Effect of concomitant medications on treatment response and survival in non-metastatic castrate resistant prostate cancer: Exploratory analysis of the SPARTAN trial.
Eur J Cancer
; 211: 114197, 2024 Jun 27.
Article
en En
| MEDLINE
| ID: mdl-39243730
ABSTRACT
BACKGROUND:
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). PATIENTS ANDMETHODS:
SPARTAN was a phase III randomized controlled trial in which nmCRPC patients were randomly assigned in a 21 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.RESULTS:
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.CONCLUSIONS:
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.
Texto completo:
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Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Eur J Cancer
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Reino Unido