ASCO annual meeting update no. 4


A session this morning reported on an additional group of drugs in potential development for the treatment of hormone refractory prostate cancer. (Actually it is notable that the term “castration-resistant prostate cancer” appears to be the politically correct term for this stage of disease in the oncology community today. The older term “androgen-independent prostate cancer”  seems to be outmoded.)

Beer et al. reported on a Phase I trial of the monoclonal antibody ipilimumab alone and in combination with radiotherapy in treatment of 33 patients with metastatic castration-resistant prostate cancer. While the drug alone and the drug in combination with radiotherapy appeared to have some impact on PSA, and a very small number of the patinets appeared to show some degree of actual disease remission, The “New” Prostate Cancer InfoLink got the strong impression that the cost in terms of adverse events was extremely high, including one patient death and many grade 3 and grade 4 side effects. We would not currently recommend that patients participate in this trial given what appear to be other clinical trial options with apparently superior responses to date and a lower risk for adverse events.

De Bono et al. provided a detailed report on Phase I and Phase II trials of abiraterone acetate, an innovative CYP17 inhibitor of androgen synthesis, in chemotherapy-naive and docetaxel pre-treated castration-resistant prostate cancer patients.

These trials appeared to suggest a significant potential impact of abiraterone in combination with steriod therapy (prednisone or dexamethasone), with > 50 percent declines in PSA in more than 70 percent of patients, clear responses of metastases to therapy, and a relatively modest adverse reaction profile. It would appear from the data presented that patients either do or definitively don’t respond to abiraterone. This may reflect the continuing degree of hormone-responsiveness of the individual patients, with some patient having minimal response to hormone therapy, and others maintaining a significant level of hormone response.

De Bono stated that a randomized, double blind, multicenter Phase III clinical trial of abiraterone + prednisone vs placebo + prednisone is now in development, and it will be interesting to see if this trial can show definitive impact on progression-free and overall survival.

Sher et al. provided an overview of Phase I/II trial data on the investigational agent MDV3100 in patients with progressive castration-resistant prostate cancer. MDV3100 is a novel molecule that inhibits androgen receptor function. This drug again shows highly significant reductions in PSA levels in some patients, and at the time of this presentation, the maximal therapeutic dose had still not been established. Patient recruitment to this trial is still ongoing, but it should be noted that there was a relatrively high drop-out rate from this trial, and we may again be seeing a situation in which one set of patinets may respond well to this agent and another group is not able to tolerate treatment. Further data will be necessary before the potential benefits of MDV3100 can be clearly established.

Finally, Pili et al. reported on a novel tumor vascular disrupting agent (known as DMXAA or ASA404) in combination with docetaxel for treatment of castration-resistant prostate cancer. This Phase II trial compared 33 patients receiving DMXAA + docetaxel to 38 patients receiving docetaxel alone. There are suggestions from this trial of superior outcomes on the combination arm, but The “New” Prostate Cancer InfoLink did not feel that the data were sufficiently mature at this point in time be able to establish a clear benefit for the combination therapy over docetaxel.

We would conclude by noting that the real take-away from ASCO is the increasing number of new agents that are being tested for their potential in late stage prostate cancer, and our increasing appreciation of the potential of new therapies in this stage of disease. It seems likely that, at some point relatively soon, at least one (and perhaps more than one) of these new agents or new combinations will show a truly significant impact on late stage disease — prior to, in combination with, or following chemotherapy with the current standard therapy of docetaxel and prednisone.

One Response

  1. […] The paper comes from a group headquartered in London’s Royal Marsden Hospital. It describes a Phase I study of Abiraterone Acetate, which blocks an enzyme known as Cytochrome P17, needed for the production of tesostrone. The main purpose of Phase I trials is to test toxicity, not to establish effectiveness. Readers should be aware that data from Phase II studies have already been reported — but not formally published — and that Phase III (see one our reports from ASCO earlier this year). […]

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