubmed: 30518089
JCO Precis Oncol. 2018;2018:
pubmed: 30051098
Eur J Epidemiol. 2010 Sep;25(9):603-5
pubmed: 20652370
Clin Cancer Res. 2014 Feb 1;20(3):764-75
pubmed: 24240112
Nature. 2005 Apr 14;434(7035):913-7
pubmed: 15829966
N Engl J Med. 2012 Apr 12;366(15):1382-92
pubmed: 22452356
J Clin Oncol. 2015 Jan 20;33(3):244-50
pubmed: 25366685
J Natl Cancer Inst. 1999 Aug 4;91(15):1310-6
pubmed: 10433620
N Engl J Med. 2015 Oct 29;373(18):1697-708
pubmed: 26510020
Eur Urol. 2019 Oct;76(4):452-458
pubmed: 30797618
Cancer. 2015 Jan 15;121(2):269-75
pubmed: 25224030
PLoS Med. 2009 Jul 21;6(7):e1000097
pubmed: 19621072
Lancet Oncol. 2019 May;20(5):636-648
pubmed: 30948273
Gynecol Oncol. 2015 May;137(2):343-50
pubmed: 25725131
Nature. 2011 Jun 29;474(7353):609-15
pubmed: 21720365
J Clin Oncol. 2010 Aug 1;28(22):3570-6
pubmed: 20606085
N Engl J Med. 2016 Dec;375(22):2154-2164
pubmed: 27717299
Nature. 2005 Apr 14;434(7035):917-21
pubmed: 15829967
JAMA. 2017 Jun 20;317(23):2402-2416
pubmed: 28632866
Lancet Oncol. 2019 Apr;20(4):570-580
pubmed: 30880072
Eur J Cancer. 2016 Jul;62:132-7
pubmed: 27189322
Nature. 2019 Jul;571(7766):576-579
pubmed: 31292550
Gynecol Oncol. 2017 Nov;147(2):267-275
pubmed: 28882436
N Engl J Med. 2019 Jul 25;381(4):317-327
pubmed: 31157963
Cancer Manag Res. 2019 May 10;11:4371-4390
pubmed: 31191001
N Engl J Med. 2017 Aug 10;377(6):523-533
pubmed: 28578601
Am J Hum Genet. 2016 May 5;98(5):818-829
pubmed: 27087322
Oncotarget. 2017 Jul 4;8(27):43653-43661
pubmed: 28525389
Nat Rev Cancer. 2011 Dec 23;12(1):68-78
pubmed: 22193408
Lancet Oncol. 2019 Oct;20(10):1409-1419
pubmed: 31474354
N Engl J Med. 2018 Aug 23;379(8):753-763
pubmed: 30110579
Ann Oncol. 2016 Aug;27(8):1532-8
pubmed: 27194814
Clin Cancer Res. 2017 Nov 1;23(21):6400-6410
pubmed: 28790114
Gynecol Oncol. 2019 Feb;152(2):270-277
pubmed: 30551885
BMJ. 2003 Sep 6;327(7414):557-60
pubmed: 12958120