Relationship of time to metastasis (TTM) and site of metastases in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC): Results from the phase 3 SPARTAN trial.

5033 Background: SPARTAN, a randomized placebo (PBO)-controlled phase 3 study, evaluated the effect of apalutamide (APA), an orally administered next-generation androgen receptor inhibitor, in men with nmCRPC and a rapidly rising PSA. In SPARTAN, APA was associated with a 73% relative risk reduction of distant metastasis. We assessed the relationship between TTM and site of metastases after androgen deprivation therapy (ADT) plus APA or PBO. Methods: 1207 pts with nmCRPC and PSA doubling time (PSADT) ≤ 10 months were randomized 2:1 to APA (240 mg QD) or PBO, with concurrent ADT (both arms). TTM, defined as time from randomization to first evidence of blinded central review–confirmed radiographically detectable distant metastasis, was assessed by site of metastases, nodal (M1 nodes + soft tissue) vs bone (bone ± M1 nodes) vs visceral (visceral, regardless of other sites). Kaplan-Meier methods were used to analyze TTM. A stratified proportional hazards model with treatment group as a factor, stratified by PSADT, bone-sparing agent use, and loco-regional disease, was used to estimate HR and 95% CI. Results: Of those pts with metastases (APA vs PBO, respectively), 30% (52/175) and 40% (76/191) developed nodal metastases, while 57% (100/175) and 52% (100/191) developed bone metastases, and 13% (23/175) and 8% (15/191) developed visceral metastases. The HRs (APA vs PBO; 95% CI) for TTM for the intent-to-treat population were 0.19 (0.13-0.27) and 0.31 (0.23-0.41) for nodal and bone metastases, respectively (p < 0.0001). Conclusions: Treatment with APA markedly decreased the risk of metastases, regardless of the site of metastasis. The consistency of these results provides further evidence for the clinical benefit of APA in nmCRPC. Clinical trial information: NCT01946204.