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
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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.