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Heterogeneity in Treatment Effects of Reduced Versus Standard Dose of Cabazitaxel in Metastatic Castration‐Resistant Prostate Cancer
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Heterogeneity in Treatment Effects of Reduced Versus Standard Dose of Cabazitaxel in Metastatic Castration‐Resistant Prostate Cancer
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Heterogeneity in Treatment Effects of Reduced Versus Standard Dose of Cabazitaxel in Metastatic Castration‐Resistant Prostate Cancer
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Journal Article
Heterogeneity in Treatment Effects of Reduced Versus Standard Dose of Cabazitaxel in Metastatic Castration‐Resistant Prostate Cancer
2026
Overview
Background In the PROSELICA, a randomized controlled trial (RCT) comparing cabazitaxel 20 mg/m2 (C20) versus 25 mg/m2 (C25) in metastatic castration‐resistant prostate cancer (mCRPC), one‐variable‐at‐a‐time subgroup analysis suggested possible heterogeneity in treatment effect (HTE) of C25 versus C20 among study participants. Novel predictive HTE analysis approaches may provide an in‐depth understanding of such results. Methods We analyzed patient‐level data from 1200 patients with mCRPC who were randomized in the PROSELICA trial. Outcomes included overall survival (OS) and progression‐free survival (PFS). Using baseline characteristics, patients were stratified into quartiles based on either quantitative baseline risk of poor outcome (risk modeling) or predicted individualized treatment effect (ITE) using a causal survival forest algorithm (effect modeling). Treatment effects were measured as differences in restricted mean survival time (RMST). Results For risk modeling, the OS effect of C25 increased with risk quartiles: −0.07 months (95% CI, −1.60 to 1.46) in the lowest risk quartile and 1.67 months (95% CI, 0.25 to 3.10) in the highest risk quartile. For effect modeling, the OS effect ranged from −0.17 months (95% CI, −3.01 to 2.68) in the lowest ITE quartile to 0.57 months (95% CI, −2.27 to 3.41) in the highest ITE quartile. Both approaches demonstrated greater C25 benefit in patients with extensive previous treatment and baseline disease burden. PFS effects remained consistent across all quartiles. Conclusions The OS effect of C25 versus C20 may vary based on baseline characteristics in post‐docetaxel mCRPC. Patients with extensive treatment history and disease burden may benefit more from C25.
Publisher
John Wiley & Sons, Inc,Wiley
Subject
/ Antineoplastic Agents - administration & dosage
/ heterogeneous treatment effect
/ Humans
/ Male
/ metastatic castration‐resistant prostate cancer
/ Patients
/ Prostatic Neoplasms, Castration-Resistant - drug therapy
/ Prostatic Neoplasms, Castration-Resistant - mortality
/ Prostatic Neoplasms, Castration-Resistant - pathology
/ Survival
