Therapeutic sensitivity to standard treatments in BRCA positive metastatic castration-resistant
prostate cancer patients — a systematic review and meta-analysis
(Open access funding provided by Semmelweis University)
Szakterületek:
Onkológia
Urológia és nefrológia
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
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
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
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.
