Olaparib continues to show promise in very late stage prostate cancer

According to a presentation at the ongoing annual meeting of the American Association for Cancer Research (AACR) meeting here in  Philadelphia, AstraZeneca’s PARP inhibiting agent — olaparib or Lynparza — continues to show promise in very late stage metastatic, castration-resistant prostate cancer.

Here’s a link to a Reuter’s report on a presentation given at the AACR meeting. Apparently 16/49 men (33 percent) with treatment-resistant, advanced prostate cancer responded to olaparib; 14 of these men had detectable DNA repair mutations. These data are results from the first part of the so-called TOPARP study being conducted at the Royal Marsden Hospital in the UK. There is  more detail in a media release issued by AACR.

Olaparib is already approved for the treatment of women with ovarian cancer and hereditary BRCA gene mutations.

4 Responses

  1. Very encouraging study of Olaparib (Lynparza) for specific population of late stage prostate cancer patients with BRCA 1/2 mutations!!!

    Thanks Sitemaster for reporting this! As a former participant survivor representative in the AACR’s wonderful, awesome Scientist Survivor Program (SSP), I would have loved to have been at this presentation. Perhaps some others of us were and can comment further. (By the way, all SSP expenses are paid including food, lodging, travel, etc., and the AACR treats us like royalty! I highly recommend the SSP program!)

    Here’s a key section from the AACR news release: “Next-generation sequencing detected mutations in genes associated with DNA repair in tumor samples from 15 of the 49 patients evaluated. Of these patients, 13 had a response to olaparib.” [Wow!]

    “The researchers calculated the specificity of the DNA repair gene panel to be 94 percent. According to Mateo, this means that 94 percent of patients without these mutations will be correctly identified as not having the mutations and this will help clinicians select the right treatment for a patient because they can be reasonably certain that olaparib will not benefit a patient testing negative for the mutations.” A report at this web site identifies the mutations as BRCA1/2 mutations, which I believe are fairly common in prostate cancer, though mostly thought of in connection with breast cancer (and ovarian cancer).

    This report also states regarding the 50 patients enrolled with metastatic, castration-resistant prostate cancer in TOPARP-A, “All had received prior docetaxel, 48 (96%) prior abiraterone, and 29 (58%) prior cabazitaxel.” Documented progression, not defined in the report, and a circulating tumor cell count (CTC) of 5 or more were inclusion requirements, suggesting that these prior treatments were deemed to no longer be successful, but I’m not positive about that. These facts mean that this drug may have a most welcome impact for a population that really needs help.

    According to that same report, one of the researchers stated that ““These are potentially the first clinical data supporting molecular stratification of treatment in prostate cancer, and we are testing this idea in the second stage of the TOPARP trial, TOPARP-B,” continued Mateo. “For TOPARP-B, we are enrolling only patients who screen positive for the DNA repair mutations linked to response in TOPARP-A.” I’m not so sure about his first sentence, as some physicians (e.g., Dr. Charles Myers) have already been using molecular stratification in clinical practice, but perhaps this is the first presented clinical trial outcome. Whatever the case, this is a most impressive use of genetic screening to select patients for a particular drug regimen. It also illustrates how researchers can now sharpen their follow-on trials to target a group of patients likely to benefit while excluding those who likely will not benefit.

    This drug is already FDA approved for some ovarian cancers in late December of 2014, making it available now, off-label, for prostate cancer. Based on the exclusion criteria, the drug appears to be a tablet, which makes it convenient.

    Wikipedia has an interesting article, especially about the up and down trial history, but that article now needs updating due to the results reported in Sitemaster’s article. AstraZeneca almost flushed this down the drain, but the results in the genetic subgroup revived it with what seems here to be stunning success. I’m pondering how many other investigative drugs that could have happened to in the past; perhaps others will now be resurrected based on genetic analysis of subgroup results.

    Chalk up another apparent success for modern, personalized medicine!

  2. Dear Jim:

    Actually BRCA1/2 mutations in patients with prostate cancer are rather rare, just as they are in women with breast and ovarian cancers — at around 2 to 3% of cases.

    Also, it is not entirely clear to me that the patients responding in this trial were all BRCA1/2 patients anyway. The only place that is mentioned is in the Practice Update report that you refer to. It is not mentioned by any other report on this study. If all the responders were BRCA1/2, I would have expected this to be stated in the AACR media release.

  3. This is the article from ScienceDaily.com that mentions defective DNA repair genes.

  4. Yes … Because it is taken directly from the AACR media release that I referred to in the commentary above.

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