PhD Scientific Days 2023

Budapest, 22-23 June 2023

Clinical Medicine - Posters I

PARP inhibitor’s efficacy is comparable to platinum chemotherapy in BRCA1/2 positive metastatic castration-resistant prostate cancer – a systematic review and meta-analysis

Tamás Fazekas1,2, Ádám D. Széles1,2, Brigitta Teutsch2,3, Anita Csizmarik1, Bálint Vékony1, Tamás Kói2,4, Zsolt Lang2,5, Nándor Ács2,6, Péter Hegyi2,3,7, Boris Hadaschik8, Péter Nyirády1,2, Tibor Szarvas1,8

1. Department of Urology, Semmelweis University, Budapest, Hungary
2. Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
3. Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
4. Department of Stochastics, Institute of Mathematics, Budapest University of Technology and Economics, Budapest, Hungary
5. Department of Biostatistics, University of Veterinary Medicine Budapest, Budapest, Hungary
6. Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary
7. Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
8. Department of Urology, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany

Text of the abstract

Introduction: The evolution of treatment landscape of metastatic castration-resistant prostate cancer (mCRPC) raised the need for biomarkers, to optimise treatment planning. BRCA1/2 testing has emerged as a novel decision-making tool in the hand of the clinician. Patients with mCRPC harbouring BRCA1/2 mutations are known to be more sensitive to both PARP inhibitor (PARPi) and platinum treatments, while the impact of the mutation to cabazitaxel and PSMA-ligand therapy is currently unknown.
Aims: The aim of this meta-analysis was to assess the efficacy of second- or later-line therapies in BRCA1/2 mutation-positive mCRPC patients in terms of PSA-response (PSA50), progression-free (PFS) and overall survival (OS).
Materials and Methods: For PSA50 evaluation, we pooled event rates with 95% confidence intervals (CI), while for time-to-event (PFS, OS) analyses we used random effect Cox regression calculations and median pooling.
Results: PSA50 response rates for PARPi and platinum were 69% (CI: 53-82%) and 74% (CI: 49-90%) respectively. Moreover, individual patient level data showed no OS difference between PARPi and platinum treatments (HR: 0.86; CI: 0.49−1.52; p=0.60). Median pooling of different PARPi compounds revealed similar PFS (9.7 months, CI: 8.12-12.55; I2: 37.49%) and OS (17.4 months, CI: 12.73-20.19; I2: 36.35%).
Conclusions: We showed that different PARP inhibitors have similar efficacy in terms of PFS and OS. Moreover, PARPi and platinum therapies were comparable regarding their PSA50 response rates and OS, highlighting that platinum is a valid treatment option for BRCA1/2 positive mCRPC patients. Prospective, molecular marker-driven interventional studies comparing these agents are crucial for providing higher-level evidence.
Funding: Tibor Szarvas. was supported by a János Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00451/20/5). This work was supported by the ÚNKP-21-5-SE-3, ÚNKP-21-3-II-SE-13, ÚNKP-22-3-1-SE-19 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund.