LATITUDE Trial: Adding Abiraterone and Prednisone to Androgen-Deprivation Therapy in Metastatic Castration-Sensitive Prostate Cancer
As reported in the Plenary Session at the 2017 ASCO Annual Meeting and in The New England Journal of Medicine by Fizazi et al, the phase III LATITUDE trial has shown that the addition of abiraterone acetate (Zytiga) and prednisone to androgen-deprivation therapy resulted in marked improvements in overall and progression-free survival in patients with newly diagnosed castration-sensitive metastatic prostate cancer.
Study Details
In the double-blind trial, 1,199 patients from 235 sites in 34 countries in Europe, the Asia-Pacific region, Latin America, and Canada were randomized between February 2013 and December 2014 to receive androgen-deprivation therapy plus either abiraterone acetate at 1,000 mg daily and prednisone at 5 mg daily (n = 597) or dual matching placebos (n = 602). The two primary endpoints were overall survival and radiographic progression-free survival.
Improved Overall and Progression-Free Survival
At the first planned interim survival analysis (when 48% of deaths for final survival analysis had occurred), the median follow-up was 30.4 months. On the basis of the findings in the interim analysis, the independent data and safety monitoring committee recommended the trial be unblinded to allow crossover from the placebo group to abiraterone treatment. Median overall survival was not reached in the abiraterone group vs 34.7 months in the placebo group (hazard ratio [HR] = 0.62, P < .001). Overall survival at 3 years was 66% vs 49%.
Median radiographic progression-free survival was 33.0 months vs 14.8 months (HR = 0.47, P < .001). Overall and progression-free survival benefits in the abiraterone group were consistent across nearly all prespecified subgroups. In total, 21% of the abiraterone group and 41% of the placebo group received subsequent life-prolonging therapies after disease progression, with docetaxel being the most common treatment in both groups.
Secondary Endpoints
The abiraterone group had significantly better outcomes on all secondary efficacy endpoints, including median times to pain progression (not reached vs 16.6 months, HR = 0.70, P < .001), prostate-specific antigen (PSA) progression (33.2 vs 7.4 months, HR = 0.30, P < .001), next symptomatic skeletal event (not reached vs not reached, HR = 0.70, P = .009), initiation of chemotherapy (not reached vs 38.9 months, HR = 0.44, P < .001), and subsequent prostate cancer therapy (not reached vs 21.6 months, HR = 0.42, P < .001). An exploratory analysis showed PSA response (reduction ≥ 50% from baseline) in 91% vs 67% of patients (odds ratio = 1.36, P < .001).
Adverse Events
The most common adverse events of any grade in the abiraterone group were hypertension (32% vs 22%), hypokalemia (20% vs 4%), back pain (18% vs 20%), and increased alanine transaminase (16% vs 13%). Grade 3 or 4 adverse events occurred in 63% of the abiraterone group vs 48% of the placebo group, with mineralocorticoid-related toxicities being the most common and occurring more frequently in the abiraterone group; grade 3 and 4 hypertension occurred in 20% vs 0% and 10% vs 0.2% and grade 3 and 4 hypokalemia occurred in 10% vs 0.8% and 1% vs 0.2%. Serious adverse events occurred in 28% vs 24%. Adverse events led to dose modification or interruption in 32% vs 17% and to treatment discontinuation in 12% vs 10%. Adverse events led to death in 5% vs 4%.
The investigators concluded: “The addition of abiraterone acetate and prednisone to androgen-deprivation therapy significantly increased overall survival and radiographic progression-free survival in men with newly diagnosed, metastatic, castration-sensitive prostate cancer.”
The study was funded by Janssen Research and Development.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
