Related Experiment Video
Updated: Jun 26, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Comparative effectiveness of first-line systemic treatments for metastatic castration-resistant prostate cancer: a
Jiahuan Ai1, Liuying Jian1, Xiaoqin Wen1
1College of Pharmacy/Southern Institute of Pharmacoeconomics and Health Technology Assessment, Jinan University, Guangzhou, 510632, China.
Objectives:
No head-to-head trials had been performed to estimate the relative effectiveness of poly ADP-ribose polymerase inhibitor (PARPi) and androgen receptor signaling inhibitor (ARSi) in the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC). We aimed to perform a systematic review and network meta-analysis to evaluate the comparative effectiveness of various systemic treatment agents for patients with mCRPC.
Methods:
A comprehensive literature search was conducted for abstracts and full-text articles from the database's inception through April 27, 2023. The study concentrated on assessing radiographic progression-free survival (rPFS) for both overall and homologous recombination repair mutation (HRRm) population, with overall survival (OS) as the secondary measure. Under the Bayesian framework, the overall effect was pooled using the fixed-effects model in base case analysis. Scenario analysis using restricted mean survival time (RMST) methods was performed to test the robustness of the results.
Results:
Nine studies with 6,830 patients and 8 unique treatment options were included. Network meta-analysis demonstrated that talazoparib in combination with enzalutamide (TALA + ENZA; overall population, hazard ratio [HR], 0.20; 95% credible interval [CrI]: 0.16-0.26; RMST, 3.51; 95% confidence interval [CI] 2.46-4.60; HRRm population, HR, 0.15; 95% CrI: 0.09-0.23; RMST, 4.14; 95% CI 2.84-5.39) was superior to other treatments in the first-line setting in terms of rPFS. The results of Bayesian framework and RMST models showed consistent efficacy ranks. When extrapolated to overall survival benefit, within the Bayesian framework, olaparib plus abiraterone acetate and prednisone (OLAP + AAP) achieved the highest OS benefit for the overall population, which was not statistically significant when compared to TALA + ENZA. However, TALA + ENZA achieved the highest OS benefit at 3 years by applying RMST.
Conclusions:
We suggest that talazoparib in combination with enzalutamide is probably a preferred treatment agent for the overall population and HRRm patients with mCRPC. Given the limitations of network framework and the modeling assumptions undertaken to finalize the analyses, results should be cautiously interpreted.
Insights
Talazoparib plus enzalutamide shows superior radiographic progression-free survival in first-line metastatic castration-resistant prostate cancer. This combination may be a preferred treatment for both overall and HRRm populations.
Area of Science:
- Oncology
- Clinical Pharmacology
- Biostatistics
Background:
- Metastatic castration-resistant prostate cancer (mCRPC) lacks head-to-head trials comparing poly ADP-ribose polymerase inhibitors (PARPi) and androgen receptor signaling inhibitors (ARSi).
- Evaluating comparative effectiveness of first-line systemic treatments for mCRPC is crucial for optimizing patient outcomes.
Purpose of the Study:
- To conduct a systematic review and network meta-analysis.
- To evaluate and compare the effectiveness of various systemic treatment agents for mCRPC.
Main Methods:
- Comprehensive literature search up to April 2023.
- Network meta-analysis assessing radiographic progression-free survival (rPFS) and overall survival (OS).
- Bayesian framework with fixed-effects model and restricted mean survival time (RMST) analysis for robustness.
Main Results:
- Nine studies (6,830 patients) evaluated 8 treatment options.
- Talazoparib + enzalutamide (TALA + ENZA) demonstrated superior rPFS in overall and HRRm populations.
- Consistent efficacy ranks observed between Bayesian and RMST models; TALA + ENZA showed highest 3-year OS benefit by RMST.
Conclusions:
- Talazoparib + enzalutamide is a likely preferred first-line treatment for mCRPC patients, including HRRm.
- Results should be interpreted cautiously due to network meta-analysis limitations and modeling assumptions.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
01:20Comparing the Survival Analysis of Two or More Groups
01:21Cancer Survival Analysis