PARP inhibition, TMPRSS2-EPG gene fusion, and veliparib in mCRPC


A Phase II clinical trial being coordinated by researchers at the University of Michigan Cancer Center is (as far as we know) the first trial ever to explore the potential of treatment for men with metastatic, castration-resistant prostate cancer (mCRPC) who carry the TMPRSS2-EPG fusion gene (as opposed to those who do not).

According to a recent article in the ASCO Post and related information on the ClinicalTrials.gov web site, eligible patients with mCRPC can enroll in this trial at about a dozen different centers around the country. All eligible patients will need to undergo a biopsy to remove tissue from a site of metastatic disease (i.e., not a prostate biopsy) so that the investigators can determine whether or not each patient carries the TMPRSS2-EPG fusion gene, which is believed to be important in the progression of at least some types of advanced prostate cancer. (It is currently believed that about half the men with metastatic prostate cancer carry this particular gene).

All eligible patients will initially receive treatment with abiraterone acetate + prednisone. They will then be randomized (and stratified on the basis of whether or not they are positive for the TMPRSS2-EPG fusion gene) to receive and investigational drug known as veliparib or no additional therapy.

Veliparib — which until recently was simply known by the code number ABT-888 — is a so-called PARP inbibitor (a drug that inhibits the activity of an enzyme known as poly ADP ribose polymerase. You can find details about how this type of drug works on the Wikipedia web site. PARP inhibitors are being investigated in  the treatment of a wide range of diseases, but there is significant evidence that they may be beneficial in the management of progressive forms of prostate cancer.

Not only is this trial the first to investigate the potential of the investigational drug veliparib in the treatment of this subset of men with mCRPC, it is also the first trial that we are aware of to explore the potential of drug therapy in any genetic subset of prostate cancer. From that persepctive this is an important clinical trial that may help us to understand why some men respond better than others to differing types of treatment for mCRPC in particular and advanced forms of prostate cancer more generally. We strongly encourage men diagnosed with mCRPC (and particularly those who are newly diagnosed and therefore who have not had prior treatment for mCRPC) to consider enrolling in this trial. The dozen or so centers involved include several major centers around the country.

2 Responses

  1. Isn’t this trial with another PARP inhibitor very similar (PARP inhibitor to treat genetic subset?)

  2. Dear Doug:

    Well … sorta, but not really (in my opinion). The trial you refer to was one in which a whole bunch of patients (all of whom carried the BRCA 1/2 genes, but who had all sorts of different types of advanced cancer) were treated with olaparib in the hope that it might show signs of activity. Eight of those men had advanced prostate cancer and olaparib showed activity in some of them (but we don’t know much more than that). By contast, in the new trial, the investigators are actually randomizing patients to treatment with or without ABT-888 with the specific intent of discovering whether this drug is more effective and still safe (in combination with abiraterone acetate + prednisone) in the treatment of men who carry the fusion gene by comparison with the men who don’t. This is therefore a very different type of trial that is specific to prostate cancer. (Some might argue that I am splitting hairs, but I really don’t think I am at all.)

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