曲妥珠单抗联合拉帕替尼及多西紫杉醇一线治疗HER-2阳性晚期乳腺癌的安全性和有效性  

The toxicity and efficacy of trastuzumab combined with lapatinib and docetaxel as first line treatment for HER-2 positive advanced breast cancer

作　　者：段海波[1] 胡倩 林颖欣[1] 曹硕[1] 蓝晓珊[1] 庞丹梅[1] Duan Haibo;Hu Qian;Lin Yingxin;Cao Shuo;Lan Xiaoshan;Pang Danmei(The First People's Hospital of Foshan,Guangdong Foshan 528000,China)

机构地区：[1]佛山市第一人民医院,广东佛山528000

出　　处：《现代肿瘤医学》2020年第18期3159-3163,共5页Journal of Modern Oncology

基　　金：佛山市卫生和计划生育局医学科研课题(编号:20190045)。

摘　　要：目的:观察曲妥珠单抗联合拉帕替尼及多西紫杉醇一线治疗HER-2阳性晚期乳腺癌的安全性和有效性。方法:这是一项前瞻、单臂、开放标签的单中心Ⅱ期临床研究(ChiCTR1800015814)。HER-2阳性晚期乳腺癌一线治疗给予曲妥珠单抗(6 mg/kg,首剂8 mg/kg)联合拉帕替尼(1000 mg/d)及多西紫杉醇(75 mg/m^2),每3周重复。对非进展的患者继续用药直至疾病进展或毒性不可耐受,但最长用药时间不超过2年。主要研究终点是有效率,次要终点是PFS和OS。结果:自2016年9月至2019年5月共入组65例患者。本方案的剂量限制性毒性为腹泻,Ⅲ-Ⅳ度腹泻发生率为24.6%。总体有效率为69.2%(CR 3.1%,PR 66.1%),激素受体阴性患者有效率明显优于激素受体阳性患者(76.7%vs 57.1%,P<0.01)。中位随访31个月,PFS为16.4个月(95%CI:13.4~19.6个月)。尚未达到中位OS时间。Log-rank检验显示是否内脏转移、是否多器官转移对PFS的影响具有统计学意义(P<0.01和P=0.022)。结论:曲妥珠单抗联合拉帕替尼及多西紫杉醇毒性可耐受,疗效较好,作为HER-2阳性晚期乳腺癌一线治疗新的治疗策略,值得进一步研究。Objective:To investigate the toxicity and efficacy of trastuzumab combined with lapatinib and docetaxel as first-line therapy for HER-2 positive advanced breast cancer.Methods:This was a prospective,single arm,open-label,single center phaseⅡclinical trial(ChiCTR1800015814).Trastuzumab(8 mg/kg first dose,6 mg/kg thereafter,per 3 weeks)plus lapatinib(1000 mg,daily)and docetaxel(75 mg/m^2,per 3 weeks)were administered to HER-2 positive advanced breast cancer patients as first-line treatment.For nonprogression patients,the treatment continued until disease progression or intolerable toxicity within 2 years.The primary end point was objective response rate(ORR),and the secondary end point was PFS and OS.Results:65 cases were recruited from September 2016 to May 2019.The dose-limiting toxicity of this regimen was diarrhea,with 24.6%gradeⅢ/Ⅳtoxicity.The overall ORR was 69.2%(CR 3.1%and PR 66.1%,respectively),and the ORR in hormone receptor negative group was significantly superior than in hormone receptor positive group(76.7%vs 57.1%,P<0.01).With median follow up 31 months,the PFS was 16.4 months(95%CI:13.4~19.6 months).The median OS was not reached.Visceral involvement and the number of metastatic organs had significant influence on PFS according to Log-rank analysis(P<0.01 and P=0.022,respectiveley).Conclusion:The trastuzumab combined with lapatinib and docetaxel was safe and effective,which need further investigation as a new strategy for HER-2 positive advanced breast cancer first line treatment.

关 键 词：晚期乳腺癌 HER-2阳性 曲妥珠单抗 拉帕替尼 

分 类 号：R737.9[医药卫生—肿瘤]