Pharma Strategy Blog

Recently, ASCO held its annual symposium on GI cancers, which covers a variety of tumour types including pancreatic, colorectal, gastrointestinal, renal and prostate cancers. In this blog review, we will concentrate on an update on prostate cancer.

There is a clear unmet need in hormone-resistant prostate cancer (HRPC) because conventional anti-androgen therapy can stop working after a few years of treatment, leaving a population of men whose cancer no longer responds to treatment and who have a limited life expectancy. Taxotere, a chemotherapeutic agent, is the only FDA-approved drug to treat HRPC and was approved in 1996 on the basis of a 2.5 month survival advantage.  The therapy also has significant adverse events associated with it, including myelosuppression and risk of febrile neutropenia. 

Much of the noise surrounding new treatments for HRPC have centred around Cougar Biotech's abiraterone and Dendreon's Provenge.  

The former announced an update in chemo-naive HRPC. Data on the 31 evaluable patients treated in the trial were reported in a poster by Ryan et al.  77% patients experienced a decline in prostate specific antigen (PSA) levels of greater than 30%, 71% experienced a PSA decline of greater than 50% and 26% experienced PSA declines of greater than 90%.  Median time to PSA progression had not yet been reached, with patients continuing to be treated for 10+ months.  Of the 33 evaluable patients with tumour lesions that were measurable by the RECIST criteria, treatment with abiraterone resulted in partial radiological responses in 24% patients, stable disease in 39% patients and progressive disease in 12% patients; 24% patients were still awaiting radiographic disease assessment.

Cougar has a special protocol assessment for two planned registrational trials of abiraterone – one in a post-chemotherapy population and the other in the pre-chemo/post-androgen deprivation therapy population.   Data from the smaller trial, in the post-chemo population, could be available late this year or early in 2010.  The primary endpoint is overall survival.  

The main reason for all the excitement, I suspect, is because the therapy is a pill and early results from previous announcements suggest that it may be much better tolerated than Taxotere, which will be much better for the elderly population for whom it will be targeted towards.

One therapeutic mentioned at the meeting that I found interesting and novel was Mediavation's MDV3100, an androgen receptor antagonist.  Researchers at Memorial Sloan Kettering in New York presented the initial phase I/II data on PK and anti-tumour activity.  They concluded that MDV3100 was: 

"Generally tolerated with encouraging anti-tumor activity as assessed by PSA declines, CTC changes, imaging findings, and time on treatment. The data suggest a dose-response trend with consistency across endpoints." 

"The pivotal Phase 3 IMPACT study of PROVENGE® (sipuleucel-T) in men with advanced prostate cancer met its primary endpoint of improving overall survival compared to a placebo control. The magnitude of the survival difference observed in the intent to treat population resulted in the study successfully achieving the pre-specified level of statistical significance defined by the study's design. The safety profile of PROVENGE appeared to be consistent with prior trials."