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Biomarkers, Combo Regimens Key to Mitigating AR-Resistance in mCRPC

Gina Columbus @ginacolumbusonc
Published: Monday, Nov 21, 2016

When we speak to patients, we need to be clear about not just the options we have available now, but the options we have coming in the future. That all comes back to overcoming resistance: combinations, identifying biomarkers, and new drugs that are on the horizon.

What are some of these other novel agents?

You might imagine that targeting the N-terminal of the AR may have activity. There are drugs that may have activity against the AR-V7 splice variant through different mechanisms. In terms of the AR family, there is more to be done.

Is it beneficial to look at immunotherapy in this subset?

It’s a great time to look at immunotherapy. It works in every other disease; it has got to work [in prostate cancer]. There was actually a recent study presented by Dr Julie Graff at the 2016 ESMO Congress. She looked at patients who were progressing on enzalutamide and then she continued enzalutamide and added a PD-L1 antibody.

The responses were quite dramatic; there were 5 exceptional responders. They had very high PSA levels—1 patient had a PSA of 2000—and already received enzalutamide and progressed. She added the PD-L1 antibody and she saw that the PSA became undetectable. Not only that, but 2 patients had disease in the liver that regressed; they had a partial response. We are getting there, we are getting closer, and we should not give up on immunotherapy in advanced disease.

Looking ahead, what do you hope is accomplished here within 5 years?

If you think back to what has happened in the last 5 years, we didn’t have any AR-targeted therapies for mCRPC that were approved. The sky is the limit. I would like to see combinations come to fruition because there are very few diseases where monotherapy alone works. Combinations are an important field, biomarkers will be key in understanding and mitigating resistance, as well as choosing and selecting drugs based on genomic profiling. Not in 5 years, but I expect in 1 year, things are going to change dramatically.
Graff JN, Alumkal JJ, Drake CG, et al. First evidence of significant clinical activity of PD-1 inhibitors in metastatic, castration resistant prostate cancer (mCRPC). Presented at: 2016 ESMO Congress; October 7-11, 2016; Copenhagen, Denmark. Abstract 719O.

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