While enzalutamide has demonstrated significant survival benefits in the setting of metastatic castration-resistant prostate cancer (CRPC), and abiraterone was recently demonstrated to benefit patients with metastatic hormone-sensitive prostate cancer (hsPCa), there is no evidence suggesting the use of these agents in the adjuvant setting in the absence of metastatic disease. Prior studies assessing ADT in this setting did not demonstrate survival benefit.
This was a phase II study primarily assessing safety, with plans for a phase III study. High-risk PCa (HRPCa) was defined as: ≥pT3a, GS≥8, initial PSA ≥20 ng/mL, positive lymph nodes (LN) pN+, or ≥35% chance of biochemical recurrence (BCR) at 5-yrs based on MSKCC’s nomogram. Men with HRPCa who had an undetectable PSA within 3 months from RP were eligible for inclusion; KPS >= 70 and adequate organ function was also required. Prior use of ADT, AR directed therapy or RT was not allowed. This was not a randomized trial, so all men received Enzalutamide 160mg PO daily in 28-day cycles until disease progression (BCR defined as PSA ≥0.2ng/mL on 2 consecutive lab results or any PSA rise that resulted in subsequent therapy), intolerability, consent withdrawal, or study completion at 24 months. With an accrual goal of 40 men, they recruited 42 men for the study.
Of the 42 men that enrolled, the median age was 59 (range 43-70). Median initial PSA was 8.2 ng/dL (range 2-77). On final prostatectomy pathology: 50% had pT3b; 52% positive margins; 24% had pN+ disease. Many of these men would have been considered for adjuvant XRT or even ADT for node-positive disease.
Only 37 (88%) men completed 24 planned cycles - of the 5 pts who did not complete all cycles, 3 withdrew consent for toxicity (2 had G3 fatigue, 1 had G3 fatigue and arthralgias/myalgias), 1 had rising PSA requiring subsequent therapy, and 1 had financial concerns.
As the study’s primary goal was to assess safety: most common adverse events (AE) were Gynecomastia or breast/nipple soreness/pain, Fatigue, Neurologic, Weight gain, Arthralgia/myalgia, Hyperglycemia, Alopecia, Hot flashes/flushing. While side effect were common, only 4 patients had Grade 3 AE- 3 fatigue, 1 arthralgia. Overall adverse events were similar to the medication use in other disease states.
Median follow-up was 31 months (range 2.5-44.5). During that time, 37 (88%) men remained free of BCR. Of the 5 pts who developed BCR, 4 completed all 24 months on therapy. Median time to BCR in these 5 patients was 31 months (range 13-40).
Unfortunately, due to the limited follow-up of 2.5 years and the non-randomized nature of the phase II trial, oncologic efficacy is uncertain. Many of these patients may never have progressed and were treated unnecessarily. However, without doubt, especially some of the men with node-positive disease, likely benefited from Enza in an adjuvant setting.
Ongoing studies, and hopefully prospective Phase III studies, wil be better able to answer these important questions prior to uptake in regular clinical practice.
Speaker: Moshe Ornstein, MD, MA
Co-Authors: Andrew J. Stephenson, Paul Elson, Allison Janine Tyler, Pam Profusek, Kimberly D Allman, Pedro C. Barata, Cristina Magi-Galluzzi, Amr Farouk Fergany, Robert Stein, Khaled Fareed, Georges-Pascal Haber, Steven C. Campbell, Jihad Kaouk, Petros Grivas, Brian I. Rini, Eric A. Klein, Jorge A. Garcia
Institution(s): Cleveland Clinic, Cleveland, OH
Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA