FDA Approves Zytiga for High-Risk Prostate Cancer

Janssen Biotech announced that the Food and Drug Administration has approved Zytiga (abiraterone acetate) in combination with prednisone for high-risk castration-sensitive prostate cancer.

The approval was based at findings from the phase 3 LATITUDE trial in which there was a 38 percent reduction in the risk of death with the addition of Zytiga and prednisone to ADT compared with ADT alone. After a median follow-up of 30.4 months, median overall survival (OS) was not yet reached with Zytiga versus 34.7 months with placebo for patients with high-risk metastatic, castration-sensitive prostate cancer.

“LATITUDE was a large global trial which produced impressive and clinically significant results in overall survival,” lead investigator of the study Karim Fizazi, M.D., Ph.D., Head of the Medical Oncology Department at Institute Gustave Roussy, Villejuif, France, said in a statement. “With today’s approval, abiraterone acetate plus prednisone could become a standard of care for patients with metastatic high-risk castration-sensitive prostate cancer.”

In the LATITUDE trial, 1,199 newly diagnosed patients with high-risk metastatic prostate cancer were randomized to Zytiga, prednisone, and ADT or ADT and placebo. Patients had not received prior ADT and had at least two of three risk factors: a Gleason score (a grading system that rates prostate cancer severity) greater of eight or more, measurable visceral metastases or three or more bone lesions.

In each group, approximately 20 percent of patients were 75 years of age or older, with a median age around 68 years. The Gleason score at diagnosis was eight or greater for nearly all men enrolled (98 percent) and nearly all enrolled had three or more sites of bone metastases (98 percent). The baseline pain score was four or more for just over a quarter of men in the trial, and the majority had a pain score of zero or one (50 percent).

The median radiographic progression-free survival with Zytiga was 33 months compared with 14.8 months for ADT alone, representing a 53 percent reduction in the risk of progression or death. The OS rate at three years was 66 percent in the Zytiga group versus 49 percent with ADT.

The time to pain progression was reduced by 31 percent with Zytiga versus ADT. Additionally, the risk of developing a skeletal-related event was 30 percent lower with Zytiga versus ADT. The risk of starting chemotherapy was reduced by 56 percent with Zytiga versus ADT alone.

Overall, 63 percent of men in the Zytiga group experienced a grade 3/4 adverse event (AE) compared with 48 percent of those in the placebo arm. The most common grade 3/4 AEs with Zytiga versus placebo, respectively, were hypertension; hypokalemia ; elevated alanine aminotransferase, and elevated aspartate aminotransferase.

Serious AEs were experienced by 28 percent versus 24 percent of men in the Zytiga group and placebo arm, respectively. AEs led to treatment discontinuation for 12 percent of men in the investigational group versus 10 percent in the placebo arm, and AEs led to death for five percent and four percent of men, respectively.

In a further analysis of patient-reported outcomes, there was a delay in degradation of health-related quality of life (HrQOL) with Zytiga versus ADT alone. This equated to a 15 percent reduction in the risk of HrQOL degradation with the addition of Zytiga. Moreover, the time to worst fatigue intensity progression was delayed by 35 percent.

“Today’s approval marks an important step in addressing the unmet needs of patients with metastatic high-risk castration-sensitive prostate cancer by providing an option that has demonstrated improvement in overall survival,” Andree Amelsberg, M.D., vice president of Oncology Medical Affairs at Janssen Biotech, Inc., part of the Janssen Pharmaceutical Companies of Johnson & Johnson, said in a statement. “This milestone is an exciting turning point for researchers and clinicians, and most importantly, for patients suffering from this disease and their families who now have an important additional therapeutic option.”

Zytiga was first approved 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.