Therapeutic sensitivity to standard treatments in BRCA positive metastatic castration-resistant prostate cancer patients-a systematic review and meta-analysis.
Journal
Prostate cancer and prostatic diseases
ISSN: 1476-5608
Titre abrégé: Prostate Cancer Prostatic Dis
Pays: England
ID NLM: 9815755
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
06
09
2022
accepted:
29
11
2022
revised:
22
11
2022
medline:
13
11
2023
pubmed:
13
12
2022
entrez:
12
12
2022
Statut:
ppublish
Résumé
Recent oncology guidelines recommend BRCA1/2 testing for a wide range of prostate cancer (PCa) patients. In addition, PARP inhibitors are available for mutation-positive metastatic castration-resistant PCa (mCRPC) patients following prior treatment with abiraterone, enzalutamide or docetaxel. However, the question of which of these standard treatments is the most effective for BRCA1/2 positive mCRPC patients remains to be answered. The aim of this meta-analysis was to assess the efficacy of abiraterone, enzalutamide and docetaxel in BRCA1/2 mutation-positive mCRPC patients in terms of PSA-response (PSA50), progression-free survival (PFS) and overall survival (OS). As no interventional trials are available on this topic, we performed the data synthesis of BRCA1/2 positive mCRPC patients by using both proportional and individual patient data. For PSA50 evaluation, we pooled event rates with 95% confidence intervals (CI), while for time-to-event (PFS, OS) analyses we used individual patient data with random effect Cox regression calculations. Our meta-analysis included 16 eligible studies with 348 BRCA1/2 positive mCRPC patients. In the first treatment line, response rates for abiraterone, enzalutamide and docetaxel were 52% (CI: 25-79%), 64% (CI: 43-80%) and 55% (CI: 36-73%), respectively. Analyses of individual patient data revealed a PFS (HR: 0.47, CI: 0.26-0.83, p = 0.010) but no OS (HR: 1.41, CI: 0.82-2.42, p = 0.210) benefit for enzalutamide compared to abiraterone-treated patients. Our PSA50 analyses revealed that all the three first-line treatments have therapeutic effect in BRCA1/2 positive mCRPC; although, based on the results of PSA50 and PFS analyses, BRCA positive mCRPC patients might better respond to enzalutamide treatment. However, molecular marker-driven interventional studies directly comparing these agents are crucial for providing higher-level evidence.
Sections du résumé
BACKGROUND
BACKGROUND
Recent oncology guidelines recommend BRCA1/2 testing for a wide range of prostate cancer (PCa) patients. In addition, PARP inhibitors are available for mutation-positive metastatic castration-resistant PCa (mCRPC) patients following prior treatment with abiraterone, enzalutamide or docetaxel. However, the question of which of these standard treatments is the most effective for BRCA1/2 positive mCRPC patients remains to be answered. The aim of this meta-analysis was to assess the efficacy of abiraterone, enzalutamide and docetaxel in BRCA1/2 mutation-positive mCRPC patients in terms of PSA-response (PSA50), progression-free survival (PFS) and overall survival (OS).
METHODS
METHODS
As no interventional trials are available on this topic, we performed the data synthesis of BRCA1/2 positive mCRPC patients by using both proportional and individual patient data. For PSA50 evaluation, we pooled event rates with 95% confidence intervals (CI), while for time-to-event (PFS, OS) analyses we used individual patient data with random effect Cox regression calculations.
RESULTS
RESULTS
Our meta-analysis included 16 eligible studies with 348 BRCA1/2 positive mCRPC patients. In the first treatment line, response rates for abiraterone, enzalutamide and docetaxel were 52% (CI: 25-79%), 64% (CI: 43-80%) and 55% (CI: 36-73%), respectively. Analyses of individual patient data revealed a PFS (HR: 0.47, CI: 0.26-0.83, p = 0.010) but no OS (HR: 1.41, CI: 0.82-2.42, p = 0.210) benefit for enzalutamide compared to abiraterone-treated patients.
