The FDA approved Abiraterone acetate (Zytiga) plus prednisone because it demonstrated a survival benefit for men with metastatic castrate resistant prostate cancer (mCRPC) in the pre-chemotherapy setting.  Given the newness of the approval of Zytiga in this disease stage there is a lack of data on how Zytiga affects the efficacy of enzalutamide (Xtandi) or chemotherapy (docetaxel) when given after Zytiga.

In a study performed at Duke Cancer Institute men who received Zytiga prior to chemotherapy, either on trial or as their treatment, who had also complete follow up on response to subsequent therapy as of the cutoff date, August 12, 2013, were included in this study. The researchers included clinical and demographic information, laboratory values, response, and progression and overall survival-based outcomes.

The men were separated into two groups: group A, who were treated with Zytiga followed by Xtandi, and group B, who were treated with Zytiga followed by chemotherapy. The primary objective of the study was to describe the responses and progression free survival experienced by the men to subsequent therapy after progression (failure) to the Zytiga.

The researchers found thatGroup A, which consisted of a sample size of 8 men (Zytiga followed by Xtandi) and group B, which consisted of a sample size of 12 men (Zytiga followed by chemotherapy) had similar clinical characteristics at the point that the Zytiga failed.  This included disease progression and pain.

They also found that the men assigned to group A had higher baseline circulating tumor cells (CTC) and a higher prostate specific antigen (PSA) level. Group B was younger (mean 65 vs 73 yrs).

Median progression free survival (PFS) for group A was 3.6 months, and median overall survival (OS) was 8.5 months. Median PFS for group B was 5.1 months, and median OS was not reached.

A ?50% PSA decline was achieved in 12.5% of men in group A vs 50% of the men in group B. The radiographic progression response was 62.5% of men in group A and 33% of men in group B.

The data in this small study suggests that there is a very clear cross-resistance after Zytiga in the majority of men with mCRPC.  Chemotherapy provided a greater probability of a PSA decline and radiographic/clinical benefit.

Due to the very small sample sizes in this study and the very significant implications of the results, especially in light of the high probability of the FDA approving Xtandi along with Zytiga in the pre-chemotherapy stage, we must see additional explorations of this question.

J Clin Oncol 32, 2014 (suppl; abstr e16031); 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.