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

Előadó neve

Dr. Fazekas, Tamás

Előadó munkahelye

Semmelweis University Department of Urology

Előadó telefonszáma

06706118524

Előadó e-mail címe

fazekastamas192@gmail.com

Az előadás címe

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

Szerző(k) neve és munkahelye

Tamás Fazekas1,2, Adam Daniel Széles1,2, Anita Csizmarik1, Melinda Váradi1, Bálint Vékony1, Brigitta Teutsch2,4, Alex Váradi2,4, Tamás Kói2, Péter Hegyi2,4, Péter Nyirády1, Tibor Szarvas1,3
1 Department of Urology, Semmelweis University, Budapest, Hungary
2 Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
3 Department of Urology, University of Duisburg-Essen and German Cancer Consortium, Essen, Germany
4 Institute for Translational Medicine, University of Pécs, Medical School, Pécs, Hungary

Bemutatás módja

Szóbeli

Szekció

Clinical Medicine III.

Language of the presentation

English

Preferred session

Clinical Medicine

Összefoglaló szövege

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.

University and Doctoral School

Semmelweis University, Károly Rácz Doctoral School of Clinical Medicine

Supervisor

Prof. Tibor Szarvas

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6869

Start

15:15

End

15:30

Authors (legacy)

Tamás Fazekas1,2, Adam Daniel Széles1,2, Anita Csizmarik1, Melinda Váradi1, Bálint Vékony1, Brigitta Teutsch2,4, Alex Váradi2,4, Tamás Kói2, Péter Hegyi2,4, Péter Nyirády1, Tibor Szarvas1,3
1 Department of Urology, Semmelweis University, Budapest, Hungary
2 Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
3 Department of Urology, University of Duisburg-Essen and German Cancer Consortium, Essen, Germany
4 Institute for Translational Medicine, University of Pécs, Medical School, Pécs, Hungary