The other topic, which was obviously sensitive for CEGE yesterday, and may be for DNDN, is the permissive use of subsequent Taxotere after GVAX in Vital 1 and after Provenge in 9902b. DNDN finessed this subject in the Briefing Materials for the AC by reporting that a slightly higher percentage of the control group in 9901 had received subsequent Taxotere, suggesting that the overall increase in median survival, therefore, did not disproportionately favor the Provenge experimental arm.
The BLA indicated that DNDN performed Cox analysis adjusting for Taxotere usage and the data remained significant in favor of Provenge. In fact, for D9902a, after adjustment for Taxotere, the pvalue improved from .32 to .12 (page 72). Below is an excerpt related to the integrated data:
"Sensitivity analyses similar to those performed for Studies 1 and 2 were performed on the integrated Study 1 and 2 survival results. The treatment effect was consistent among study sub-populations defined by 21 known or potential baseline prognostic factors. The final model that was developed for Study 1 was applied to the integrated data. After adjusting for the 5 factors in the final model, the treatment effect remained strong (HR = 1.86 [95% CI: 1.31, 2.63]; P < 0.001). The treatment effect also remained after adjustment for docetaxel use following investigational therapy (HR = 1.50 [95% CI: 1.07, 2.08]; P = 0.017). Prostate cancer-specific survival revealed an HR of 1.72 ([95% CI: 1.21, 2.44]; P = 0.002)."
