Comparative Efficacy of First-Line (1L) Therapies for Patients With Asymptomatic/Mildly Symptomatic Metastatic Castration-Resistant Prostate Cancer (mCRPC): An Updated Systematic Literature Review (SLR) and Bayesian Network Meta-Analyses (NMAs)
Author(s)
Imtiaz Samjoo, MSc, PhD1, Stefanie Paganelli, BSc1, Jenna Ellis, MSc1, Anja Haltner, MSc2, Melissa Kirker, MPH, PharmD3, Neo Su, MPH, PharmD3, Jane Chang, MPH3, Elena Castro, MD, MSc, PhD4.
1EVERSANA, Burlington, ON, Canada, 2EVERSANA, New York, NY, USA, 3Pfizer, Inc., New York, NY, USA, 4Hospital Universitario 12 de Octubre, Madrid, Spain.
1EVERSANA, Burlington, ON, Canada, 2EVERSANA, New York, NY, USA, 3Pfizer, Inc., New York, NY, USA, 4Hospital Universitario 12 de Octubre, Madrid, Spain.
OBJECTIVES: Several therapies are available and used in clinical practice for 1L treatment of mCRPC. As mCRPC remains an area of active investigation, new trials have emerged and existing trials have reported more mature survival data. This study aimed to incorporate the latest evidence through NMAs to compare the efficacy of 1L treatments in an unselected mCRPC population, irrespective of gene status.
METHODS: A systematic literature review was updated from October 2022 through August 2024 using MEDLINE®, Embase, Cochrane via Ovid®, and key grey literature sources to identify relevant randomized controlled trials (RCTs). Bayesian random-effects NMAs were conducted for radiographic progress-free survival (rPFS) and overall survival (OS). Base case analyses excluded trials with clinical heterogeneity or violating proportional hazards assumptions. Sensitivity analyses assessed the impact of the base case. Treatments were ranked using surface under the cumulative ranking curves (SUCRAs), with higher values indicating greater likelihood of being effective.
RESULTS: Forty-two RCTs with published data were considered for NMAs. In the base case, the rPFS network included 16 RCTs and 17 treatments, while the OS network included 20 RCTs and 18 treatments. Talazoparib plus enzalutamide (TALA+ENZA) was the top-ranked treatment for rPFS (SUCRA: 89.6%) and OS (SUCRA: 84.4%). In sensitivity analyses, results for rPFS (15 RCTs; 16 treatments) remained consistent with the base case. In sensitivity analysis for OS (22 RCTs; 20 treatments), a non-standard docetaxel regimen, docetaxel 50 mg/m² plus prednisolone (DOC50+PL10; SUCRA: 89.9%), was the top-ranked treatment, followed by radium-223 plus enzalutamide (Ra55+ENZA; SUCRA: 87.7%), two treatments originally excluded from the base case.
CONCLUSIONS: This NMA provides a comprehensive indirect comparison of 1L treatments for mCRPC. TALA+ENZA ranked highest across all assessed outcomes in base case analyses and remained among the top treatments in sensitivity analyses. These findings can support evidence-based decision-making in selecting optimal 1L treatments for patients with mCRPC.
METHODS: A systematic literature review was updated from October 2022 through August 2024 using MEDLINE®, Embase, Cochrane via Ovid®, and key grey literature sources to identify relevant randomized controlled trials (RCTs). Bayesian random-effects NMAs were conducted for radiographic progress-free survival (rPFS) and overall survival (OS). Base case analyses excluded trials with clinical heterogeneity or violating proportional hazards assumptions. Sensitivity analyses assessed the impact of the base case. Treatments were ranked using surface under the cumulative ranking curves (SUCRAs), with higher values indicating greater likelihood of being effective.
RESULTS: Forty-two RCTs with published data were considered for NMAs. In the base case, the rPFS network included 16 RCTs and 17 treatments, while the OS network included 20 RCTs and 18 treatments. Talazoparib plus enzalutamide (TALA+ENZA) was the top-ranked treatment for rPFS (SUCRA: 89.6%) and OS (SUCRA: 84.4%). In sensitivity analyses, results for rPFS (15 RCTs; 16 treatments) remained consistent with the base case. In sensitivity analysis for OS (22 RCTs; 20 treatments), a non-standard docetaxel regimen, docetaxel 50 mg/m² plus prednisolone (DOC50+PL10; SUCRA: 89.9%), was the top-ranked treatment, followed by radium-223 plus enzalutamide (Ra55+ENZA; SUCRA: 87.7%), two treatments originally excluded from the base case.
CONCLUSIONS: This NMA provides a comprehensive indirect comparison of 1L treatments for mCRPC. TALA+ENZA ranked highest across all assessed outcomes in base case analyses and remained among the top treatments in sensitivity analyses. These findings can support evidence-based decision-making in selecting optimal 1L treatments for patients with mCRPC.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
CO57
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, Oncology