The European Commission has approved abiraterone acetate (Zytiga) in combination with prednisone/prednisolone for the treatment of adult men with newly-diagnosed high-risk metastatic hormone-sensitive prostate cancer.
Karim Fizazi, MD, PhD
The European Commission (EC) has approved abiraterone acetate (Zytiga) in combination with prednisone/prednisolone for the treatment of adult men with newly-diagnosed high-risk metastatic hormone-sensitive prostate cancer (mHSPC) in combination with androgen deprivation therapy (ADT).
Janssen Biotech announced the commission’s decision in a press release. This move by the EC follows a recommendation issued in October from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) supporting the use of abiraterone acetate in this setting.
The approval is based on results from the phase III LATITUDE trial showing that abiraterone combined with prednisone/prednisolone and ADT reduced the risk of death by 38% compared with ADT and placebo in men with high-risk, metastatic castration-sensitive prostate cancer.1,2 The median overall (OS) survival was not reached with abiraterone acetate versus 34.7 months with placebo (hazard ratio [HR], 0.62; 95% CI, 0.51-0.76; P <.001).
“Prostate cancer is the most common form of cancer in men throughout Europe and today’s decision helps to fill a critical medical need for these patients,” Karim Fizazi, MD, PhD, principal investigator of the LATITUDE trial and head of medical oncology at Institute Gustave Roussy, France, said in a sattement. “We hope to significantly improve the lives of many men across Europe living with this disease and the approval of this treatment in an earlier stage of prostate cancer helps address this.”
In LATITUDE, 1199 newly diagnosed patients with high-risk metastatic prostate cancer were randomly assigned to abiraterone acetate, prednisone, and ADT (n = 597) or ADT and placebo (n = 602). Patients received 1000 mg abiraterone acetate and 5 mg prednisone daily.
Eligible patients had not previously received ADT therapy and had at least 2 of 3 risk factors: Gleason score greater than or equal to 8, measurable visceral metastases, or 3 or more bone lesions. Men in the study had either a positive bone scan or a metastatic lesion at the time of diagnosis on CT or MRI.
The radiographic progression-free survival with abiraterone acetate was 33.0 months compared with 14.8 months for ADT alone, representing a 53% reduction in the risk of progression or death (HR, 0.47; 95% CI, 0.39-0.55; P <.001). The OS rate at 3 years was 66% in the abiraterone acetate group versus 49% with ADT.
The time to pain progression was also reduced by 31% with abiraterone acetate versus ADT (HR, 0.70; 95% CI, 0.58-0.83; P <.0001). Additionally, the risk of developing a skeletal-related event was 30% lower with abiraterone acetate versus ADT (HR, 0.703; 95% CI, 0.539-0.916; P = .0086). The risk of starting chemotherapy was reduced by 56% with abiraterone acetate versus ADT alone (HR, 0.443; 95% CI, 0.349-0.561; P <.0001).
The most common grade 3/4 adverse events with abiraterone acetate versus placebo, respectively, were hypertension (20.3% vs 10.0%); hypokalemia (10.4% vs 1.3%); elevated alanine aminotransferase (5.5% vs 1.3%), and elevated aspartate aminotransferase (4.4% vs 1.5%).
Abiraterone acetate was first approved by the EC in 2011 in combination with prednisone for the treatment of men with metastatic castration-resistant prostate cancer following chemotherapy. It has since gained approval earlier in the treatment paradigm for use prior to chemotherapy.
“This EC approval is a major step forward for men living with prostate cancer across Europe and offers patients with newly diagnosed high-risk metastatic hormone-sensitive prostate cancer a new treatment option,” Ivo Winiger-Candolfi, MD, oncology solid tumor therapy area lead, Janssen Europe, Middle East and Africa, said in a statement. “We are encouraged by the data we have seen to date and remain committed to transforming outcomes for prostate cancer patients.”