Sunday morning’s news from the ASCO annual meeting


We commented earlier on several of the prostate cancer presentations given this morning at the American Society for Clinical Oncology (ASCO) meeting — see here and here. However, there was another important paper presented this morning.

De Wit et al. (see abstract no. 5008) formally reported the results of a second, large, Phase III clinical trial of orteronel (TAK-700) + prednisone in the treatment of chemotherapy-naive, metastatic, castration-resistant prostate cancer (mCRPC). Unfortunately the results of this trial (as with the previous trial in post-chemotherapy mCRPC patients) are not good enough to support an approval of orteronel + prednisone for the treatment of advanced prostate cancer. This is clearly a second major setback for the potential of orteronel as a potential treatment for prostate cancer, and it is hard to see that the developers will pursue the potential of this product for much longer.

The results of this trial clearly showed that treatment with orteronel + prednisone was able to delay the onset of radiographic progression in this group of patients. However, this delay in radiographic progression was not confirmed by a true overall survival benefit, and orteronel + prednisone was also associated with a number of significant side effects compared to placebo + prednisone.

The base results of the trial were as follows:

  • 1,560 men with chemotherapy-naive mCRPC were enrolled in the trial.
  • Median radiographic progression-free survival times at an interim analysis were
    • 11.0 months for patients randomized to orteronel + prednisone
    • 8.3 months for patients randomized to a placebo + prednisone
    • This result was statistically significant (hazard ratio [HR] = 0.7, P < 0.001)
  • Median radiographic progression-free survival times at the final study analysis were
    • 13.8 months for patients randomized to orteronel + prednisone
    • 8.7 months for patients randomized to a placebo + prednisone
    • This result was also statistically significant (HR = 0.7, P < 0.00001)
  • Median overall survival times at the final study analysis was
    • 31.4 months for patients randomized to orteronel + prednisone
    • 29.5 months for patients randomized to a placebo + prednisone
    • This result was not statistically significant (HR = 0.9, P = 0.314)
  • Several other secondary endpoints showed a potential value for orteronel + placebo, but …
  • 30 percent of patients on orteronel + prednisone discontinued therapy because of adverse events (as compared to 18 percent of patients randomized to a placebo + prednisone.
  • Common side effects included nausea, fatigue, constipation, and diarrhea.

There are numerous possible reasons why orteronel was unable to demonstrate a real clinical value in the two Phase III trials now completed, including the fact that many of the patients enrolled in this second study may have been too sick at time of enrollment to gain any benefit from orteronel therapy.

It is becoming more challenging to show a real survival benefit among men with mCRPC — unless one is able to identify specific subsets of these patients who can be targeted based on genomic or other relevant markers. However, this doesn’t men that further progress is going to be impossible. It simply means that newer drugs are probably going to have to work on different drivers of the development of mCRPC, and there are already a number of drugs that may be capable of this (e.g., galeterone, as shown in the poster session [abstract no. 5029] on Saturday).

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