CHICAGO—Adding abiraterone to androgen-deprivation therapy (ADT) as first-line treatment for advanced or high-risk prostate cancer (PCa) improves survival and delays disease progression compared with ADT alone, according to the findings of separate studies presented at the American Society of Clinical Oncology (ASCO) Annual Meeting and published concurrently in the New England Journal of Medicine.
As a result of study findings, combined therapy with abiraterone and ADT in this population is or might be considered a new standard of care, according to researchers.
In the randomized double-blind phase 3 LATITUDE trial, which included 1199 patients with newly diagnosed metastatic hormone-naïve prostate cancer (mHNPC), investigators led by Karim Fizazi, MD, PhD, head of the Department of Cancer Medicine at Gustave Roussy, University Paris-Sud in Villejuif, France, found patients who received abiraterone and prednisone in addition to ADT had a 38% decreased risk of death and 53% decreased risk of radiographic progression compared with those who received placebo and ADT.
The median length of radiographic progression-free survival was 33.0 months in the abiraterone arm compared with 14.8 months in among the placebo recipients.
The independent data and safety monitoring committee overseeing the study unanimously recommended that the trial be unblinded and patients in the placebo arm be allowed to receive abiraterone.
The treatment arms had similar numbers of patients who experienced serious adverse events, but the abiraterone arm had higher rates of grade 3 hypertension and hypokalemia, the investigators reported.
“Given these findings, I believe that the addition of abiraterone to androgen deprivation therapy can be considered as a new standard of care for men with high-risk de novo metastatic prostate cancer,” Dr Fizazi told meeting attendees.
The study included 597 and 602 men randomly assigned to received abiraterone/prednisone or placebo, respectively, in addition to ADT. During a median follow-up time of 30.4 months, 406 deaths and 593 radiographic progression events occurred.
The men in the study received their diagnosis of mHNPC 3 months or less before randomization. To be included in the trial, they needed to have least 2 of 3 risk factors: a Gleason score of 8 or higher, 3 or more bone metastases, or 3 or more visceral metastases.
The other study, the STAMPEDE trial, found that, compared with ADT alone, upfront use of a combination of abiraterone/prednisolone and ADT in hormone-naïve PCa patients was associated with a significant 37% improvement in overall survival, 71% improvement in failure-free survival, and 55% reduction in symptomatic skeletal-related events, said lead investigator Nicholas D. James, MBBS, PhD, of the University of Birmingham in the UK. The treatment was well tolerated, with toxicities similar those observed with the use of abiraterone in men with castration-resistant PCa.
“So our opinion is that abiraterone acetate and prednisolone should be part of the standard of care for men starting long-term androgen deprivation,” Dr James told colleagues.
The trial enrolled patients with newly diagnosed prostate cancer that was metastatic, node-positive, or high risk locally advanced disease, or PCa previously treated with radical surgery or radiotherapy and was now relapsing with high-risk features. The study population included 1917 patients randomly assigned to receive ADT alone (957 patients) or the combination therapy (960 patients). During a median follow-up of 40 months, 262 men in the ADT-alone arm and 184 in the combination arm died.
1. Fizazi K, Tran N, Fein LE, et al. LATITUDE: A phase III, double-blind, randomized trial of androgen deprivation therapy with abiraterone acetate plus prednisone or placebos in newly diagnosed high-risk metastatic hormone-naïve prostate cancer. J Clin Oncol 2017;35 (suppl; abstr LBA3). Data presented at the 2017 American Society of Clinical Oncology Annual Meeting in Chicago on June 4. Published online in the New England Journal of Medicine on June 4, 2017.
2. James ND, de Bono JS, Spears MR, et al. Abiraterone for prostate cancer not previously treated with hormone therapy. J Clin Oncol 2017;35 (suppl LBA5003). Data presented at the 2017 American Society of Clinical Oncology Annual Meeting in Chicago on June 3. Published online in the New England Journal of Medicine on June 3, 2017.