As reported in The Lancet Oncology by Karim Fizazi, MD, PhD, and colleagues, the final overall survival analysis in the phase III LATITUDE trial has shown a significant benefit with the addition of abiraterone acetate plus prednisone to androgen deprivation therapy (ADT) in newly diagnosed, high-risk, metastatic, castration-sensitive prostate cancer.¹ The trial supported the 2018 approval of abiraterone acetate plus prednisone in this setting, with interim analysis showing progression-free and overall survival benefits.

Karim Fizazi, MD, PhD

Phase III LATITUDE Trial

In the double-blind trial, 1,199 patients from 235 sites in 34 countries were randomly assigned between February 2013 and December 2014 to receive abiraterone acetate (1,000 mg once daily) plus prednisone (5 mg once daily) and ADT (n = 597) or placebo plus ADT (n = 602). After the results of the first interim analysis, the study was unblinded and patients in the placebo group were allowed to cross over to receive abiraterone acetate and prednisone plus ADT treatment in accordance with a protocol amendment (February 2017) in an open-label extension of the study. 

Overall Survival

The final analysis had a data cutoff in August 2018. Median follow-up was 51.8 months. At the time of final analysis, 72 patients had crossed over to abiraterone acetate plus prednisone from the placebo group. Death occurred in 46% of the abiraterone acetate group vs 57% of the placebo group. Median overall survival was 53.3 months (95% confidence interval [CI] = 48.2 months—not reached) vs 36.5 months (95% CI = 33.5–40.0 months), with a hazard ratio of 0.66 (P < .0001). Improvement in overall survival with abiraterone acetate plus prednisone was observed in most patient subgroups, except for patients with Eastern Cooperative Oncology Group performance status of 2 and those with Gleason scores < 8. Consistent with findings in the interim analysis, the abiraterone acetate group had significant improvements in time to pain progression, symptomatic skeletal-related events, chemotherapy initiation, subsequent therapy for prostate cancer, and prostate-specific antigen progression.

Adverse Events

The most common grade 3 or 4 adverse events were hypertension (21% in the abiraterone acetate group, 10% in the placebo group, and 4% among the 72 patients crossing over from placebo to abiraterone acetate plus prednisone) and hypokalemia (12%, 2%, and 3%, respectively). Serious adverse events occurred in 32%, 25%, and 6% of patients, respectively. Treatment-related deaths occurred in 3 patients (< 1%) each in the abiraterone acetate group (due to gastric ulcer perforation, sudden death, and cerebrovascular accident) and the placebo group (due to sudden death, cerebrovascular accident, and pneumonia), with none occurring in the crossover group.

The investigators concluded, “The combination of abiraterone acetate plus prednisone with ADT was associated with significantly longer overall survival than placebos plus ADT in men with newly diagnosed high-risk [metastatic, castration-sensitive prostate cancer] and had a manageable safety profile. These findings support the use of abiraterone acetate plus prednisone as a standard of care in patients with high-risk metastatic castration-sensitive prostate cancer.” ■

DISCLOSURE: The study was funded by Janssen Research & Development. Dr. Fizazi has received personal fees from Amgen, Astellas, AstraZeneca, Bayer, Clovis, Curevac, Essa, Genentech, Janssen, Merck Sharp and Dohme (MSD), Orion, and Sanofi. For full disclosures of all study authors, visit 
thelancet.com.

REFERENCE

1. Fizazi K, Tran NP, Fien L, et al: Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE). Lancet Oncol 20(5): 686-700, 2019.