>>Do you have any comments regarding the seemingly increased gap of time between interim and predicted final analysis? It came up on the call but Sherwin wouldn't bite directly but did keep repeating about the slower onset of effect of immunotherapies.<<
One possibility is the fact that Vital-1 is a very atypical clinical trial. For example,while the interim and final results are blinded, there is no blinding at randomization since the GVAX immunotherapy treatement, described as similar to allergy shots, is different than infusing Taxotere with far more linited side effects, but both have an initial course of six months. Patients in the GVAX experimental arm can elect to continue monthly GVAX therapy after the initial six month dosing, so long as they do not commence another therapy, but there is no restriction otherwise from starting any therapy, including Taxotere. The GVAX single arm Ph2 trials not only showed that the same high dosing subgroup (n=32) as is being used in Vital 1 had a median survival of some 35 months, but as of 9/07, the even smaller subgroup (n=9) that had subsequent Taxotere, had still not reached median survival at 40 months. The positive impact that subsequent Taxotere has on cancer vaccine efficacy was also seen with Provenge as well as with Therion's PROSTVAC. So imagine, the experimental arm patients start the initial GVAX 6 month therapy and so long as they don't progress, they take monthly boosters. Chances are the immediate impact on PSA etc. is initially much more pronounced in the Taxotere arm, but even if subsequent GVAX were beneficial, there is no crossover to GVAX and no really good follow-on options exist for that group. OTOH, if a GVAX patient progresses to symptomatic AIPC, their oncologist would undoubtedly recommend Taxotere, since it not only is the indicated standard of care for symptomatic patients, but is better for pain relief than mitoxantrone. In addition, they would be aware of the putative major survival benefit arising from Taxotere after GVAX. Ultimately, therefore, the number of early events in the GVAX and Taxotere arms and their event rate might not differ much, but given more time, the experimental arm would in effect become a combination GVAX + Taxotere arm. The event rate in the Taxotere arm would remain the same, but the event rate in the combination arm would decline substantially, which could have the effect of increasing the elapsed calendar time between the interin and the final looks as compared to any elapsed period from the start of enrollment to the interim.
That also ties in to a reason for the Vital 2 trial. Vital 1 would only demonstrate value in asymptomatic AIPC, so patients deferring any therapy until they become symptomatic technically would not be offered GVAX. Testing simultaneous GVAX and Taxotere as compared to Taxotere alone in symptomatic AIPC addresses that need. All JMHO.
