ASCO 2018: A Randomized Study of Finite Abiraterone Acetate Plus Leuprolide Versus Leuprolide in Biochemically Recurrent Non-Metastatic Hormone Naïve Prostate Cancer

Chicago, IL ( Based on several phase III RCTs published in the last 12 months, we know that abiraterone acetate (AA) improves survival among men with metastatic hormone-naïve prostate cancer [1-2]. Prolonged androgen ablation with sustained ADT has detrimental effects on morbidity and may increase risk of mortality. Several years ago, level 1 evidence was published suggesting that intermittent androgen deprivation is an acceptable treatment option for patients with M0 hormone naïve prostate cancer [3], with no significant survival difference and improved quality of life versus continuous ADT. Taken together, the hypothesis for this phase II trial was that AA added to intermittent ADT will improve outcome without delaying testosterone recovery among patients with biochemical recurrence after definitive therapy for localized prostate cancer. At today’s ASCO 2018 annual meeting, Dr. Efstathiou presented the first results of this trial.

Patients with PSA recurrent, after definitive local treatment, M0 hormone naïve prostate cancer were randomized 1:1 to receive either 8 months of AA (1 g/per day) + prednisone (5 mg daily) + LHRHa vs LHRHa. Patient eligibility criteria included:
• PSA recurrent hormone naïve prostate cancer
• No evidence of disease by conventional imaging
• Prior definitive treatment of the primary tumor (radical prostatectomy or radiotherapy)
• Rising PSA of 0.2 confirmed by subsequent > 0.2 required after radical prostatectomy and nadir PSA +2 for prior radiotherapy
• Eugenic state (testosterone ≥150 ng/dL)

Patients were eligible to cross over upon progression (PSA relapse >1 ng/mL and/or metastatic local relapse). The primary endpoint was PSA free survival and the main secondary endpoints included time to testosterone recovery (≥150 ng/dL), PSA free survival difference following testosterone recovery, and safety. Sample size had 93% power to detect one year post treatment PSA free survival difference of 20 %. Stratification factors were radical prostatectomy vs radiation, PSA ≥ vs < 10, and time to recurrence ≥ vs < 3yrs. Patient enrollment was from February 2013 – July 2016, with a data analysis cutoff of January 2018.

There were 200 patients enrolled and 197 randomized: 99 patients treated with 8 months AA + LHRHa vs 98 patients in the LHRHa arm. The median age for the entire cohort was 65 (range 42- 85) years, median performance status 0, median PSA was 1 (0.3-33.3 ng/ml), and median testosterone was 346 (range 160-946 ng/dL). Nearly all patients (94%) underwent radical prostatectomy, with 65% of patients experiencing a PSA relapse by the time of analysis. The primary and secondary outcome results for this trial were as follows:
• Patients on 8 months of AA + LHRHa had median PSA free survival 28.3 months (range 24.2—35.4) vs 21.1 (19.1-27.2) for LHRHa patients (HR 0.62, 95%CI 0.44-0.88).
• Median time to testosterone recovery for AA + LHRHa was 13.1 months (95%CI 13.0-13.3) vs 12.9 (95%CI 11.0-13.1) for LHRHa
• Median time to PSA relapse following testosterone recover for AA + LHRHa was 13.8 months vs 9 months for LHRHa (HR 0.70, 95%CI 0.49-1.00)

AA + LHRHa treatment outcome was favorable regardless of pretreatment PSA, Gleason Score, pathology, time to relapse from treatment, definitive treatment type, including if patients underwent radical prostatectomy + radiotherapy. No Grade 4 adverse events (AE) or new safety concerns reported. Grade 3 AEs included six patients with arterial hypertension (n=5 AA + LHRHa arm), and four patients with liver function test elevation (all AA + LHRHa arm).

Dr. Efstathiou concluded this presentation with several take home messages for this trial:
• These findings support the 8-month treatment with Abiraterone Acetate plus LHRHa in M0 hormone naïve prostate cancer
• There was a significant improvement in PSA free survival compared to LHRHa
• There was no significant delay in testosterone recovery, with a significantly delayed time to PSA relapse following testosterone recovery.

Clinical trial information: NCT01786265

Presented by: Eleni Efstathiou, The University of Texas MD Anderson Cancer Center, Houston, TX

Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md, at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA

1. Fizazi K, Tran N, Fein L, et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2017;377(4):352-360.
2. James ND, de Bono JS, Spears MR, et al. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N Engl J Med. 2017;377(4):338-351
3. Crook JM, O’Callaghan CJ, Duncan G, et al. Intermittent androgen suppression for rising PSA level after radiotherapy. N Engl J Med 2012;367(10):895-903.

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