Pharmacologic synergy versus independent action in androgen receptor-axis-targeted agent-docetaxel triplet therapy for metastatic hormone-sensitive prostate cancer: a copula-based analysis.
[BACKGROUND] Triplet therapy combining androgen deprivation therapy (ADT), docetaxel, and androgen receptor-axis-targeted agents (ARATs) has exhibited survival benefits in metastatic hormone-sensitive
- 95% CI 0.93-1.44
APA
Chen W, Yoshida S, et al. (2026). Pharmacologic synergy versus independent action in androgen receptor-axis-targeted agent-docetaxel triplet therapy for metastatic hormone-sensitive prostate cancer: a copula-based analysis.. Urologic oncology, 44(4), 110990. https://doi.org/10.1016/j.urolonc.2025.110990
MLA
Chen W, et al.. "Pharmacologic synergy versus independent action in androgen receptor-axis-targeted agent-docetaxel triplet therapy for metastatic hormone-sensitive prostate cancer: a copula-based analysis.." Urologic oncology, vol. 44, no. 4, 2026, pp. 110990.
PMID
41570781
Abstract
[BACKGROUND] Triplet therapy combining androgen deprivation therapy (ADT), docetaxel, and androgen receptor-axis-targeted agents (ARATs) has exhibited survival benefits in metastatic hormone-sensitive prostate cancer (mHSPC). Whether these benefits originate from pharmacologic synergy or independent drug action (IDA) remains unclear.
[METHODS] Using reconstructed individual patient data from phase III trials, we applied a copula-based independent-action model to compare observed triplet outcomes with counterfactual predictions derived from docetaxel- and ARAT-based doublets. The primary analysis used weak positive dependence (θ = 0.24), with sensitivity analyses across a plausible range.
[RESULTS] The triplet, docetaxel-doublet, and ARAT-doublet cohorts comprised 138/355, 206/355, and 637/1,667 events/patients for rPFS, respectively. The observed triplet outcomes did not exceed independent-action predictions (observed/predicted Hazard ration [HR] 1.39; 95% Confidence Interval [95% CI] 1.12-1.74), with excellent concordance in curve shape (r = 0.99) and a difference of restricted mean survival time (ΔRMST) of 4.47 months favoring the prediction. Drug-matched analyses using abiraterone further reduced the discrepancy (HR 1.16; 95% CI 0.93-1.44; ΔRMST 2.93 months). Across the full plausible dependence range (θ = 0.08-0.40), findings remained consistent (HR 1.35-1.44). For overall survival, observed/predicted differences were larger (HR 1.87; 95% CI 1.61-2.17; r = 0.97; ΔRMST 7.59 months), but these results were considered exploratory due to substantial confounding from postprogression therapies.
[CONCLUSIONS] These findings did not identify any population-level benefit of triplet therapy that clearly exceeded predictions under an independent-action model, although synergistic effects at the individual-patient level cannot be excluded. These findings support selective or sequential treatment strategies to optimize the benefit-toxicity balance in appropriate patient populations.
[METHODS] Using reconstructed individual patient data from phase III trials, we applied a copula-based independent-action model to compare observed triplet outcomes with counterfactual predictions derived from docetaxel- and ARAT-based doublets. The primary analysis used weak positive dependence (θ = 0.24), with sensitivity analyses across a plausible range.
[RESULTS] The triplet, docetaxel-doublet, and ARAT-doublet cohorts comprised 138/355, 206/355, and 637/1,667 events/patients for rPFS, respectively. The observed triplet outcomes did not exceed independent-action predictions (observed/predicted Hazard ration [HR] 1.39; 95% Confidence Interval [95% CI] 1.12-1.74), with excellent concordance in curve shape (r = 0.99) and a difference of restricted mean survival time (ΔRMST) of 4.47 months favoring the prediction. Drug-matched analyses using abiraterone further reduced the discrepancy (HR 1.16; 95% CI 0.93-1.44; ΔRMST 2.93 months). Across the full plausible dependence range (θ = 0.08-0.40), findings remained consistent (HR 1.35-1.44). For overall survival, observed/predicted differences were larger (HR 1.87; 95% CI 1.61-2.17; r = 0.97; ΔRMST 7.59 months), but these results were considered exploratory due to substantial confounding from postprogression therapies.
[CONCLUSIONS] These findings did not identify any population-level benefit of triplet therapy that clearly exceeded predictions under an independent-action model, although synergistic effects at the individual-patient level cannot be excluded. These findings support selective or sequential treatment strategies to optimize the benefit-toxicity balance in appropriate patient populations.
MeSH Terms
Humans; Male; Docetaxel; Prostatic Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Receptors, Androgen; Drug Synergism; Androgen Antagonists; Neoplasm Metastasis; Taxoids; Aged
같은 제1저자의 인용 많은 논문 (5)
- FcγRIIb deficiency inhibits tumor development by attenuating the immunosuppressive phenotype of MDSCs.
- Effectiveness of KAP-based nursing program in managing digestive symptoms in colorectal cancer patients undergoing chemotherapy: A retrospective controlled study.
- Oligometastatic Prostate and Bladder Cancer: An Integrative Narrative Review.
- Real world deployment of a pancreatic cancer risk model: impact of refitting, imputation, and computational burden.
- IRF1 suppresses gastric tumorigenesis via dual PI3K/AKT-ERK pathway modulation and functional antagonism of oncogenic MX2.