抗血管生成药物研发历程和临床应用.pptVIP

在小鼠模型中，植入肿瘤细胞及抗VEGF治疗后血管再生情况 对照组 抗VEGF治疗* 抗血管生成药物副反应发生机制 抗血管生成药物副反应可能发生机制总结 不同抗血管生成药物的副反应不同 贝伐珠单抗严重不良事件发生率低 贝伐珠单抗中国人群主要不良事件数据 常见不良事件的监测 常见不良事件的分级与处理 常见不良事件的分级与处理 少见不良事件的处理 少见不良事件的处理（续） 抗血管生成药物安全性小结 抗血管生成治疗药物副反应不同于传统化疗药物副反应 大部分副反应是因为VEGF的正常功能抑制引起的 抗血管生成治疗药物单抗与TKI的副反应不同 同一副反应不同药物的发生率不同 贝伐珠单抗严重不良事件少见 贝伐珠单抗副反应可以管理 Reference Miller KD, Wang M, Gralow J et al. Paclitaxel plus Bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 2007;357:2666–76. This slide shows median PFS for Bevacizumab plus paclitaxel in trial E2100. A significant increase in median PFS, as determined by the trial investigators, was observed in patients receiving Bevacizumab plus paclitaxel compared with paclitaxel alone (11.4 vs 5.8 months, respectively). The HR for progression was 0.42. The increase in median PFS reported by the investigators was confirmed by an IRF, with 11.3 months in the combination arm and 5.8 months in the paclitaxel arm (HR=0.48). The IRF confirmation is robust, as ECOG succeeded in collecting scans from around 90% of patients. Both of these analyses were conducted in accordance with the prespecified and FDA-approved methods in the Statistical Analysis Plan and IRF charter, including: intent to treat analysis of all randomised patients, with the February 9, 2005 data cut-off date applied, and using the same PFS definition and censoring rules. These data are not only highly statistically significant, but also clinically meaningful for MBC patients. ECOG = Eastern Cooperative Oncology Group; FDA = USA Food and Drug Administration; HR = hazard ratio; IRF = Independent Review Facility; MBC = metastatic breast cancer; PFS = progression-free survival Reference Klencke B et al. Independent review of E2100 validates progression-free survival (PFS) improvement with the addition of Bevacizumab (B) to paclitaxel (P) as initial chemotherapy for metastatic breast cancer (MBC). J Clin Oncol 2008;26:50s (Abstract 1036). Reference Miles D, Chan A, Romieu