CONCLUSIONS
CONCLUSIONS
Our PSA50 analyses revealed that all the three first-line treatments have therapeutic effect in BRCA1/2 positive mCRPC; although, based on the results of PSA50 and PFS analyses, BRCA positive mCRPC patients might better respond to enzalutamide treatment. However, molecular marker-driven interventional studies directly comparing these agents are crucial for providing higher-level evidence.
Identifiants
pubmed: 36509931
doi: 10.1038/s41391-022-00626-2
pii: 10.1038/s41391-022-00626-2
pmc: PMC10638083
doi:
Substances chimiques
Docetaxel
15H5577CQD
enzalutamide
93T0T9GKNU
BRCA1 protein, human
0
BRCA1 Protein
0
BRCA2 protein, human
0
BRCA2 Protein
0
Nitriles
0
Types de publication
Meta-Analysis
Systematic Review
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
665-672Subventions
Organisme : Magyar Tudományos Akadémia (Hungarian Academy of Sciences)
ID : BO/00451/20/5
Informations de copyright
© 2022. The Author(s).
Références
Clin Cancer Res. 2021 Aug 15;27(16):4610-4623
pubmed: 34083234
Eur Urol. 2017 Jul;72(1):34-42
pubmed: 28259476
BMC Med Res Methodol. 2012 Feb 01;12:9
pubmed: 22297116
J Clin Oncol. 2015 Nov 20;33(33):3968-71
pubmed: 26392104
JCO Precis Oncol. 2019;3:
pubmed: 31131348
J Clin Oncol. 2019 Feb 20;37(6):490-503
pubmed: 30625039
Prostate. 2021 Dec;81(16):1382-1389
pubmed: 34516663
Prostate. 2019 Jun;79(8):880-895
pubmed: 30900310
Urol Oncol. 2021 Oct;39(10):729.e7-729.e16
pubmed: 33353867
Cancer Discov. 2013 Nov;3(11):1245-53
pubmed: 24027196
Int J Evid Based Healthc. 2015 Sep;13(3):147-53
pubmed: 26317388
N Engl J Med. 2020 May 28;382(22):2091-2102
pubmed: 32343890
Br J Cancer. 2011 Oct 11;105(8):1230-4
pubmed: 21952622
BMJ. 2011 Jul 22;343:d4002
pubmed: 21784880
BJU Int. 2012 Mar;109(5):713-9
pubmed: 21756279
J Clin Oncol. 2013 May 10;31(14):1748-57
pubmed: 23569316
J Clin Oncol. 2018 Apr 1;36(10):991-999
pubmed: 29261439
Eur Urol. 2018 Aug;74(2):218-225
pubmed: 29439820
Sci Rep. 2017 Jul 4;7(1):4574
pubmed: 28676659
Biochem Med (Zagreb). 2012;22(3):276-82
pubmed: 23092060
Eur Urol. 2018 May;73(5):687-693
pubmed: 29429804
Clin Cancer Res. 2021 Jul 1;27(13):3610-3619
pubmed: 33849963
BMC Med Inform Decis Mak. 2007 Jun 15;7:16
pubmed: 17573961
BMJ. 2021 Mar 29;372:n71
pubmed: 33782057
Cancer Discov. 2018 Apr;8(4):444-457
pubmed: 29367197
Lancet Oncol. 2019 Dec;20(12):1730-1739
pubmed: 31727538
Cancer. 2021 Jun 15;127(12):1965-1973
pubmed: 33690902
Prostate Cancer Prostatic Dis. 2022 Mar;25(1):71-78
pubmed: 34253846
J Natl Compr Canc Netw. 2021 May 14;19(8):905-914
pubmed: 33990090
JAMA Oncol. 2016 Dec 01;2(12):1598-1606
pubmed: 27148695
JCO Precis Oncol. 2020;4:355-366
pubmed: 32856010
Cancer Discov. 2013 Nov;3(11):1254-71
pubmed: 24027197
BMC Infect Dis. 2019 Nov 8;19(1):918
pubmed: 31699053
BJU Int. 2022 Mar;129(3):345-355
pubmed: 34185954