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Updated: Jul 16, 2025
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Poly (ADP-ribose) Polymerase Inhibitors Have Comparable Efficacy with Platinum Chemotherapy in Patients with
Tamás Fazekas1, Ádám D Széles1, Brigitta Teutsch2
1Department of Urology, Semmelweis University, Budapest, Hungary; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary.
Context:
Testing for mutations in Breast Cancer Gene 1/2 (BRCA) has emerged as a novel decision-making tool for clinicians. Patients with metastatic castration-resistant prostate cancer (mCRPC) harboring pathogenic BRCA mutations can benefit from poly (ADP-ribose) polymerase inhibitor (PARPi) and platinum treatments, whereas the impact of the mutation on sensitivity to cabazitaxel and prostate-specific membrane antigen (PSMA)-ligand therapy is currently unknown.
Objective:
To assess the efficacy of PARPi, platinum, cabazitaxel, and PSMA-ligand therapies in BRCA-positive mCRPC.
Evidence Acquisition:
Databases were queried in February 2022. We performed data synthesis by using both proportional and individual patient data. For prostate-specific antigen (PSA) response rate (≥50% decrease from baseline [PSA50]) evaluation, we pooled event rates with 95% confidence intervals (CIs). Progression-free (PFS) and overall (OS) survival analyses with individual patient data were performed with the mixed-effect Cox proportional hazard model and single-arm random-effect analysis, providing pooled medians.
Evidence Synthesis:
We included 23 eligible studies with 901 BRCA-positive mCRPC patients. PSA50 response rates for PARPi and platinum were 69% (CI: 53-82%), and 74% (CI: 49-90%), respectively. Analyses of OS data showed no difference between PARPi and platinum treatments (hazard ratio: 0.86; CI: 0.49-1.52; p = 0.6). The single-arm OS and PFS analyses revealed similarities among different PARPis; pooled PFS and OS medians were 9.7 mo (CI: 8.1-12.5) and 17.4 mo (CI: 12.7-20.1), respectively.
Conclusions:
Our data revealed that different PARPis were similarly effective in terms of PFS and OS. Moreover, we found that PARPi and platinum therapy were comparable in terms of PSA50 response rate and OS, highlighting that platinum is a valid treatment option for BRCA-positive mCRPC patients. However, prospective interventional studies comparing these agents are essential to provide a higher level of evidence.
Patient Summary:
In this report, we found that different poly (ADP-ribose) polymerase inhibitors had similar efficacy, and platinum was a valid treatment option in BRCA-positive metastatic castration-resistant prostate cancer patients.
Insights
Poly (ADP-ribose) polymerase inhibitors (PARPi) show similar efficacy in BRCA-positive metastatic castration-resistant prostate cancer (mCRPC). Platinum therapy is also a viable option, comparable to PARPi in response rates and overall survival for mCRPC patients.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- BRCA mutations are key biomarkers in metastatic castration-resistant prostate cancer (mCRPC).
- Poly (ADP-ribose) polymerase inhibitors (PARPi) and platinum treatments show promise for BRCA-mutated mCRPC.
- The efficacy of cabazitaxel and PSMA-ligand therapy in this context is under investigation.
Purpose of the Study:
- To evaluate the effectiveness of PARPi, platinum, cabazitaxel, and PSMA-ligand therapies in patients with BRCA-positive mCRPC.
- To compare treatment outcomes for different therapeutic strategies in this patient cohort.
Main Methods:
- Systematic literature review and data synthesis of 23 studies involving 901 BRCA-positive mCRPC patients.
- Analysis of prostate-specific antigen response rate (PSA50) using pooled event rates.
- Progression-free survival (PFS) and overall survival (OS) analyses utilizing individual patient data and mixed-effect Cox models.
Main Results:
- PARPi and platinum therapies demonstrated comparable PSA50 response rates (69% and 74%, respectively).
- No significant difference in overall survival (OS) was observed between PARPi and platinum treatments.
- Median PFS and OS for PARPi were 9.7 and 17.4 months, respectively, with similar efficacy across different PARPi agents.
Conclusions:
- Different PARPis exhibit similar efficacy in terms of PFS and OS for BRCA-positive mCRPC.
- Platinum therapy is a valid and comparable treatment option to PARPi for BRCA-positive mCRPC.
- Further prospective studies are required to establish definitive evidence for treatment comparisons.
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