Combined therapy with abiraterone acetate/prednisone plus androgen deprivation therapy (ADT) significantly improved overall survival and radiographic progression-free survival (PFS) among men with metastatic hormone-naive prostate cancer compared with ADT and placebo alone, according to the results of the phase III LATITUDE trial (abstract LBA3) presented at the 2017 ASCO Annual Meeting.
“In my opinion, these findings support the fact that adding abiraterone and prednisone to castration should now be considered the new standard of care for men with newly diagnosed metastatic prostate cancer,” said researcher Karim Fizazi, MD, PhD, head of the department of cancer medicine at Gustave Roussy, University Paris-Sud, Villejuif, France.
Historically, ADT has been the standard of care for patients with metastatic prostate cancer. However, at approximately 1 year on ADT about one-half of patients with metastatic disease have progressed. More recently, ADT plus docetaxel has been the new standard of care.
In LATITUDE, the researchers tested adding abiraterone plus prednisone to ADT. Abiraterone was already an approved agent for castration-resistant disease, and is associated with improved overall survival in this setting.
The trial included 1,199 men with newly diagnosed metastatic hormone-naive prostate cancer and randomly assigned them to ADT plus abiraterone/prednisone or ADT plus placebo. All patients in the trial had at least two of three risk factors: Gleason score of 8 or more, 3 or more bone metastases, or 3 or more visceral metastases. The co-primary endpoints were overall survival and radiographic PFS.
With a median follow-up of 30.4 months, men assigned to abiraterone/prednisone plus ADT had a significant improvement in overall survival compared with ADT alone. There was a 38% decreased risk for death with abiraterone (95% CI, 0.51-0.76; P = .0001). Median overall survival has not yet been reached for abiraterone and was 34.7 months in the placebo group. The overall survival rate at 3 years was 66% for abiraterone compared with 49% for the control arm.
Abiraterone was also associated with a 53% lower risk for cancer progression (hazard ratio, 0.47; 95% CI, 0.39-0.55; P = .0001) and resulted in cancer growth being delayed by a median of 18.2 months. The median PFS was 33.0 months for abiraterone compared with 14.8 months for the control arm.
According to Dr. Fizazi, all secondary endpoints for the trial were met, including improvements in time to prostate-specific antigen progression, time to pain progression, and time to next symptomatic skeletal event. The safety profile was similar to that seen in other trials of abiraterone with the most common adverse events being hypertension, hypokalemia, increase ALT or AST, and a slight increase in cardiac disorders.
Commenting on the study, ASCO Expert Sumanta Kumar Pal, MD, pointed out that at the 2014 ASCO Annual Meeting the treatment paradigm for these patients was changed with the results of the NCI-sponsored study CHARTED, which showed a survival benefit associated with the addition of chemotherapy to hormone therapy in this setting.
“The data from Dr. Fizazi provides an important alternative to chemotherapy, mainly the use of the agent abiraterone. Abiraterone inhibits testosterone production more potently than hormone therapies previously used in this setting,” Pal said. “Although it is challenging to put the existing data for chemotherapy and abiraterone side by side, at first glance it appears as though the benefit and survival seen with abiraterone mirrors or exceeds the benefit we have seen with chemotherapy…These data should immediately re-shape our treatment algorithms for prostate cancer, and abiraterone with conventional hormone therapy should be considered the new standard of care for men with high-risk prostate cancer.”