Side effect profile of MDV3100 appears highly promising in mCRPC

According to a number of media reports today, Medivation’s investigational drug MDV3100 appears to have a relatively good safety profile, although five patients who received MDV3100 in the completed Phase III trial did have seizures.

A detailed Reuters report is available on line, as is a media release from Medivation.

According to these sources:

  • MDV3100 extended the median overall survival of men with metastatic, castration-resistant prostate cancer (mCRPC) by 4.8 months compared to a placebo (as previously announced) in men who had already been treated with at least one cycle of docetaxel-based chemotherapy.
  • Men treated with MDV3100 lived for a median of 18.4 months, compared with a median survival of 13.6 months for men taking placebo (p < 0.0001; hazard ratio [HR] = 0.631).
  • MDV3100 was superior to placebo in meeting a variety of secondary endpoints.
    • Radiographic evidence of progression-free survival (8.3 versus 2.9 months; p < 0.0001; HR = 0.404)
    • Soft tissue response rate (28.9 versus 3.8 percent; p < 0.0001)
    • Time to PSA progression (8.3 versus 3.0 months; p < 0.0001; HR = 0.249).
  • 54 percent of MDV3100 patients experienced a decline in their PSA level of  50 percent or more (as compared to just 1.5 percent of patients treated with the placebo).
  • 24.8 percent of MDV3100 patients experienced a decline in their PSA level of 90 percent or more (as compared to just 0.9 percent of patinets treated with the placebo).
  • Common side effects associated with the use of MDV3100 (in men who were also being treated with an LHRH agonist) included fatigue, diarrhea and hot flushes.
  • Significant (serious) side effects, adverse events causing patients to stop treatment, and adverse events causing death were noted in 28.4 percent of men receiving MDV3100 as compared to 33.6 percent of men treated with the placebo.
  • As mentioned above, 5 patients treated with MDV3100 experienced seizures (which should be compared to 1.5 percent of 198 patients in an earlier trial of MDV3100).
  • Other serious side effects (grade 3 or higher) evident in patients treated with MDV3100 in this Phase III trial appear to include fatigue, cardiac disorders, liver function test abnormalities, and myocardial infarction; however, in each case such side effects occurred with higher frequencies in men treated with the placebo).

MDV3100 (like abiraterone acetate and other similar agents) is still being tested in patients with chenotherapy-naive patients with mCRPC and in earlier stages of progressive prostate cancer. However, it already seem clear that MDV3100 is  at least as effective and may well be safer than abiraterone acetate. According to Reuters, Dr. Nick Vogelzang, an oncologist at the Comprehensive Cancer Centers of Nevada and chair of ASCO’s communications committee, has described these trial results as “unprecedented,” and further stated that “this is going to definitely change the way we take care of patients every day in the office.” Dr Vogelzang was not involved in this study.

It is most unusual to see results from a trial like this in which serious side effects among patients receiving the active agent are fewer than those reported among the patients treated with a placebo. On the other hand, it is clear that MDV3100 does have side effects that will need to be monitored with care if this drug is to be used widely in the “real world” (outide of carefully controlled clinical trials).

Having said that, the relatively low level of side effects compared to placebo therapy and the fact that abiraterone acetate must be given in combination with steroids such as prednisone or prednisolone does suggest that MDV3100 is currently looking like an excellent candidate for use by patients who are castration-resistant — and potentially for use earlier in the treatment of men with aggressive forms of prostate cancer.

6 Responses

  1. All our happiness is relative to our environment. This week is a happy, happy week.

  2. I certainly hope MDV3100 will prove to be all it appears to be. But can someone explain to me why comparison is made to a “placebo” and exactly what placebo is used in this and similar studies?

  3. Great stuff. Nick has been telling us about these drugs at our Us TOO meetings. I’m biased but I think it’s cool to have a leading researcher as your friend and oncologist.

  4. Herb:

    (1) Comparison was made to a placebo in studies like this because at the time the study was designed and initiatred there was no other proven (i.e., approved) therapy (for metastatic, post-docetaxel, castration-resistant prostate cancer) to which it could be compared. If you tried to design a trial for a similar new drug today, it is almost certain that you would have to compare it’s effects to abiraterone acetate.

    (2) Placebos are basically tasteless sugar tablets with a form and coating similar to the trial drug.

  5. I pray that Our Lord Jesus Christ bless all involved in finding a cure for bone cancer as I have bone cancer and cannot wait to take this new drug. Please FDA approve this drug.

    God Bless


  6. I have prostate cancer with a Gleason score of 8. I started taking MDV3100 in June and my PSA dropped from 6.93 to 1.3 ng/ml. I go back for my second follow-up in a few weeks and hope to see my PSA at zero.

    I’m in a clinical trial at the University of Washington Medical Center. So far the side effects have been infrequent diarrhea and slight fatigue. If my PSA continues to drop and the tumor shrinks as hoped, I will have surgery in early December after having been on MDV3100 for 6 months. Hopefully the biopsy of the prostate gland at that point will show no cancer cells.

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