Age-related efficacy and safety of apalutamide (APA) plus ongoing androgen deprivation therapy (ADT) in subgroups of patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC): Post hoc analysis of SPARTAN.

Abstract

5024 Background: SPARTAN, a randomized phase 3 placebo (PBO)-controlled study in pts with high-risk nmCRPC and PSA doubling time ≤ 10 mo, showed that, compared with PBO, addition of APA to ongoing ADT treatment (tx) prolonged metastasis-free survival (MFS) by > 2 y, reduced the risk of symptomatic progression by 55%, and increased second progression-free survival (PFS2), which is the time from randomization to disease progression on first subsequent anticancer tx, or death. The impact of APA in terms of benefit and safety profile was evaluated in pts aged < 65, 65-74, and ≥ 75 y. Methods: Pts with nmCRPC were randomized 2:1 to APA (240 mg QD) or PBO; ADT was continuous. APA effect was analyzed by Cox models and Kaplan-Meier methods across age subgroups. Results: Baseline characteristics among age groups were similar, although ECOG PS 1 vs 0 increased with age. MFS benefit with APA was highly significant for all age subgroups (Table). In pts ≥ 75 y, MFS risk with APA vs PBO was reduced by 59%; MFS risk was reduced by 86% and 76% for pts < 65 and 65-74 y, respectively. Risk of PFS2 with APA vs PBO was reduced across all age subgroups. PFS2 in pts < 65, 65-74, and ≥ 75 y: HR, 0.09 (p < 0.0001); HR, 0.56 (p = 0.0343); HR, 0.59 (p = 0.0092), respectively. Risk of symptomatic progression was lessened with APA vs PBO for all age subgroups (Table). There was a similar increase in incidence of tx-emergent adverse events (TEAE) with age in both tx arms that remained higher with APA. Incidence of grade 3/4 TEAE (≥ 75 vs < 65 y): APA, 50% vs 37%; PBO, 37% vs 28%. Conclusions: Pts in all age subgroups with high-risk nmCRPC had significant improvement in MFS with APA + ongoing ADT. The safety profile of APA was similar across age subgroups. Clinical trial information: NCT01946204. [Table: see text]