乳腺癌生物靶向治疗进展资料.ppt

Royce slides Japan Oct 2002 * How about clinical data, Do we have data based on evidence-based medicine to prove that lapatanib is an promising drug? In this year ASCO meeting, with Refractory, progressive metastatic or locally advanced HER2+ breast cancer. All patients have received anthracycline, Taxane, or trastuzumab. there was an prospective, randomized phase III trial reported. This trial compared Lapatinib + Capecitabine with Capecitabine only in the management of patients The target population was 528 patients as planed, however, when 321 patients were enrolled, the trial was closed by Independent Data Monitoring Committee, or IDMC for short, due to superiority of combination arm in primary endpoint. The primary endpoint of this trial was time to progression, or TTP for short. Royce slides Japan Oct 2002 * ITT, intent to treat. This trial showed that Combination arm had a longer time to progression, 36.9 vs 19.7 wks (P = .00016); For progression-free survival, it was 36.9 vs 17.9 wks (P = .000045); Due to a short follow-up, there was no overall survival advantage for combination arm. For objective response rates, there was a trend to a higher response rate with the combination arm, as you can see, the combination arm was 22.5%, but single agent arm was only 14.3%. Summary of Key Conclusions No clinical benefit in patients with metastatic breast cancer (MBC) treated with gefitinib and trastuzumab. Time to progression is shorted. Nearly two thirds experienced at least grade 1/2 rash and/or diarrhea. * 3. 单抗药物存在问题 据Genentech报告，使用贝伐单抗治疗10月将花费4.4万美元 由于血液稀释，肿瘤血管屏障，抗体穿透性能差等因素而造成肿瘤内的抗体剂量低 肿瘤细胞的异质性，目前的抗体治疗是针对肿瘤细胞的某个特异性受体，单一清除含有某种受体的肿瘤细胞并不代表能治愈肿瘤。 鼠源单克隆抗体，易引起排斥反应 * 单克隆抗体 100% 35% 5-10% 0% * 单抗药物英文名称中词缀的含义及其中文译名 英文词缀 中文词缀 来源 来源 -omab —莫单抗 mouse 鼠源 -ximab —昔单抗 chimera 嵌合体 -zumab —组单抗 humanized 人源化 -imab —伊单抗 primate 灵长目源 -umab —人单抗 human 完全人化 * 单抗药物存在问题 Human anti-mouse antibodies (HAMA) 晚期卵巢癌免疫闪烁扫描术(immunoscintigrap