Thomas Flaig, MD
Among patients with metastatic prostate cancer who have a suboptimal response to initial androgen deprivation therapy (ADT), there is a small group who respond to hormone therapy, a recent study reports.
This phase II study evaluated the combination of abiraterone acetate (Zytiga) plus prednisone in this patient population, which historically has a poor prognosis as reflected by a prostate-specific antigen (PSA) level higher than 4.0 ng/mL after 7 months of ADT.
Results showed that among 40 evaluable patients, 5 achieved a PSA level of 0.2 ng/mL or lower (95% CI, 4%-27%). Additionally, 13 men achieved a partial response, with a reduction in PSA between 0.2 ng/mL and 4.0 ng/mL.
Lead investigator Thomas Flaig, MD, says that although this trial did not reach its prescribed level of 6 PSA responses of 0.2 ng/mL or lower, these findings indicated potential for hormonal agents in a traditionally poor-prognosis setting and further testing of upfront use in this patient population is warranted.
“This high-risk group of patients—particularly those who have become hormone refractory and are castration resistant in the traditional setting—do not automatically need to go to chemotherapy. Patients with a lower disease burden or slower PSA kinetics could consider next generation hormonal agents such as abiraterone in that setting.”
In an interview with OncLive,
Flaig, associate professor, Division of Medical Oncology, associate dean for clinical research, University of Colorado School of Medicine, discussed the study of abiraterone acetate in metastatic prostate cancer after hormone induction failure and its impact on future research in this setting.
OncLive: Please provide an overview of your study.
This is a study of abiraterone acetate for metastatic prostate cancer in patients with suboptimal biochemical response to hormone induction. These are patients that have metastatic hormone sensitive disease that started on standard hormone therapy, much like we have been doing for several decades. But these are patients that have a poor initial response to the standard hormone therapy. So, the PSA, which we use to monitor disease response, is still above 4, and that is 6 to 9 months after they started that standard hormone therapy. We often tend to see patients, even if their PSA is very very high from the cancer, but they start standard hormone therapy, fall to a very low level. For any patient who is in the situation of being 6 to 9 months after starting, having a PSA of more than 4, they are in a very poor prognosis category.
In a broad way, this study looked at this very high-risk group of patients that had sort of failed with induction therapy, and we added in abiraterone, a next generation antihormonal agent, to see if we can salvage or get a response with additional, more intense hormone therapy.
What were the significance of the results?
There are a couple of important things about this trial. I think that the significant findings here are that there is group of patients that had very deep, near complete responses after adding in abiraterone. One looks at the waterfall plot for the findings here—there was a broad group of patients who had PSA decline.
I think one of the most important findings is that in this high-risk group of patients, there is still some hormone sensitivity, and there is a group that has very good hormone responses. The alternative treatment for these sort of patients is to use chemotherapy and so forth. In fact, when did this study, there were some people who thought that these patients should go directly go to chemotherapy, that they had failed this initial hormone treatment, and they would not respond to hormones at all. We showed there was a group of patients that were still hormone responsive.
Do you think that this evidence is going to change the use of hormone therapy in prostate cancer?
I think this trial helps us to define what is hormone refractory, what is hormone resistant disease. I think this will lead to additional investigation and understanding. One thing that is important to state is that we said for a positive study, we need 6 of these very deep or near complete responses, and we had 5. By the way that this trial was set up, we did not make that endpoint. But these results show that there is a group of patients that responds pretty well.