We performed an exploratory analysis of the SPARTAN trial to determine whether concomitant exposure to several classes of commonly prescribed medications influenced the effect of apalutamide on overall survival (OS) and metastasis-free survival (MFS) in patients with non-metastatic castration-resistant prostate cancer (nmCRPC).
SPARTAN was a phase III randomized controlled trial in which nmCRPC patients were randomly assigned in a 2:1 ratio to receive androgen deprivation therapy with or without apalutamide. We focused on 5 commonly prescribed classes of medications: metformin, statins, angiotensin converting enzyme inhibitors (ACEI), acetylsalicylic acid (ASA), and proton pump inhibitors (PPI) based on a plausible biological and clinical rationale. To determine the potential effect modification, we applied multivariable Cox regression models for OS and MFS separately with additional interaction terms. To determine the independent association of concomitant medications with OS and MFS, we used IPTW-based log-rank test. A 2-sided p < 0.01 was considered statistically significant.
We did not find statistically significant differences in effect from apalutamide on OS across subgroups stratified by concomitant exposure to any of the medication classes. While there was some difference in the treatment effect from apalutamide on MFS between patients with concomitant statins (adjusted hazard ratio [aHR]: 0.20; 95 % CI: 0.15-0.28) versus without concomitant statins (aHR: 0.31 [0.24-0.39]), this did not reach the pre-specified threshold of statistical significance (p = 0.011). On IPTW-based analysis, patients treated concomitantly with metformin (median: not reached versus 31 months; p = 0.002), or ACEI (median: 37 versus 29 months, p = 0.006) had significantly improved MFS.
In this post-hoc exploratory analysis of SPARTAN, effects of apalutamide on MFS and OS were consistent across subgroups stratified by exposure to concomitant medications. Exposure to concomitant metformin and ACEI was independently associated with a significant improvement in MFS.
European journal of cancer (Oxford, England : 1990). 2024 Jun 27 [Epub ahead of print]
Soumyajit Roy, Fred Saad, Yilun Sun, Shawn Malone, Daniel E Spratt, Amar U Kishan, Christopher J D Wallis, Angela Y Jia, Osama Mohamad, Umang Swami, Michael Ong, Neeraj Agarwal, Simon Chowdhury, Scott C Morgan
Department of Radiation Oncology, Rush University Medical Center, Chicago, IL, USA. Electronic address: ., Department of Surgery, Centre hospitalier de l'Université de Montréal, Montréal, QC, Canada., Case Western Reserve University, Cleveland, OH, USA., Department of Radiology, Radiation Oncology and Medical Physics, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, Canada., Department of Radiation Oncology, University Hospitals, Seidman Cancer Center, Cleveland, OH, USA., Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA., Department of Urology, Mount Sinai Hospital, University Health Network, University of Toronto, Toronto, ON, Canada., Division of Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA., Department of Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA., Division of Medical Oncology, Department of Medicine, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, Canada., Guy's and St Thomas' NHS Foundation Trust and Sarah Cannon Research Institute, London, UK., Department of Radiology, Radiation Oncology and Medical Physics, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, Canada. Electronic address: .