Personalized medicine is coming to life in management of advanced prostate cancer


A new study reported today in the New England Journal of Medicine is suggesting that every man with metastatic prostate cancer (regardless of his age or family history) should be tested for certain particular inherited mutations.

The mutations in question are the ones that affect a man’s capacity for DNA repair, e.g., BRCA2, ATM, CHEK2, BRCA1, RAD51D, and PALB2.

The study by Pritchard et al. states that 84 germline DNA-repair gene mutations that were presumed to be deleterious were identified in 82 of the 534 men for whom relevant data was gathered (11.8%); mutations were found in 16 genes altogether, including all of the six mentioned above.

The data provided by Pritchard et al. are also supported by a detailed blog post on the Memorial Sloan-Kettering Cancer Center web site.

Also, Genomic Health and Epic Biosciences have apparently agreed to a deal to commercialize the new test for the AR-V7 mutation that can help to tell whether a man with advanced prostate cancer is or is not likely to respond well to treatment with either abiraterone acetate (Zytiga) or enzalutamide (Xtandi). Information about this agreement can be found in a media release on the Genomic Health web site and (for subscribers) a story in the Wall Street Journal.

What is clear from these two new reports is the degree to which we are starting to see the need for detailed genetic and similar testing of men with advanced forms of prostate cancer in order to be able to optimize the quality of their treatment and their likely outcomes. Such testing may also help us to avoid the unnecessary, inappropriate, and expensive treatment of men with types of therapy that are highly unlikely to work for them as individuals.

It will undoubtedly take some time before all this becomes “standard practice” outside the major academic medical centers, but it is also clear that any patient with an advanced form of prostate cancer (M0 or M1 disease, or castration-resistant disease — whether metastatic or not) should be asking his doctors whether such testing is appropriate in his particular case.

2 Responses

  1. Olaparib (a PARP inhibitor made by AstraZeneca) was approved for treatment of certain prostate cancers early this year. I believe (and I’m going from memory here) that these PARP inhibitors are being approved by the FDA only in conjunction with certain types of companion diagnostics. BRCA gene status must be determined. Plus there are additional tests (called HRD tests) which attempt to measure the degree to which DNA repair capability has been degraded in the specific tumor tissue. This has been a very good predictor of whether the PARP inhibitor drugs will be effective or not. And, is a big leap forward in “personalized medicine”.

    Testing for genetic variants that a person is born with, and are present in every cell of the person’s body can be useful. Testing actual specific cancer cells to see whether they are likely to respond to a given treatment is a big, big step. As you said, this will save money, needless side effects, time wasted on useless treatment, etc.

    (The PARP gene is a backup DNA repair mechanism. If the BRCA genes are defective, and cannot perform their repair function, PARP genes take over. If a drug stops the PARP gene function, the DNA repair process can be so degraded that the cells will die.)

  2. This story was also reported by Laurie McGinley in this morning’s Washington Post.

    The reporter did a nice job, though carrying forward the semantic issue whether non-metastatic advanced cancer is included.

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