Abiraterone acetate (AA) or Zytiga has demonstrated a survival benefit in the pre-chemotherapy setting for men with advanced prostate cancer that has become castrate resistant (mCRPC). As a result it is in widespread clinical use in the United States prior to the use of chemotherapy with docetaxel. Since its FDA approval post chemotherapy there has developed increasing interest in utilizing enzalutamide (Xtandi) in this same space, prior to chemotherapy.
However, there remains a lack of data on what might be the impact of therapy with Zytiga have on the efficacy of Xtandi or docetaxel if later given. Considering that Xtandi will probably also receive FDA approval in this prechemotherapy space as well as the developing trend to use it off lable in this space there is a very real need to know this information.
Researchers at Duke University looked at this issue. They took a sampling of men with mCRPC treated Zytiga prior to chemotherapy or Xtandi, either on a trial or in standard practice. Clinical and demographic information, laboratory values, response, and progression and overall survival-based outcomes were also abstracted.
The men were separated into two main groups: group A, who were treated with Zytiga followed by Xtandi and group B, who were treated with Zytiga followed by docetaxel-based chemotherapy.
The primary objective was to describe response and progression free survival to subsequent therapy after progression on Zytiga.
Group A (Zytiga then Xtandi, n=8), and group B (Zytiga then docetaxel, n=12) had similar clinical characteristics at progression, including pain and patterns of spread. However, group A had higher baseline circulating tumor cell (CTC) and prostate specific antigen (PSA) levels then , group B, who were younger (mean 65 vs 73 yrs).
The research found a clear cross-resistance in the majority of men with mCRPC, while docetaxel provided a greater probability of PSA decline and radiographic/clinical benefit then the Xtandi group after Zytiga exposure. If you have had Zytiga discuss with your doctor the possible advantage of next using chemotherapy as opposed to Xtandi.
These data may help to inform on the complex treatment decisions facing men with mCRPC progressing on first line Zytiga and should be explored in larger multicenter registries and controlled trials.
J Clin Oncol 32, 2014:Tian Zhang, Mallika S. Dhawan, Patrick Healy, Daniel J. George, Jorge Oldan, Bennett Chin, Andrew J. Armstrong
Joel T Nowak, M.A., M.S.W.