Implications of metastatic stage at presentation in docetaxel naïve metastatic castrate resistant prostate cancer

Soumyajit Roy; Christopher J D Wallis; Scott C Morgan; Amar U Kishan; Amy Tu Trinh Le; Julia Malone; Yilun Sun; Daniel E Spratt; Fred Saad; Shawn Malone

doi:10.1002/pros.24512

Implications of metastatic stage at presentation in docetaxel naïve metastatic castrate resistant prostate cancer

Prostate. 2023 Jul;83(10):912-921. doi: 10.1002/pros.24512. Epub 2023 Apr 18.

Authors

Affiliations

¹ Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois, USA.
² Department of Urology, Mount Sinai Hospital and University Health Network, University of Toronto, Toronto, Ontario, Canada.
³ Division of Radiation Oncology, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, Ontario, Canada.
⁴ Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California, USA.
⁵ Rush Medical College, Chicago, Illinois, USA.
⁶ Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
⁷ Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ontario, USA.
⁸ Department of Radiation Oncology, University Hospital Seidman Cancer Center, Case Western Reserve University, Cleveland, Ontario, USA.
⁹ Department of Surgery, Université de Montréal, Montreal, Quebec, Canada.

PMID: 37071764
DOI: 10.1002/pros.24512

Abstract

Background: We performed a secondary analysis of ACIS study to determine if synchronous versus metachronous metastatic presentation has any association with survival and treatment response to dual androgen receptor axis-targeted therapy (ARAT) in docetaxel naïve metastatic castrate resistant prostate cancer (mCRPC).

Methodology: In this phase III randomized controlled trial, docetaxel naïve mCRPC patients were randomized to either apalutamide or placebo combined with abiraterone and prednisone. Multivariable Cox regression models were applied to determine the adjusted association of M-stage with radiographic progression-free survival (rPFS) and overall survival (OS). To determine the heterogeneity of treatment effect based on metastatic stage (M-stage) at presentation, Cox regression was applied with interaction terms between M-stage and treatment.

Results: Among 972 patients, 432 had M0, 334 had M1, while M-stage at presentation was unknown in 206. There was no association of M-stage at presentation with rPFS in patients with prior local therapy (LT) (hazard ratio for M1-stage: 1.22 [95% confidence interval: 0.82-1.82]; unknown: 1.03 [0.77-1.38]) or without prior LT (M1-stage: 0.87 [0.64-1.19]; unknown: 1.15 [0.77-1.72]) with no significant heterogeneity. Similarly, there was no association of M-stage with OS in patients with prior LT (M1-stage: 1.04 [0.81-1.33]; unknown: 0.98 [0.79-1.21]) or without prior LT (M1-stage: 0.95 [0.70-1.29]; unknown: 1.17 [0.80-1.71]) with no significant heterogeneity. Based on M-stage at presentation, we did not find any significant heterogeneity in treatment effect on rPFS (interaction p = 0.13), and OS (interaction p = 0.87).

Conclusion: M-stage at presentation had no association with survival in chemotherapy-naïve mCRPC. We did not find any statistically significant heterogeneity in efficacy of dual ARAT based on synchronous versus metachronous presentation.

Trial registration: ClinicalTrials.gov NCT02257736.

Keywords: androgen receptor axis targeted therapy; metachronous versus synchronous metastatic prostate cancer; metastatic castrate resistant prostate cancer.

Publication types

Randomized Controlled Trial
Clinical Trial, Phase III
Research Support, Non-U.S. Gov't

MeSH terms

Docetaxel / therapeutic use
Humans
Male
Prednisone / therapeutic use
Progression-Free Survival
Prostatic Neoplasms, Castration-Resistant* / drug therapy

Substances

Docetaxel
Prednisone

Associated data

ClinicalTrials.gov/NCT02257736