ASTRO 2022: Abiraterone, ADT, and Radiotherapy for Localized Intermediate/High Risk Prostate Cancer: Long-Term Follow-Up of the RAD1 Phase 2 Trial

(UroToday.com) The 2022 ASTRO annual meeting featured a prostate cancer session, including a presentation by Dr. Macklin Nguyen discussing long-term follow-up of the RAD1 phase 2 trial, specifically abiraterone, androgen deprivation therapy (ADT), and radiotherapy for localized intermediate/high risk prostate cancer. Radiotherapy combined with ADT is an established standard of care for high risk non-metastatic prostate cancer. Ongoing studies are evaluating whether treatment intensification of systemic therapy can improve outcomes. Recent data from a STAMPEDE meta-analysis showed improvement in metastasis-free survival with addition of abiraterone.1 In 2015, Dr. Nguyen and colleagues reported the first study combining neoadjuvant and concurrent abiraterone with LHRH agonist in patients undergoing primary radiotherapy for localized prostate cancer [2]. At the 2022 ASTRO annual meeting, they presented long-term follow up of this small phase II trial.

 Patients with intermediate (Gleason 7 or PSA 10-20 ng/mL), high risk (cT3/T4, Gleason 8-10 or PSA >20 ng/mL) or node positive prostate cancer were enrolled on a single-arm phase 2 trial. Study therapy consisted of 24 weeks of LHRH agonist (without anti-androgen) combined with abiraterone (1000 mg daily), and prednisone. After 12 weeks of neoadjuvant therapy, patients underwent conventional dose-escalated intensity modulated radiotherapy (IMRT). Duration of adjuvant ADT was per treating physician discretion, generally 6 months for intermediate and 24 months for high risk disease. The primary endpoint was to determine the safety of concurrent abiraterone with radiotherapy (previously reported). Event outcomes (secondary endpoints) were calculated from start of study therapy to biochemical recurrence (Phoenix definition), distant metastasis, death from any cause, and death from prostate cancer.

 From 2011-2013, 22 patients with high risk (n=19) or intermediate risk (n=3) prostate cancer were enrolled, negative for distant metastatic disease by bone scan and CT. Patient details included age (median 62, range 43-81), T classification (T1c/T2, n=15; T3, n=7), Gleason sum (7, n=10; 8-10, n=12), and PSA (median 20 ng/mL, range 4.8-155). Three were node positive, and 8 had high risk criteria meeting eligibility for the recent STAMPEDE trials (node positive or at least two criteria: T3/T4, Gleason 8–10, and PSA ≥ 40 ng/mL). There were 2 patients that withdrew before completing study therapy and were excluded from analyses. The median radiotherapy dose was 81 Gy and all but one patient received pelvic nodal radiotherapy (median dose 50.4 Gy). The median PSA nadir was 0 (range <0.03-0.2) ng/mL, and at a median follow up of 109 months (IQR 96-115), three patients have died (one of prostate cancer, two other causes), three had biochemical recurrence, and three had distant metastases. Kaplan-Meier 8-year biochemical recurrence-free survival was 81%, distant metastasis-free survival 78%, overall survival 84%, prostate cancer-specific survival 94%:

 

ASTRO 2022 Nguyen_0 

 

Dr. Nguyen concluded this presentation discussing long-term follow-up of the RAD1 phase 2 trial with the following take-home messages:

  • In this small cohort of patients with intermediate/high risk prostate cancer with a median follow-up of more than 9 years, combination therapy with abiraterone, ADT and radiotherapy was well-tolerated and associated with excellent long-term disease control outcomes
  • These findings are in line with recent STAMPEDE analyses in this patient population supporting intensification of therapy with abiraterone
  • Further larger studies are warranted to refine patient selection for this approach

 

Presented by: Macklin H. Nguyen, MD, University of Washington, Department of Radiation Oncology, Seattle, WA

Co-Authors: J. J. Liao1, E. Mostaghel2, K. J. Russell3, B. Dalkin3, W. Ellis3, D. Lin3, J. Wright3, G. Schade3, Y. A. Nyame3, E. Y. Yu3, P. Nelson3, P. Grivas3, M. Schweizer3, H. H. Cheng3, T. Yezefski3, J. E. Hawley3, J. Chen1, E. S. Weg3, and B. Montgomery41University of Washington, Department of Radiation Oncology, Seattle, WA, 2Seattle Cancer Care Alliance, Seattle, WA, 3University of Washington, Seattle, WA, 4University of Washington, Seattle, WA, United States

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 Radiation Oncology (ASTRO) Annual Hybrid Meeting, San Antonio, TX, Sat, Oct 22 – Wed, Oct 26, 2022.

References:

  1. Attard G, Murphy L, Clarke NW, et al. Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: A meta-analysis of primary results from two randomized controlled phase 3 trials of the STAMPEDE platform protocol. Lancet. 2022;399:447-460.
  2. Cho E, Mostaghel E, Russell KJ, et al. External beam radiation therapy and abiraterone in men with localized prostate cancer: safety and effect on tissue androgens. Int J Radiat Oncol Biol Phys. 2015;92(2):236-243.