PhD Scientific Days 2022

Clinical Medicine III.

Different Response to Standard First-line Treatments in BRCA Positive Metastatic Castration-resistant Prostate Cancer Patients – a Systematic Review and Meta-analysis

Text of the abstract

Introduction: Recent development of molecular oncology directed a special focus on BRCA1/2 mutation positive prostate cancers (PCa). Based on literature data, BRCA positive PCa-s are diagnosed at younger age and are associated with a more aggressive clinical behavior. Recent oncology guidelines recommend BRCA testing for PCa patients with positive family history, high-risk localized or metastatic disease. In addition, PARP inhibitors are available for metastatic castration-resistant PCa (mCRPC) from the second treatment line for mutation positive patients. However, the question of which first-line treatment is the most effective for BRCA positive mCRPC patients remains unclear.
Aim: The aim of this meta-analysis was to assess the efficacy of abiraterone, enzalutamide and docetaxel in BRCA 1 and 2 mutation positive mCRPC patients in terms of PSA-response (PSA50) progression-free survival (PFS) and overall survival (OS).
Methods: Considering that no intervention trials are available in the topic, we performed a proportional and an individual patient data meta-analysis (PROSPERO no.: CRD42021285267). For PSA50, we pooled event rates with 95% confidence intervals, in case of time to event data we compared different agents based on individual patient data using the random effect Cox regression with HR-s and 95% CI calculation. Heterogeneity was tested with I² test. Based on the heterogeneity of the studies we used random-effect model with the DerSimonian-Laird method.
Results: Our meta-analysis, included 16 eligible studies with an overall number of 348 BRCA positive patients. In the first treatment line, response rates were 52% (CI: 25-79%; I2: 57%), 64% (CI: 43-80%; I2: 0%) and 55% (CI: 36-73%; I2: 1%) for abiraterone, enzalutamide and docetaxel, respectively. Calculations performed on individual patient data revealed a PFS benefit for enzalutamide compared to abiraterone-treated patients (HR: 0.47, CI: 0.26-0.83, p=0.009). Regarding OS, our results showed no difference between these two agents (HR: 1.41, CI: 0.82-2.42, p=0.21).
Conclusions: Based on the results of PSA50 and individual patient data analysis of PFS, BRCA positive mCRPC patients might benefit most from enzalutamide treatment. However, molecular marker-driven interventional studies comparing directly these agents are crucial to provide higher evidence.