What is the future potential of abiraterone acetate?
Posted Jan 24 2011 12:00am
An article by Mohler and Pantuck , published on line last week in the Journal of Urology, provides two perspectives on the future potential of abiraterone acetate in the treatment of prostate cancer.
The article which is framed as a pro/con debate focuses largely on the impact of abiraterone acetate on the control of the underlying biochemical mechanisms of castration-resistant prostate cancer (CRPC). However, looked at from a patient perpective, this intellectual scientific question is really of rather less importance than future data from well-designed, well-executed clinical trials.
It is true that we know a good deal more now about the roles of androgens and the androgen receptor in CRPC than we did 10 years ago. This has led to a growing stream of new therapies being tested for effectiveness and safety in the treatment of CFRPC and metastatic CRPC over the past 3 years. Abiraterone acetate is just the first of this potential flood of products. Others following close on its heels include MDV3100, TAK-700, VN124-1, and more are still to come.
We have already seen that abiraterone acetate + prednisone can extend overall survival by 4.4 months compared to a placebo + prednisone in men with metastatic CRPC who have progressed after treatment with docetaxel-based chemotherapy but who continue to receive standard hormone therapy with an LHRH agonist. A second Phase III trial should soon provide data on the use of abiraterone + prednisone in men with chemotherapy-naïve, metastatic prostate cancer. From this point on, however, things are going to become a lot more difficult.
What if any is the potential role for abiraterone earlier in the disease state? At this time we simply don’t know. It is perfectly possible that using abiraterone earlier may actually be disasterous because of effects it may have in long-term use on the peripheral androgen pathways. On the other hand, maybe men with advanced disease can be alternately treated on intermittent therapy with standard hormone therapy and abiraterone acetate + prednisone and gain a significant survival benefit compared to intermittent hormone therapy followed by abiraterone once standard intermittent hormone therapy has failed. Who knows?
What is very clear is that clinical trials for men with progressive prostate cancer are about to become a great deal more complicated. We will no longer be living in a world where a new product is tested against a placebo. As of now we are going to start to see the type of complex multi-drug clinical trials that have been customary in some other forms of cancer for many years. Acronyms like BLAP (bicalutamide + leuprolide + abiraterone + prednisone) and alt-BLAP (alternating bicalutamide + leuprolide with abiraterone + prednisone) are in our future. And what is going to be extremely important will be to watch how men react to some of these therapies over time, not just in the short term.
An article by Mohler and Pantuck , published on line last week in the Journal of Urology, provides two perspectives on the future potential of abiraterone acetate in the treatment of prostate cancer.
The article which is framed as a pro/con debate focuses largely on the impact of abiraterone acetate on the control of the underlying biochemical mechanisms of castration-resistant prostate cancer (CRPC). However, looked at from a patient perpective, this intellectual scientific question is really of rather less importance than future data from well-designed, well-executed clinical trials.
It is true that we know a good deal more now about the roles of androgens and the androgen receptor in CRPC than we did 10 years ago. This has led to a growing stream of new therapies being tested for effectiveness and safety in the treatment of CFRPC and metastatic CRPC over the past 3 years. Abiraterone acetate is just the first of this potential flood of products. Others following close on its heels include MDV3100, TAK-700, VN124-1, and more are still to come.
We have already seen that abiraterone acetate + prednisone can extend overall survival by 4.4 months compared to a placebo + prednisone in men with metastatic CRPC who have progressed after treatment with docetaxel-based chemotherapy but who continue to receive standard hormone therapy with an LHRH agonist. A second Phase III trial should soon provide data on the use of abiraterone + prednisone in men with chemotherapy-naïve, metastatic prostate cancer. From this point on, however, things are going to become a lot more difficult.
What if any is the potential role for abiraterone earlier in the disease state? At this time we simply don’t know. It is perfectly possible that using abiraterone earlier may actually be disasterous because of effects it may have in long-term use on the peripheral androgen pathways. On the other hand, maybe men with advanced disease can be alternately treated on intermittent therapy with standard hormone therapy and abiraterone acetate + prednisone and gain a significant survival benefit compared to intermittent hormone therapy followed by abiraterone once standard intermittent hormone therapy has failed. Who knows?
What is very clear is that clinical trials for men with progressive prostate cancer are about to become a great deal more complicated. We will no longer be living in a world where a new product is tested against a placebo. As of now we are going to start to see the type of complex multi-drug clinical trials that have been customary in some other forms of cancer for many years. Acronyms like BLAP (bicalutamide + leuprolide + abiraterone + prednisone) and alt-BLAP (alternating bicalutamide + leuprolide with abiraterone + prednisone) are in our future. And what is going to be extremely important will be to watch how men react to some of these therapies over time, not just in the short term.