ASCO GU 2018: Abiraterone acetate plus prednisone 5 mg daily in metastatic castration-naïve prostate cancer (mCNPC): Detailed safety analyses from the LATITUDE phase III trial

San Francisco, CA ( Dr. Fizazi and colleagues presented a detailed safety analysis of abiraterone acetate + prednisone among patients with mCNPC at the prostate cancer poster session at GU ASCO 2018. Based on results of the LATITUDE phase III RCT published last year [1], abiraterone acetate + prednisone added to androgen deprivation therapy (ADT) improves overall survival (OS) in newly diagnosed mCNPC patients. However, abiraterone acetate has been previously coadministered with prednisone at a dose of 10 mg daily. As a lower dose of prednisone (5 mg daily) was used in LATITUDE, the objective of this study was to conduct additional safety analyses.

LATITUDE comprised 1199 patients with newly diagnosed, high-risk mCNPC (≥ 2 of 3 risk factors: Gleason ≥ 8, ≥ 3 bone lesions, visceral metastases) who were randomized 1:1 to abiraterone acetate (1 gm daily) + prednisone (5 mg daily) + ADT or placebos of abiraterone acetate + prednisone + ADT: median treatment duration was 24 and 14 months, respectively. Safety analyses focused on key mineralocorticoid excess-related adverse events (AEs), namely hypertension and hypokalemia.

The authors found that increased hypertension with 5 mg/d prednisone with abiraterone acetate + ADT (relative risk, 1.6 [95%CI, 1.4-1.9]) was similar to prior studies using 10 mg/d of prednisone (COU-AA-301 [2]: relative risk 1.4 [95%CI 0.9-2.0]; COU-AA-302 [3]: relative risk 1.6 [95%CI 1.2-2.1]). Among the grade 3/4 hypertension events, 87% (109/126 [abiraterone acetate + prednisone + ADT]) and 83% (52/63 (placebos + ADT) resolved to grade ≤ 2. There were few cerebrovascular events: abiraterone acetate + prednisone + ADT, n=5; placebos + ADT, n=9. The protocol allowed increasing dose of prednisone to 10 mg daily for mineralcorticoid-related AEs, but most grade 3/4 hypertension events were managed only by supplemental antihypertensives. Prior use of antihypertensives at study entry was predictive of grade 3/4 hypertension in both treatment arms (relative risk: 1.85; 95% CI, 1.14-3.01). Grade 3/4 hypokalemia increased with abiraterone acetate + prednisone + ADT (10.4% [62/597]) vs placebos + ADT (1.3% [8/602]). Furthermore, 89% (55/62) and 100% (8/8) of these events improved to grade ≤ 2. Less than 1% of patients in either arm discontinued therapy for mineralcorticoid-related AEs.

Dr. Fizazi concluded that based on an in-depth analysis of LATITUDE data, there is confirmation regarding the safety of 5 mg/d prednisone with abiraterone acetate + ADT and helps provide practical treatment guidance for managing mCNPC.

Speaker: Karim Fizazi, Gustave Roussy Institute of Oncology, University of Paris-Sud, Villejuif, France

Co-Authors: Namphuong Tran, Luis Enrique Fein, Nobuaki Matsubara, Anders Bjartell, Luca Galli, Jae-Lyun Lee, Danish Mazhar, Scott A. North, David Olmos, Henrik Suttmann, Qing Zou, Susan Li, Jason L. Martin, Youn C. Park, Giri Sulur, Kris Deprince, Peter De Porre, Kim N. Chi

Written by: Zachary Klaassen, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter:@zklaassen_md at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA

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. de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011;364(21):1995-2005.
3. Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368(2):138-148.