Molecular determinants of prostate specific antigen (PSA) kinetics and clinical response to apalutamide (APA) in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) in SPARTAN.

Abstract

5521 Background: In SPARTAN, APA + androgen deprivation therapy (ADT) prolonged metastasis-free survival (MFS) and improved PSA kinetics over placebo (PBO) + ADT in high-risk nmCRPC. All molecular subtypes derived benefit in MFS from APA (Feng FY, et al. ASCO GU 2019; abstract 42). We evaluated the association of PSA decline and efficacy outcomes in SPARTAN pts with different molecular subtypes. Methods: Gene expression from archival primary tumors (biomarker population) was assessed with the DECIPHER platform (Decipher Biosciences, Inc.) and stratified into genomic classifier (GC) high- and low-to-average risk using GC score > 0.6 and ≤ 0.6, respectively, and ADT-resistant or -sensitive basal or luminal A/B (PAM50 classifier) subtypes. PSA nadir and confirmed PSA decline (Table) were assessed in APA pts overall and at 3, 6, and 12 mo. Associations between molecular subtypes and outcomes were assessed. Results: Of 233 available samples, 154 were from APA pts; 49% of APA pts had high GC score and 66% had basal subtype. PSA levels at baseline were similar across all subtypes. Regardless of GC score or basal/luminal subtype, > 50% of patients achieved ≥ 90% reduction in PSA with APA. PSA declined faster and PSA reduction was deeper at 6 mo (Table) in GC low to average vs GC high risk and luminal vs basal subtypes. Overall, only luminal vs basal subtypes had a significantly higher % of pts with ≥ 90% PSA decline (Chi square p = 0.037). In luminal pts, deeper PSA decline with APA was consistent with improved MFS vs basal pts. In GC high pts, MFS benefit with APA was similar to that in GC low to average pts despite lower PSA decline. Although GC low to average and luminal pts had more rapid and deeper PSA responses than GC high or basal pts, respectively, all pts derived MFS benefit. Association of long-term outcomes with PSA decline in these molecular subtypes will be presented. Conclusions: In SPARTAN, all molecular subtypes of pts with nmCRPC treated with APA + ADT had MFS benefit and rapid and sustained PSA decline. PSA responses were deepest and most rapid in GC low to average and luminal subtypes. Clinical trial information: NCT01946204 . [Table: see text]