Olaparib shows activity in advanced, BRCA1/2-positive prostate cancer

Apparently a drug known as olaparib (a so-called poly-ADP ribose polymerase or PARP inhibitor) has shown significant signs of activity against advanced prostate cancer in men who carry the BRCA1 and BRCA2 genes.

Olaparib was being tested in an open-label, Phase II trial on BRCA1/2 patients with several different types of cancer including (for the first time) some patients with BRCA1/2+ positive cancers other than than breast and ovarian cancer. Among the > 300 patients enrolled into this trial, just eight had heavily pretreated, advanced forms of prostate cancer; among these individuals, however, 4/8 patients (50 percent) showed objective clinical responses to olaparib, with 4/8 patients (50 percent) surviving for > 1 year on treatment.

Information about this study is provided in a media release issued to day by the University of Pennsylvania and in the abstract of a paper by Kaufman et al. to be presented at the upcoming annual meeting of the American Society of Clinical Oncology (ASCO) to be held starting on May 31 in Chicago.

Clearly these are very preliminary data with relevance to a small subset of men with progressive forms of prostate cancer, but they may be of considerable importance to men with BRCA1/2 forms of prostate cancer that are relatively unresponsive to other forms of therapy.

2 Responses

  1. That’s pretty interesting. I was reading an article on PARP inhibitors recently. These work by degrading a cell’s ability to repair damaged DNA. But they are only effective if the cell’s ability to repair damaged DNA is already impaired … they sort of push the already hurting cells over the edge. The researchers know that cancers resulting from certain hereditary gene mutations are susceptible to these drugs. There are also companion diagnostic tests being tested that measure a particular tumor’s cells degree of DNA repair degradation. These tests (in retrospective studies using pre-treatment preserved biopsy tissue) have been really good at predicting which tumors will respond to the PARPs and which will not. Another new class of drugs referred to as the “platinums” work in the same way. I’m not an expert on this, so hopefully I’ve summarized the info accurately.

  2. Hello Sitemaster and Doug,

    Thanks for your comments.

    I was also impressed that an additional 25% of prostate cancer patients had stable disease (above the 50% with objective clinical responses). Additionally, the researchers considered the drug well tolerated, though the fairly high percentage experiencing nausea and vomiting did not appeal to me.

    The media release quoted Susan Domchek, MD, Director of the University of Pennsylvania’s Basser Research Center for BRCA statement that as many as 3% of pancreatic and prostate cancer patients have the BRCA1 or BRCA2 inherited mutation. I’m wondering what percentage of lethal prostate cancer that would represent. I suspect it is a fairly large percentage, and if so, PARP inhibition could become a very important element of therapy.

    I checked for FDA approval and learned that this drug was not approved and that as of last August no Phase III trials were in progress, a late stage Phase III trial for ovarian cancer having been canceled. We’re going to have to wait a while to see how PARP inhibitors will pan out.

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