2阿帕替尼临床数据解读-1221.pptVIP

临床特别关注的不良反应，n(%) AE名称 试验组 安慰剂组 N=176 N=91 全部 III-IV 全部 III-IV 骨髓抑制 白细胞减少 64 (36.4) 3 (1.7) 8 (8.8) 0 中性粒细胞减少 60 (34.1) 10 (5.7) 9 (9.9) 1 (1.1) 血小板减少 41 (23.3) 5 (2.8) 6 (6.6) 1 (1.1) 贫血 32 (18.1) 9 (5.1） 22 (24.4) 3 (3.3) 心脏毒性 心电图异常 5 (2.8) 1 (1.1) 1 (1.1) 0 急性心梗 1 (0.6) 1 (0.6) 0 0 出血 黑便 21 (11.9) 2 (1.14) 13 (14.2) 3 (3.3) 呕血 1 (0.6) 1 (0.6) 0 0 咯血 1 (0.6) 1 (0.6) 0 0 肠梗阻 1 (0.6) 1 (0.6) 0 0 蛋白尿 78 (44.3) 4 (2.3) 15 (16.5) 0 肝脏毒性 转氨酶升高 35 (19.9) 11 (6.3) 10 (11.0) 2 (2.2) 总胆红素升高 29 (16.5) 4 (2.3) 9 (9.9) 5 (5.5) 高血压 62 (35.2) 8 (4.5) 8 (4.6) 0 手足综合症 49 (27.8) 15 (8.5) 1 (1.1) 0 安全性小结 阿帕替尼组药物暴露时间明显长于安慰剂组。 与Ⅱ期临床试验的安全性观察结果基本吻合。 多数不良事件发生可预期、可耐受、可控制、可逆转。 结 论 阿帕替尼可显著延长二线治疗失败晚期胃癌患者生存期和无进展生存期 阿帕替尼试验组不良反应类型及发生率与已上市的同类小分子VEGFR抑制剂常见不良事件一致，且多数不良事件可控 阿帕替尼的批准将为二线治疗失败晚期胃癌患者提供新的治疗选择 Apa研究对胃癌的治疗有重大意义 全球第一个晚期胃癌标准化疗失败后被证实安全有效的抗血管生成靶向药 胃癌靶向药物中唯一一个口服制剂，极大提高患者依从性 为胃癌化疗失败患者提供新的标准治疗方案 Vascular endothelial growth factor (VEGF) that is secreted by tumour and stromal cells, including macrophages, endothelial cells and fibroblasts, has multiple functions in the tumour microenvironment, which involve the ability of VEGF to interact with VEGF receptors that are expressed on different cell types. VEGF functions as a primary stimulus for angiogenesis, which is a process that involves the ability of VEGF receptors to stimulate signalling pathways that induce the proliferation and the migration of endothelial cells, and the ability of these cells to degrade and to remodel the extracellular matrix. These processes culminate in sprouting angiogenesis and the formation of new blood vessels. VEGF can also increase vascular permeability, which results in the deposition of a provisional fibrin matrix that triggers the formation of desmoplastic stroma. By contrast, VEGF secreted by tumour cells functions in an autocrine manner and promotes dedifferentiation and an epithelial– mesenchymal transition phenotype, with a consequent enhancement of tumour invasion and survival, and it ca