课件：肾癌靶向治疗研究进展.pptVIP

* * Nexavar Phase II Study in Adjuvant RCC: ASSURE Study * * 54 * * * * cyclin * * * I don’t remember the use of ECOG performance status. Only Karnofsky was used, so we should omit ECOG and keep it strictly Karnofsky. Also, ECOG PS 1 would correspond only to Karnofsky 80-100. ECOG 2 would be Karnofsky 60-70 * * Agree this is better. Also, I think the log–rank p values should be included here, since they represents survival comparisons over the entire study period, not just median survival. I would like Steve’s opinion on this. * In preparation for cliical testing, the murine Ab used in the animal studies was humanized to minimize immunogenicity. As you can see from this cartoon, the entire Ab has been humanized with the exception of a small fraction in the variable region. The antibody binds all isoforms of VEGF A with high affinity and has terminal half life of 2-3 wks * Randomized, double-blind, Ph II comparing placebo and 2 doses of BV (3 mg/kg and 10 mg/kg) given every 2 weeks N=150 (50/arm permitted to allow for some pts who could not be evaluated) Power: 80% power and overall alpha 0.05 to detect a doubling of the hazard ratio for each of the 2 primary comparisons (3 vs placebo, 10 vs placebo) [doubling of TTP I pts receiving either dose of BV vs placebo] Primary Endpoints: TTP RR Secondary Endpoint: OS (Crossover from placebo to 3 mg/kg + thalidomide was allowed.) toxicity Lab correlate: Plasma VEGF and serum levels of BV were measured (3.5.F.8 murine Ab) Stratified for prior IL-2 therapy Loading dose of BV (150% of assigned dose) administered as 2-hour infusion, then assigned dose given one week later q 2 wks thereafter Response via bi-dimensional tumor measures and standard criteria at that time; more stringent, Initial 5 week evaluation: pts w/ 2 cm increase in any lesion, significant PS deterioration, or new. Severe symptoms were removed from study; in all subsequent evals, pts off study for PD * Bevacizumab significantly p