Evaluation of concomitant medications in advanced prostate cancer patients receiving apalutamide: TITAN and SPARTAN post-hoc analysis.

Abstract

5087 Background: Apalutamide (APA) is an androgen receptor pathway inhibitor (ARPI) approved for use with androgen-deprivation therapy (ADT) in patients with metastatic castration-sensitive prostate cancer and nonmetastatic castration-resistant prostate cancer based on data from the phase 3 TITAN and SPARTAN trials. APA induces cytochrome (CYP) 3A4/2C19 and P-glycoprotein, which may alter the pharmacokinetics of commonly used medications, raising the possibility for adverse events (AEs) or serious adverse events (SAEs) due to drug-drug interactions (DDIs). Methods: A post-hoc analysis was conducted to evaluate the incidence of AEs associated with select concomitant medication classes—antihypertensives, antidiabetics, statins, proton pump inhibitors (PPIs), and corticosteroids, among patients treated with APA + ADT or placebo + ADT in the TITAN and SPARTAN trials. The selected drug classes include some of the most frequently prescribed agents with significant CYP 3A4/2C19 activities. This analysis was also done in comparison to non-recipients of concomitant medications. Results: See Table. Conclusions: In this exploratory post-hoc analysis of >2,200 patients from TITAN and SPARTAN, concomitant use of commonly prescribed medications (antihypertensives, antidiabetics, statins, PPIs, and corticosteroids) was frequent and reflected routine real-world practice. Across medication classes, we observed no clinically meaningful increase in serious or loss-of-efficacy adverse events among apalutamide-treated recipients compared with placebo or with non-recipients of the class. These findings suggest that co-administration of apalutamide with routine concomitant therapies is safe and feasible under standard clinical monitoring. Clinical trial information: NCT02489318 and NCT01946204 . Incidence of side effects for selected classes of concomitant medications by study and treatment actually received. Medication Class Treatment TITANRecipients(%) TITANTEAS(%) TITANTE SAEs(%) SPARTANRecipients(%) SPARTANTEAEs(%) SPARTANTE SAEs(%) Antihypertensives APA+ADT (PBO+ADT) 41 (34.3) 41.9 (39.2) 1.9 (1.7) 42.8 (41) 49.4 (36.8) 0.9 (0.6) Antidiabetics APA+ADT (PBO+ADT) 12.2 (10.8) 34.4 (33.3) 1.6 (1.8) 12.2 (9.3) 42.9 (27) 3.1 (0) Statins APA+ADT (PBO+ADT) 23.9 (15.6) 12 (11) 0 (0) 33.9 (31.7) 10.7 (6.3) 0 (0) PPIs APA+ADT (PBO+ADT) 17.6 (14.6) 6.5 (1.3) 0 (0) 26 (21.6) 8.6 (9.3) 0 (1.2) Corticosteroids APA+ADT (PBO+ADT) 14.9 (11.2) 12.8 (18.6) 1.3 (0) 10.7 (8.3) 18.6 (15.2) 1.2 (0) Treatment-emergent AEs (TEAEs) and SAEs deemed attributable to the pharmacologic class of the concomitant medication are classified as class-related side effects and included in the analysis. Percentages of TEAEs and SAEs are calculated based on recipients of a given class of concomitant medication.