FDA Approval Sought for Abiraterone Acetate for Early-Stage Metastatic Prostate Cancer

A supplemental new drug application has been submitted for abiraterone acetate in combination with prednisone and androgen deprivation therapy for high-risk men with castration-sensitive metastatic prostate cancer.

Craig Tendler, MD

A supplemental new drug application has been submitted for abiraterone acetate (Zytiga) in combination with prednisone and androgen deprivation therapy (ADT) for high-risk patients with metastatic hormone-naïve prostate cancer (HNPC) or newly-diagnosed metastatic hormone-sensitive prostate cancer (HSPC), according to a statement from the company developing therapy, Janssen Biotech.

UPDATE 2/8/2018: FDA Approves Abiraterone for High-Risk Prostate Cancer

The application was based on findings from the phase III LATITUDE trial,1,2 which demonstrated superior overall survival (OS) with abiraterone acetate, prednisone, and ADT compared with ADT and placebo for patients with high-risk metastatic, castration-sensitive prostate cancer. In the study, the addition of abiraterone acetate to ADT reduced the risk of death by 38% compared with ADT and placebo. The median OS was not reached with abiraterone acetate versus 34.7 months with placebo (HR, 0.62; 95% CI, 0.51-0.76; P <.001).

“We are excited about the promising results from the LATITUDE study which suggest that Zytiga can benefit men with newly diagnosed, high-risk metastatic prostate cancer, rather than waiting for them to become resistant to conventional hormonal treatments,” Craig Tendler, MD, vice president, Late-Stage Development and Global Medical Affairs for Oncology, Hematology and Supportive Care at Janssen, the developer of abiraterone acetate, said in a statement. “We look forward to working with the FDA on the review of this application to provide a new therapeutic option for men with newly diagnosed, high-risk metastatic prostate cancer.”

The LATITUDE trial randomized 1199 newly diagnosed patients with high-risk metastatic prostate cancer to abiraterone acetate, prednisone, and ADT (n = 597) or ADT and placebo (n = 602). Abiraterone acetate was administered at 1000 mg daily and prednisone was given at 5 mg daily. Patients had either a positive bone scan or a metastatic lesion at the time of diagnosis on CT or MRI. 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.

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, 0.695; 95% CI, 0.583-0.829; 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%).

In a further analysis of patient-reported outcomes,3 there was a delay in degradation of health-related quality of life with abiraterone acetate versus ADT alone (HR, 0.853; 95% CI, 0.736-0.989; P = .0322). Moreover, the time to worst fatigue intensity progression was delayed by 35% (HR, 0.652; 95% CI, 0.527-0.805; P = .0001).

“In combination with the significant benefits in survival and disease progression, the new data from the LATITUDE clinical trial suggests that abiraterone acetate plus prednisone, in combination with androgen deprivation therapy, offers a much-needed efficacious treatment option for patients with newly-diagnosed metastatic disease,” Principal Investigator Karim Fizazi, MD, Head of the Medical Oncology Department at Institute Gustave Roussy, France, said in a statement.

Abiraterone acetate 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.


  1. Fizazi K, Tran N, Fein LE, et al. the LATITUDE investigators. LATITUDE: A phase 3 double-blind, randomized trial of androgen deprivation therapy (ADT) with abiraterone acetate (AA) plus prednisone (P) or placebos (PBOs) in newly diagnosed high-risk metastatic hormone-naïve prostate cancer (mHNPC) patients (pts). J Clin Oncol. 2017;35 (suppl; abstr LBA3).
  2. Fizazi K, Tran N, Fein LE, et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2017;377:352-360.
  3. Chi K, Protheroe A, Rodrigues Antolin A, et al. Benefits of Abiraterone Acetate Plus Prednisone (AA+P) When Added to Androgen Deprivation Therapy (ADT) in LATITUDE on Patient (Pt) Reported Outcomes (PRO). Presented at: 2017 ESMO Congress; Madrid, Spain; September 8-12, 2017. Abstract 783O.