Effect of Concomitant Medications on Treatment Response and Survival in De Novo Metastatic Prostate Cancer: Secondary Analysis of the LATITUDE Study
Menée à partir de données portant sur 1 135 patients atteints d'un cancer métastatique de novo de la prostate, cette étude analyse l'impact, sur la survie globale et la mortalité spécifique, d'une utilisation de médicaments courants (metformine, statines, inhibiteurs de la pompe à protons, inhibiteurs de COX-2, aspirine, paracétamol, anti-inflammatoires non stéroïdiens) pendant un traitement anticancéreux (acétate d'abiratérone, prednisone, thérapie anti-androgénique)
Résumé en anglais
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, 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 effect from ADT plus abiraterone in de novo high risk mPCa based on receipt of concurrent medications. Receipt of NSAIDs was independently associated with increased PCSM and inferior OS.
