A phase II trial of enzalutamide (Enz) with 5-alpha reductase inhibitors (5-ARI) as an androgen deprivation therapy (ADT)–sparing approach for older men with castration-sensitive prostate cancer (CSPC).

5089 Background: Older men with prostate cancer who have aging-related conditions are at high risk for adverse events (AEs) from ADT. 5-ARI inhibit the conversion of testosterone to dihydrotesterone and could be synergistic with Enz. In this phase II study, we evaluated Enz and Dutasteride (Dut) or Finasteride (Fin) in lieu of ADT for older men with CSPC who are at risk of AEs from ADT. Methods: Eligible patients were ≥65 years (y); deemed “not fit” by geriatric assessment (GA) or at high risk for side effects from ADT as determined by the treating physician; had metastatic (M1) or non-metastatic (M0) CSPC with a PSA doubling time ≤9 months and testosterone >50ng/dl. Enz 160 mg daily and Dut 0.5mg daily or Fin 5mg daily were administered until disease progression per Prostate Cancer Clinical Trials Working Group 2 guidelines. The primary study endpoint is PSA progression free survival (PFS). Key secondary endpoints include time to PSA nadir, absolute PSA nadir and evaluation of safety and toxicity of study treatments per CTCAE V4.0. Results: 43 men enrolled in the study. At study entry, subjects had the following baseline characteristics: median age was 78 y (range 66-94); 93% had ECOG 0-1; 63% had M1 CSPC with 30% of them having high volume disease per CHAARTED criteria; 23% had Gleason ≥ 8 CSPC; median PSA was 11.4 ng/ml (2-145), and median testosterone level was 342 ng/dl (56-639). Baseline GA at study entry showed that 18.6% had Instrumental Activity of Daily Living impairment; 9.8% had recent falls; 52.4% had Short Physical Performance Battery impairment; 40.5% had Older American Resources and Services (OARS) physical health and 31% had OARS medical social support impairments; 11.6% had Geriatric Depression Scale impairments; 65.9% had either Blessed Orientation-Memory-Concentration or Montreal Cognitive Assessment impairments; and 34.9% had Vulnerable Elders Survey-13 impairments. At a median follow-up of 5.9 y, 23 pts (53%) remained on study treatment and the median PSA PFS has not been reached for the entire group. The median time to PSA nadir was 8.1 months, with median PSA nadir at 0.02 ng/ml (range 0-2.75) and 98% having ≥90% PSA decline. The five most common any grade AE was fatigue (88%), gynecomastia (72%), hot flashes (42%), hypertension (40%), and falls (37%). No subject had treatment-related Grade 4 or 5 AEs. Four (9.3%) subjects withdrew treatment, 21% held treatments and 30.2% reduced dose of treatment due to AEs. Conclusions: The combination treatment with Enz and Dut/Fin appears to have clinical efficacy for older patients with CSPC who are at high risk for AEs from ADT. Clinical trial information: NCT02213107 .