A new first in the approval of drugs for the treatment of cancer


Yesterday, the US Food & Drug Administration (FDA) did something it has never done before. It approved a drug for the treatment of a type of cancer based exclusively on the presence of a specific biomarker — with no reference to the location of the cancer in the patient’s body.

The drug in question was the PD-1 inhibitor pembrolizumab (Keytruda), which has been  approved for the treatment of any metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumor. These are rare forms of cancer.

It is clear that the FDA knew exactly what it was doing. Dr. Richard Pazdur, the acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation, is quoted as saying that this approval is “an important first for the cancer community.”

The approval of pembrolizumab for this indication encompasses data from 149 patients enrolled in five distinct, relatively small clinical trials who had cancers that exhibited either MSI-H or dMMR. Apparently,

  • 15 different cancer types (based on location of the cancer) could be identified among the 149 patients treated.
  • A complete or partial response was observed in 39.6 percent of the patients.
  • The clinical responses lasted for ≥ 6 months in 78 percent of the patients who responded.

Now we need to be extremely clear that, to date, your sitemaster is not aware of the identification of any patient with prostate cancer who has ever, also been identified as having a metastatic MSI-H or dMMR form of this disease, but then again, maybe we haven’t been looking that hard for what would almost certainly be a very rare form of late stage prostate cancer.

The more important aspect of this approval, in any case, is the step that the FDA has taken to be willing to approve a drug for the treatment of cancer independent of exactly where that cancer may be located in the body — based solely on a biomarker for patient identification. This may have major implications for the future approval of other drugs for the treatment of cancer.

Having said that, we should also emphasize that this approval of pembrolizumab for this very specific indication is a provisional approval and is subject to confirmation based on data from additional data from further trials required by the FDA.

8 Responses

  1. This is a great new. Do you think FDA might do the same with PSMA?

  2. Dear Josep:

    That will depend entirely on the data that the developer of PMSA-based agents may be able to provide.

  3. We lost a man with prostate cancer last year (June 2016) briefly treated with pembrolizumab. Initially this man was evaluated for a UCSF trial run by colorectal (Emily Bergsland) — while he had MLH1 making him eligible, he also had to be qualified by MSI-H count. While qualified, he was too sick for the trial. They chose to access pembro off-label — sadly he died the day after his first infusion.

  4. I understand from Dr. Oliver Sartor (in New Orleans) that a very small number of men with prostate cancer has indeed been identified as having the mutations that might make them eligible for treatment with pembrolizumab (Keytruda) based on this indication. He also says that men with ductal cancer of the prostate appear to have a very high risk of mismatch repair defects.

    The efficacy and safety of Keytruda in such men, however, is not yet known, and while it is therefore an option we need to consider use of this treatment with caution and (ideally) relatively early in the appropriate patients.

  5. My husband Dave, who has advanced prostate cancer and is progressing on enzalutimide, was just (6/8/17) identified as having MSI-H. His MO Dr. Zibelman at Fox Chase Cancer Center (Philadelphia), who had ordered the gene testing from a new lymph node site biopsy (Caris), has him starting on pembrolizumab next week. Dave is 61 and still working 3 days a week. We are cautiously optimistic, but recognize what a big deal this might be. … The doc was happy, which was nice to see.

  6. Hi Carolyn. Thanks for this piece of information. Good luck!

  7. Carolyn:

    Do you happen to recall what gene mutation your husband exhibits?

    How are you doing with the insurance coverage for pembrolizumab?

    Good luck with the treatment. …

  8. MSH6 I think was the most relevant one but there were a whole bunch of mutations. Evidently the company was so impressed at the number they called the doctor and said, “You know that patient you sent us? …” I wish I remembered which were important because there weren’t any others on the dMMR list (I think).

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