Effect of Concomitant Medications on Treatment Response and Survival in De Novo Metastatic Prostate Cancer: Secondary Analysis of the LATITUDE Study

Soumyajit Roy; Fred Saad; Christopher J D Wallis; Yilun Sun; Daniel E Spratt; Rishav Akilla; Amar U Kishan; Shawn Malone; Scott C Morgan

doi:10.1016/j.ejca.2023.113348

Effect of Concomitant Medications on Treatment Response and Survival in De Novo Metastatic Prostate Cancer: Secondary Analysis of the LATITUDE Study

Eur J Cancer. 2024 Mar:199:113348. doi: 10.1016/j.ejca.2023.113348. Epub 2023 Sep 20.

Authors

Soumyajit Roy¹, Fred Saad², Christopher J D Wallis³, Yilun Sun⁴, Daniel E Spratt⁵, Rishav Akilla⁶, Amar U Kishan⁷, Shawn Malone⁸, Scott C Morgan⁹

Affiliations

¹ Department of Radiation Oncology, Rush University Medical Center, Chicago, IL, USA. Electronic address: soumyajitroy8@gmail.com.
² Department of Surgery, Centre hospitalier de l'Université de Montréal, Montreal, QC, Canada.
³ Department of Urology, Mount Sinai Hospital, University Health Network, University of Toronto, Toronto, ON, Canada.
⁴ Case Western Reserve University, Cleveland, OH, USA.
⁵ Department of Radiation Oncology, University Hospitals, Seidman Cancer Center, Cleveland, OH, USA.
⁶ University of Houston, Houston, TX, USA.
⁷ Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA.
⁸ Department of Radiology, Radiation Oncology and Medical Physics, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, Canada.
⁹ Department of Radiology, Radiation Oncology and Medical Physics, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, Canada. Electronic address: smorgan@toh.ca.

PMID: 38262848
DOI: 10.1016/j.ejca.2023.113348

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.

MeSH terms

Abiraterone Acetate / therapeutic use
Androgen Antagonists / therapeutic use
Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Aspirin / therapeutic use
Humans
Male
Prostatic Neoplasms*
Prostatic Neoplasms, Castration-Resistant* / drug therapy

Substances

Androgen Antagonists
Abiraterone Acetate
Anti-Inflammatory Agents, Non-Steroidal
Aspirin