Ra-223: New Arrow in Prostate Cancer Quiver

Howard I. Scher, MD; Johann S. de Bono, MD


June 10, 2013

In This Article

Novel Immunoconjugates and Combinations

Dr. de Bono: It's a concern. Ian Tannock[10] today presented the data with docetaxel and aflibercept. It was another negative study with docetaxel. It was a tubulin-binding drug that has, like cabazitaxel (another tubulin-binding drug) given benefit to our patients. The question now is, should we pursue any further docetaxel combinations? My concern would be Ra-223, but that would not be my primary choice of combination. The novel tubulin-binding immunoconjugates were interesting at this meeting. What do you think of those?

Dr. Scher: We worked with some of the first-generation prostate-specific membrane-antigen (PSMA)-targeting agents, where the actual linker between the cytotoxic agent and the antibody was not stable. We saw the more traditional toxicities, with some antitumor effects. More recently, Daniel Danila[11] has been leading a program developing a six-transmembrane epithelial antigen of the prostate (STEAP) antibody drug conjugate. We have reached the point now where we are seeing significant responses. It has been particularly interesting that we have the ability to image with a PET tracer to STEAP. We are in the process of exploring the expression across multiple lesions, and whether there are high and low expressers within the same patient. We also want to see whether we can associate the uptake with the tracer with the response to the conjugate. This is turning out to be a very important and fruitful area of development, particularly as the DM1 conjugate to HER2 was recently shown to prolong life. Have you worked with these agents?

Dr. de Bono: Yes. We published in Journal of Clinical Oncology,[12] from my time in San Antonio, [a study of] one of the very first immunoconjugates, called cantuzumab. The initial linkers from Seattle Genetics have been improved. We saw some neuropathy initially with those agents, because of the maytansinoid release. The more novel conjugates look particularly promising. I’m quite excited about those. In fact, there is going to be quite a lot of work in this space with lots of new agents.

Dr. Scher: I share your enthusiasm. This has been an amazing 3 years. We are looking forward to the readout of some of the biologic trials because we have already seen one that has been approved, sipuleucel-T, which has been shown to prolong life. The ipilimumab trial is on the way, as are other programs. Certainly with cabozantinib, a very exciting compound, we were involved shortly after some of the initial findings of the bone scan improvement, which was unparalleled, plus the pain relief was quite dramatic. The 2 trials will hopefully read out soon. We have seen tremendous unprecedented progress in the past 3 years. We hope that this will continue. Most important is that we are not only understanding the biology more but we are learning the context in which to apply the biology and have the tools to characterize the disease much more completely than we could ever do. This will make a difference for our patients, even more than in the past 3 years.

Dr. de Bono: Thank you.

Dr. Scher: Thank you for joining us for this edition of Medscape Oncology Insights. This is Howard Scher, reporting from ASCO 2013.


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