Third analysis of a randomized trial of finite abiraterone acetate (AA) plus LHRH agonist (LHRHa) versus LHRHa in biochemically recurrent, non-metastatic hormone-naïve prostate cancer (M0HNPC).

Abstract

135 Background: In pre-operative studies, a short duration of AA + LHRHa produced marked cytoreduction in a subset of men with high-risk prostate cancer (PCa). However, in M0HNPC, androgen signaling inhibition (ASI) is reserved for men with short PSA doubling time. We reasoned that the subset of men who experience cytoreduction with pre-operative AA + LHRHa would also benefit from a short duration of AA + LHRHa at PSA recurrence. This report is a one-year follow-up of our second analysis (ASCO Annual Meeting 2018; PMID 34536949). Methods: FINITE is a phase II trial that randomized (1:1) to two treatment groups, 8 months of LHRHa alone or LHRHa plus AA 1000 mg and prednisone 5 mg daily (NCT01786265). Eligible patients had a rising PSA after definitive therapy and no prior systemic therapy. At disease progression, men were eligible for crossover to 8 months of the alternative therapy. The primary endpoint was PSA-free survival at 12 months (≤ 0.1 ng/dL). Time to PSA progression was calculated from date of initial treatment to date of PSA progression, defined as first occurrence of a rising PSA, if PSA remained detectable after treatment, or when the PSA ≥ 1 ng/dL, if it was undetectable after treatment and confirmed 4 weeks thereafter. The probabilities of PSA progression were defined using the Kaplan-Meier method. Results: 199 men were randomized, and 197 received initial treatment (LHRHa = 99, LHRHa + AA = 98). Median age at enrollment was 65 years, median PSA was 0.95 ng/dL (range 0.1 – 33.3), and median testosterone was 342.5 ng/dL (10-986). At data cut-off (October 1, 2021), men who received LHRHa + AA were more likely to be PSA-free 12 months after completing treatment (34% vs. 19%, p = 0.02). 168 men (85%) had experienced PSA progression, and median time to PSA progression was 24.3 months for entire cohort. Receipt of LHRHa + AA was associated with longer time to PSA progression than LHRHa alone (27.2 vs. 19.9 months, p = 0.003). Conclusions: Our findings support that finite treatment with AA + LHRHa produces more durable disease-free survival than LHRHa. The finite duration of AA + LHRHa is a toxicity-sparing approach that may allow for a transition from a treatment to curative paradigm for a subset of men with M0HNPC. Further analyses will aim to link the subset of men who benefit from finite AA + LHRHa between localized high-risk PCa and M0HNPC. Clinical trial information: NCT01786265.