Saturday, June 15, 2024

Comparative Effectiveness of First-Line Treatments for Metastatic Castration-Resistant Prostate Cancer

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Emerging treatments for metastatic castration-resistant prostate cancer (mCRPC) necessitate a thorough evaluation of their comparative effectiveness. This study delves into the relative efficacy of poly ADP-ribose polymerase inhibitors (PARPi) versus androgen receptor signaling inhibitors (ARSi) as first-line treatments. By leveraging a network meta-analysis under a Bayesian framework, researchers aim to guide clinical decisions with robust data on radiographic progression-free survival (rPFS) and overall survival (OS) outcomes.

Study Methods and Population

A comprehensive literature review was completed, encompassing databases from their inception until April 27, 2023. The primary focus was on assessing rPFS for both the overall and homologous recombination repair mutation (HRRm) populations, with OS as a secondary measure. The analysis employed a fixed-effects model as its base case, further validated through scenario analysis using restricted mean survival time (RMST) methods.

The study included nine trials involving 6,830 patients and eight distinct treatment regimens. This rigorous approach ensures a broad yet detailed perspective on treatment efficacies across different patient subsets.

Key Findings and Efficacy Rankings

Results from the network meta-analysis revealed that the combination of talazoparib and enzalutamide (TALA + ENZA) outperformed other treatments in terms of rPFS. Specifically, for the overall population, the hazard ratio (HR) was 0.20, with a 95% credible interval (CrI) of 0.16-0.26, and an RMST of 3.51. For HRRm patients, the HR was 0.15, with a 95% CrI of 0.09-0.23, and an RMST of 4.14. These results were consistent across both Bayesian and RMST models, affirming the robustness of the findings.

When considering OS benefits, olaparib combined with abiraterone acetate and prednisone (OLAP + AAP) indicated the highest benefit for the overall population. However, the statistical significance was not distinct when compared to TALA + ENZA. Interestingly, TALA + ENZA showed the most substantial OS benefit over a 3-year period when evaluated through RMST.

User-Usable Inferences

– Talazoparib and enzalutamide combination shows superior rPFS in both overall and HRRm populations.
– The OLAP + AAP regimen offers notable OS benefits but is comparable to TALA + ENZA.
– RMST methods confirmed the consistency of efficacy rankings over a 3-year period.
– The Bayesian framework ensures robust comparative effectiveness despite the inherent limitations of network meta-analysis.

The study concludes that talazoparib in combination with enzalutamide is likely the preferred first-line treatment for both the overall and HRRm populations with mCRPC. Nevertheless, given the limitations of the network framework and the modeling assumptions, the results warrant cautious interpretation.

Original Article: Clin Transl Oncol. 2024 May 15. doi: 10.1007/s12094-024-03506-4. Online ahead of print.

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