Effect of Concomitant Medications on Treatment Response and Survival in De Novo Metastatic Prostate Cancer: Secondary Analysis of the LATITUDE Study - PubMed (original) (raw)
Effect of Concomitant Medications on Treatment Response and Survival in De Novo Metastatic Prostate Cancer: Secondary Analysis of the LATITUDE Study
Soumyajit Roy et al. Eur J Cancer. 2024 Mar.
Abstract
Purpose: It is unclear whether exposure to commonly prescribed medications influences survival and treatment response in patients with de novo high-risk metastatic prostate cancer (mPCa) treated with androgen receptor pathway inhibitors (ARPIs).
Methods: We performed a secondary analysis of the LATITUDE trial to determine whether receipt of concomitant medications influenced the effect of abiraterone acetate and prednisone, in addition to androgen deprivation therapy (ADT), on overall survival (OS) and prostate cancer-specific mortality (PCSM) in patients with de novo mPCa. We focused on 7 commonly prescribed classes of medications: metformin, statins, proton pump inhibitors (PPIs), cyclooxygenase 2 (COX-2) inhibitors, aspirin, acetaminophen, and NSAIDs (nonselective COX inhibitors). To account for multiple testing, a two-sided p < 0.0024 was set as the threshold for statistical significance.
Results: Overall, 1135 patients were eligible. There was some evidence of a differential treatment effect from abiraterone among patients who received concomitant NSAIDs (hazard ratio [HR] for OS: 0.54; 95% CI: 0.42-0.70) versus those who did not (HR: 0.74; 95% CI: 0.60-0.91), though this did not reach significance (interaction p = 0.05). A similar non-significant finding of heterogeneity of effect from abiraterone was noted among patients who received concomitant aspirin (HR for OS: 0.93 [0.63-1.36]) versus those who did not (HR: 0.61 [0.51-0.73]) (interaction p = 0.04). Receipt of NSAIDs was independently associated with a significantly inferior OS (HR: 1.37 [1.15-1.62]; p < 0.001) and higher relative incidence of PCSM (sHR: 1.47 [1.21-1.78]; p < 0.001).
Conclusions: This exploratory analysis did not find statistically significant evidence of differences in treatment effects from ADT plus abiraterone in de novo high-risk mPCa based on the receipt of concurrent medications. The receipt of NSAIDs was independently associated with increased PCSM and inferior OS.
Keywords: Abiraterone; Concomitant medications; Metastatic hormone sensitive prostate cancer; Metformin; Statins.
Copyright © 2023 Elsevier Ltd. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest Outside of this work, Dr. Roy reports research grant from Swim Across America. Dr. Spratt reports personal fees from Blue Earth, personal fees from Janssen, personal fees from AstraZeneca, Gammatile, Varian, and Boston Scientific, outside the submitted work. Outside of this work, Dr. Morgan reports personal fees from Astellas, Bayer, Janssen, and TerSera. Dr. Saad reports grants, personal fees, and non-financial support from Janssen, during the conduct of the study; grants, personal fees, and non-financial support from Astellas, grants, personal fees, and non-financial support from Bayer, outside the submitted work. Dr. Wallis has received honoraria from Bayer, EMD Serono, Knight Therapeutics, Haymarket Media, Science & Medicine Canada, TerSera Canada, and Tolmar Pharmaceuticals Canada; reports consulting fees from Janssen Oncology SESEN Bio, and Precision Point Specialty LLC; and has received research funding from Knight Therapeutics outside the submitted work. Dr. Malone has received honoraria from Astellas, Bayer, Janssen, and Sanofi; and travel and accommodations support from TerSera and Sanofi. There are no other conflicts of interest among the other authors.
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