Chicago, IL—The results from 2 studies should advance the use of abiraterone acetate (Zytiga) to the frontline treatment of patients with hormone-sensitive advanced prostate cancer, effectively replacing chemotherapy, said several experts at the ASCO 2017 annual meeting.
Adding abiraterone to standard initial treatment that includes androgen-deprivation therapy (ADT) increased survival and reduced mortality risk by 37% over 3 years versus standard of care in the STAMPEDE clinical trial of men with locally advanced or metastatic prostate cancer.
In the LATITUDE study, men with high-risk metastatic prostate cancer who received abiraterone plus ADT and prednisolone had a 38% reduction in mortality risk, with a median follow-up of 2 to 2.5 years, compared with ADT plus placebo.
“Several years ago, the STAMPEDE trial actually showed benefit associated with chemotherapy added to conventional hormone therapy for metastatic prostate cancer. Here, the same study backbone is used to show the benefit of abiraterone,” said ASCO expert Sumanta K. Pal, MD, Co-Director, Kidney Cancer Program, City of Hope, Duarte, CA. “Abiraterone should change the treatment paradigm for patients with newly diagnosed metastatic prostate cancer and largely displace chemotherapy from the current paradigm.”
The STAMPEDE Clinical Trial
In the STAMPEDE study, 1917 men with high-risk prostate cancer were randomized to ADT plus abiraterone 1000 mg daily and prednisolone 5 mg daily, or the standard of care with ADT and radiation therapy. Standard therapy involved ADT for ≥2 years; radiation therapy was also mandated for men with node-negative, nonmetastatic disease and encouraged for those with node-positive, nonmetastatic disease.
The 3-year overall survival (OS) rate was 76% in men who received standard therapy compared with 83% in men who received standard therapy plus abiraterone and prednisolone (hazard ratio [HR], 0.63; P = .0012).
“Our projections are that in the experimental arm, in the metastatic part of the comparison, the median survival will be around 3.5 years in our population to 6.5 years for the abiraterone [arm], so we think this is one of the biggest survival gains ever reported in a trial of an adult solid tumor,” said lead investigator Nicholas D. James, PhD, BSc, MBBS, FRCP, FRCR, Professor of Clinical Oncology, Queen Elizabeth Hospital Birmingham, United Kingdom.
The effect of adding abiraterone and prednisolone to standard therapy on OS was similar in men with metastatic or nonmetastatic disease. “We think these survival data apply to the whole trial population, not just to the metastatic subpopulation,” said Dr James.
The rates of failure-free survival at 3 years were 75% with abiraterone plus prednisolone and standard therapy versus 45% with standard therapy, corresponding to a 71% relative improvement in risk with abiraterone (HR, 0.29; P = .377 × 10–61). The relative risk for skeletal-related outcomes was also reduced by 55% in the abiraterone group.
These findings should prompt a change in the upfront care of patients with newly diagnosed advanced prostate cancer to include abiraterone, said Dr James.
The LATITUDE Clinical Trial
In the LATITUDE clinical trial, 1199 men with newly diagnosed, high-risk, metastatic prostate cancer who had not previously received ADT were randomized to receive ADT plus abiraterone and prednisone or ADT plus placebo. At a median follow-up of 30.4 months, the median OS had not yet been reached in the abiraterone group versus 34.7 months in the placebo group, for a 38% reduction in the risk for death, favoring abiraterone (P <.0001), reported Karim Fizazi, MD, PhD, Head, Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France.
Abiraterone plus prednisone and ADT was also associated with a 53% reduction in the risk for radiographic progression-free survival compared with ADT plus placebo (33.0 months vs 14.8 months, respectively; P <.0001).
“These important findings will very likely change the standard of care of patients who have evidence of metastatic disease at the time of prostate cancer diagnosis,” said Dr Fizazi.
Adverse events with abiraterone therapy in both clinical trials were predominantly cardiovascular-related, including hypertension, which was approximately twice more common in the abiraterone groups than in the control groups. Liver enzyme abnormalities were also more common in the abiraterone groups than in the control groups.