Patients in LATITUDE had to be newly diagnosed with prostate cancer and be high-risk, defined as meeting at least two of three criteria: (i) Gleason score ≥8, (ii) presence of ≥3 lesions on bone scan, (iii) presence of measurable visceral lesions. Patients were stratified by the presence of visceral disease (yes/no) and ECOG performance status (0, 1 vs 2) and then randomized 1:1 to either ADT + AA (1000 mg daily) + prednisone (5 mg) (n=597) or ADT + placebo (n=602). For this second preplanned analysis, median time to subsequent prostate cancer therapy and chemotherapy, as well as a post hoc exploratory endpoint, time to life-prolonging therapy, were analyzed by stratified proportional hazards model.
At a median follow-up of 41.4 months, the median treatment exposure was 25.8 months for patients receiving ADT + AA + prednisone vs 14.4 months for those receiving ADT + placebo; treatment was ongoing for 34% of patients on ADT + AA + prednisone and 12% for those on ADT + placebo. Among ADT + placebo patients, 60 crossed over to receive ADT + AA + prednisone, with a median ADT + AA + prednisone exposure of 2 months (n=57, 95% still on ADT + AA + prednisone). The most common reason for discontinuation of treatment was progressive disease: 40% for ADT + AA + prednisone patients and 64% for ADT + placebo patients. For patients on ADT + AA + prednisone, 37% received subsequent therapy and 26% life-prolonging therapy. For patients on ADT + placebo, 58% received subsequent therapy and 45% life-prolonging therapy. The life-prolonging therapies received were as follows:
The median duration of first life-prolonging therapy was 3.7 months for those on ADT + AA + prednisone (n = 155) and 5.7 months for those on ADT + placebo (n = 268). Compared with patients receiving ADT + placebo, those receiving ADT + AA + prednisone had a delayed time to:
- Life-extending prostate cancer therapy: HR 0.398, 95%CI 0.326-0.486
- Chemotherapy: HR 0.471, 95%CI 0.378-0.586
- Subsequent prostate cancer therapy: HR 0.428, 95%CI 0.361-0.507
In addition to the durable oncologic/survival outcomes associated with patients receiving ADT + AA + prednisone for newly diagnosed high-risk metastatic castration-naïve prostate cancer, the results of this study suggest that these patients also benefit from delaying the time to subsequent therapy, life-prolonging therapy, and chemotherapy. These results are reported even in the setting of most patients initially receiving ADT + placebo crossing over to ADT + AA + prednisone or other life-prolonging subsequent therapy.
Clinical trial information: NCT01715285
1. Fizazi K, Tran N, Fein L, et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2017;377(4):352-360.
2. James ND, de Bono JS, Spears MR, et al. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N Engl J Med. 2017;377(4):338-351.
Presented by: Kim N. Chi, MD, BC Cancer Agency - Vancouver Centre, Vancouver, BC, Canada
Co-Authors: Namphuong Tran, Susan Feyerabend, Nobuaki Matsubara, Mustafa Ozguroglu, Luis Enrique Fein, Alfredo Rodríguez Antolín, Boris Yakovlevich Alekseev, Giri Sulur, Andrew Protheroe, Peter De Porre, Susan Li, Youn C. Park, Suneel Mundle, Karim Fizazi; Janssen Research & Development, Los Angeles, CA; Studienpraxis Urologie, Nürtingen, Germany; National Cancer Center Hospital East, Chiba, Japan; Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey; Instituto de Oncología de Rosário, Rosário, Argentina; Hospital Universitario 12 de Octubre, Madrid, Spain; P.A. Hertsen Moscow Cancer Research Institute, Moscow, Russian Federation; Oxford University Hospitals Foundation NHS Trust, Oxford, United Kingdom; Janssen Research & Development, Beerse, Belgium; Janssen Research & Development, Spring House, PA; Janssen Research & Development, Raritan, NJ; Gustave Roussy, University of Paris Sud, Villejuif, France
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