ASCO commentary and update no. 1


On Saturday there were two major prostate cancer sessions and additional poster sessions that included prostate cancer-related material at the annual meeting of the American Society for Clinical Oncology.

The poster session in the morning dealt with a wide variety of very early stage  investigational therapeutics. Almost none of these was specific to prostate cancer and very few of the studies looking at the possibility of drug activity in late stage solid tumors included enough prostate cancer patients to get any idea of their potential as treatments for this disease. An exception was a poster by Lubaroff et al. (abstract no. 3065) reporting data from a Phase I/II trial of an adenovirus/PSA vaccine. This study did clearly show activity of the immunotherapeutic vaccine in men with hormone-refractory prostate cancer, with induction of T-cell responses and some imoact on serum PSA levels.

An educational session, entitled “Local prostate cancer therapy: what the medical oncologist needs to know,” reviewed familiar information about all of the controversies around the diagnosis and early stage treatment of prostate cancer without offering any really new information for the well-informed patient. It was a thorough session which missed only one item that your correspondent brought up later in discussion withone of the faculty, which is the potential to use dutasteride and/or finasteride as first-line therapies in men with low-risk and perhaps intermediate-risk prostate cancerin combination with active surveillance.

The main session of the day dealt with a variety of major reports on the development of new drugs for advanced stage disease and related matters. In this commentary and update we will address the three paperspresented in that session that addressed new drug development.

Despite a glowing press release issued by OncoGenex, the data presented by Chi et al. (abstract no. 5012) was less than completely compelling in providing evidence for the clinical effectiveness of docetaxel + prednisone + OGX-011 compared to docetaxel + prednisone in first-line chemotherapy of men with metastatic, castrate-resistant prostate cancer (CRPC). The basic problem was that, although there was an evident overall survival benefit that favored the OGX-011 combination, this outcome was a secondary endpoint. The original primary endpoint for this trial was a decrease in PSA of ≥ 50 percent from the patient’s baseline PSA. Unfortunately there was no difference between the two arms of the trial with respect to achievement of this endpoint, and nor was there any difference in achievement of the secondary end-point of progression-free survival.

However, you don’t have to take my word for it. The slides Dr. Chi presented this afternoon are already available on the OncoGenex web site, along with the glowing media release. Now it should be said that OncoGenex has already committed to two phase III clinical trials of OGX-011. If the trials have a survival endpoint, and OGX-011 meets that endpoint with a survival benefit similar to that shown in the data presented by Dr. Chi (23.8 months for the OGX-011 combination compared to 16.9 months for docetaxel + prednisone) then the drug will clearly deserve to be approved. What is odd is that it should show this level of survival benefit without indicating any other supporting evidence for such a benefit.

Data presented by Kantoff et al. (abstract no. 5013) from a Phase II clinical trial of the immunotherapeutic vaccine PROSTVAC-VF were similarly confusing. In this case the vaccine therapy showed an 8.2 month overall survival benefit compared to control patients — but again, there was no other evidence to support this effectiveness, and overall survival wasn’t the primary endpoint. Since, in this trial, after failing vaccine therapy, patients went on to be treated with docetaxel-based therapies, it was suggested by the discussant that survival might be being influenced more by the docetaxel therapy than by the vaccine. Again, as with OGX-011, the question is going to be whether these data can be replicated in a Phase III randomized clinical trial in a manner that offers compelling evidence for effectiveness.

On the good side, data presented by Scher et al. (abstract no. 5011) on the effectiveness of MDV3100 in patients with progressive CRPC appeared to be somewhat more compelling. There was consistency across all endpoints in this Phase I/II trial, even though the trial included chemotherapy-naive and docetaxel-treated patients. As we have already stated elsewhere, MDV3100 will be entering Phase III clinical trials shortly, at a dose of 240 mg/d.

Thus we can expect MDV3100 to be in Phase III trials soo, we can expect OGX-011 to enter Phase III trials, and it is an open question whether PROSTVAC-VF will go into Phase III rials at all.

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