(UroToday.com) The 2022 GU ASCO Annual meeting included a prostate cancer trials in progress session featuring Dr. Adam Kibel presenting PROTEUS, a randomized, double-blind, placebo-controlled, phase 3 trial of apalutamide plus ADT versus placebo plus ADT prior to radical prostatectomy in patients with localized or locally advanced high-risk prostate cancer. In patients with localized high-risk prostate cancer, disease recurrence rate following RP is ~50%.1 Treatment with androgen blockade before RP can reduce tumor burden post RP.2-4 This study examines if 12 months of perioperative apalutamide + ADT treatment before and after RP with pelvic lymph node dissection in localized/locally advanced high-risk prostate cancer improves pathologic complete response (pCR) rate and metastasis-free survival (MFS) vs placebo + ADT.
PROTEUS, an international multicenter study, is enrolling ~2000 patients with localized/locally advanced high-risk/very high-risk prostate cancer who are candidates for RP with pelvic lymph node dissection over 3 years at > 203 sites in 18 countries. Stratification variables include: Gleason score (7 vs ≥ 8), pelvic node status (N0 vs N1), international region. Randomization will be 1:1 to apalutamide (240 mg/d) + ADT or placebo + ADT. Patients receive 6-month neoadjuvant treatment followed by RP and then 6 months’ adjuvant treatment.
The PROTEUS study design is as follows:
The primary endpoints are pCR rate and MFS; in addition to MFS based on conventional imaging, MFS based on PSMA PET or conventional imaging will be assessed as a separate endpoint. Both pCR and MFS are assessed by blinded independent central review. Conventional imaging by CT or MRI and bone scan are done at screening, within 4 weeks after RP, at biochemical failure, and then every 6 months after biochemical failure until distant metastasis or death. During the direct perioperative period, apalutamide/placebo is stopped 2 weeks prior to planned RP and then resumed 4 weeks after RP if post-RP imaging has been conducted to assess for lymphocele and disease progression and resolution to grade ≤ 1 of any clinically significant adverse events considered related to RP. To reflect evolving standard of care, the following protocol amendments were added:
- PSMA-PET imaging at 3 months post adjuvant treatment, at biochemical failure, and every 6 months until distant metastasis or death
- Cardiovascular and thrombotic risk assessment at screening, prior to, and after RP
- Guidance for standard thrombotic prophylaxis in the perioperative setting
An independent data monitoring committee will review trial data. The study start date was June 11, 2019, with a total time of 7.5 years (3 years of accrual + 4.5 years of follow-up).
Presented by: Adam S. Kibel, MD, Brigham & Women's Hospital, Boston, MA
Co-Authors: Martin Gleave, Sabine D. Brookman-May, Won Kim, Christopher P. Evans, Eleni Efstathiou, Philip W. Kantoff, Ashley Ross, Neal D. Shore, Alberto Briganti, Boris A. Hadaschik, Axel Heidenreich, Oliver Brendan Rooney, Shaozhou Ken Tian, Lisa Wetherhold, Weichun Xu, J. Kellogg Parsons, Kesav Yeruva, Mary-Ellen Taplin
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, Thursday Feb 17 – Saturday Feb 19, 2022
References:
- Kane CJ, Presti Jr JC, Amling CL, et al. Changing nature of high risk patients undergoing radical prostatectomy. J Urol. 2007 Jan;177(1):113-117.
- Taplin ME, Montgomery B, Logothetis CJ, et al. Intense androgen-deprivation therapy with abiraterone acetate plus leuprolide acetate in patients with localized high-risk prostate cancer: results of a randomized phase II neoadjuvant study. J Clin Oncol. 2014;32(33):3705-3715.
- McKay RR, Montgomery B, Xie W, et al. Post prostatectomy outcomes of patients with high-risk prostate cancer treated with neoadjuvant androgen blockade. Prostate Cancer Prostatic Dis. 2018 Sep;21(3):364-372.
- Efstathiou E, Davis JW, Pisters L, et al. Clinical and biological characterization of localized high-risk prostate cancer: Results of a randomized preoperative study of a luteinizing hormone-releasing hormone agonist with or without abiraterone acetate plus prednisone. Eur Urol. 2019;76(4):418-424.