ASCO 2017: Neoadjuvant randomized trial of degarelix (Deg) ± cyclophosphamide/GVAX (Cy/GVAX) in men with high-risk prostate cancer (PCa) undergoing radical prostatectomy (RP)

Chicago, IL (UroToday.com) There has been a paradigm shift over the last several years regarding treating high risk patients up front with multimodal therapy with the hope of long-term survival durability. Along this line of thinking, Dr. Emmanuel Antonarakis and colleagues presented results of their neoadjuvant randomized trial of degarelix with or without cyclophosphamide/GVAX (Cy/GVAX) in men with high-risk prostate cancer undergoing radical prostatectomy at the prostate cancer poster session at the 2017 ASCO annual meeting. GVAX-Prostate is a GM-CSF–secreting allogeneic cellular vaccine, whose immunogenicity may be enhanced by androgen ablation as well as low-dose cyclophosphamide.

For this trial, men with high-risk prostate cancer (T1c–3bN0M0, Gleason 7–10) were randomized 1:1 to degarelix (240 mg SQ) vs. cyclophosphamide (200 mg/m2IV)/GVAX (2.5×108 PC3 cells, 1.6×108 LNCaP cells) given 2 weeks before degarelix. All patients then had a radical prostatectomy 2 weeks after degarelix. CD8+ T cell and Treg densities in the primary tumor were quantified by immunohistochemistry. Clinical endpoints were time-to-PSA-relapse, time-to-next-therapy, and time-to-metastasis. The study was powered (α = 0.05, β = 0.18) to show a two-fold increase in mean CD8+ density with Cy/GVAX→degarelix (Arm B) vs. degarelix (Arm A). There were 28 men enrolled in this trial (Arm A, n=15; Arm B, n=13), along with 20 patients not receiving neoadjuvant therapy who underwent radical prostatectomy in order to provide untreated radical prostatectomy specimens. Baseline variables were balanced across study arms, including 64% with Gleason ≥8 disease, 56% with pT3b tumors, and 18% were pN1. There were nonsignificant increases in CD8+ and Treg in Arm B vs. Arm A, and statistically significant increases in CD8+ and Treg densities in both arms A and B compared to the control group. Outcomes were better in Arm B vs Arm A with respect to time-to-PSA-relapse (HR 0.42, 95%CI 0.13–1.38) and time-to-next-therapy (HR 0.43, 95%CI 0.13–1.39), although these results were not statistically significant.

In conclusion, the investigators noted that intratumoral immune infiltrates were marginally augmented by Cy/GVAX→degarelix vs. degarelix alone, while CD8+ and Treg densities were significantly greater in both study arms vs. the control group. These results support the immunogenic effects of androgen ablation, and the authors note that semi quantitative PD-L1 analysis and exploration of serum anti-prostate antibodies and tissue immunological profiles are currently ongoing.
Clinical trial: NCT01696877

Presented By: Emmanuel S. Antonarakis, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD, USA

Co-Authors: Marianna Zahurak, Edward M. Schaeffer, Alan W. Partin, Ashley Ross, Mohamad Allaf, Jeffrey Tosoian, Thomas Nirschl, Carolyn Chapman, Tanya Skelton O'Neal, Haiyi Cao, Jennifer N. Durham, Gunes Guner, Javier Baena Del Valle, Onur Ertunc, Angelo Demarzo, Charles G. Drake

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
Twitter: @zklaassen_md

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA
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