XX医科大学第一附属医院肿瘤内科《乳腺癌的内科治疗进展》精品讲稿.ppt

The RIBBON-1 trial was not designed or powered to detect a difference in overall survival. At the time of this analysis, survival results were immature, with events in only 33% of patients. However, there was a trend towards improved overall survival with Xeloda-Avastin versus Xeloda-placebo (median 29.0 versus 21.2 months, HR=0.85, p=0.27).1 At disease progression patients in the placebo arm were permitted to cross over to the Avastin arm, 69% of Xeloda-placebo patients went on to receive second-line Avastin and this may have confounded the overall survival results. 1. Robert N, et al. J Clin Oncol 2009;27(Suppl. 15s):(Abst 1005). * 一线 Avastin 联合 Xeloda 显著增加ORR* *Includes ONLY patients with measurable disease at baseline ORR* (%) 35.4? 23.6 Robert N, et al. J Clin Oncol 2009;27(Suppl. 15s):(Abst 1005) ?p=0.0097 Measurable disease, n (%) 161 (78.2) 325 (79.5) 完全缓解 部分缓解 0.6% 2.2% 一线 Avastin 联合化疗: 生存时间 Xeloda T/anthra Placebo (n=206) Avastin (n=409) Placebo (n=207) Avastin (n=415) 死亡, % 35 30 35 34 总生存, 月 中位 21.2 29.0 23.8 25.2 HR (95% CI) 0.85 (0.63–1.14) 1.03 (0.77–1.38) p value (log rank) 0.27 0.83 1年生存率, % 74 81 83 81 p value (log rank) 0.076 0.44 二线接受Avastin治疗比例, % 69 52 55 50 Robert N, et al. J Clin Oncol 2009;27(Suppl. 15s):(Abst 1005) 索拉非尼 是一种口服的抗增殖和抑制血管生成的多激酶抑制剂，作用VEGFR-1,2,3, PDGFR-b, RAF, KIT, FLT-3 已经被批准用于肾癌和肝癌的治疗 有数据表明，索拉非尼联合治疗乳腺癌的化疗药物(如卡培他滨)是安全的 1. Schneider BP. et al. JCO. 2005, 23:1782-1790; 2. Awada A, et al. Eur J Cancer. 2008; 4(suppl 12):33; 多激酶抑制剂：酪氨酸激酶受体－－VEGFR-2、 VEGFR-3、 PDGFR-b、 FLT-3和 c-KIT 丝氨酸/苏氨酸激酶－－C-Raf (Raf-1)和B-Raf1 Wilhelm S et al. Clin Cancer Res. 2004; 64:7099-7109. 同时抑制肿瘤细胞增殖和肿瘤血管生成 索拉非尼---Raf/MEK/ERK信号通路的多靶点多激酶抑制剂 索拉非尼联合卡培他滨治疗晚期乳腺癌的II期随机双盲安慰剂对照临床研究 索拉非尼400 mg bid ＋ 卡培他滨1000mg bid 14天/21天（N=115） 纳入标准 局部进展或转移性乳腺癌 HER-2阴性 2次既往化疗 排除脑转移病人 主要终点 PFS 次要终点 OS TTP ORR SOLTI-0701 安慰剂 ＋ 卡培他滨1000mg bid 14天/21天（N=114） N=220 Abstract 3LBA, Presedential session III, ESMO 2009 病人