【ASCO 2012】T-DM1显著改善HER2阳性乳腺癌结局
2012-06-04 00:00:00来源：医脉通阅读：28次
根据ASCO 2012年会全体会议上的一项研究结果，与卡倍他滨和拉帕替尼的标准治疗相比，曲妥珠单抗emtansine（T-DM1）（罗氏/基因泰克）可以显著提高HER2阳性局部晚期或转移性乳腺癌的无进展生存期，这些妇女之前接受过紫杉类和曲妥珠单抗治疗。T-DM1和标准治疗的中位无进展生存期分别为9.6和6.4个月，差异有统计学意义。
Sunil Verma博士讲到，研究表明T-DM1相比卡倍他滨和拉帕替尼可以显著提高无进展生存期，在总生存上也有有利的趋势。在一个采访中，Verma博士指出，使用曲妥珠单抗和拉帕替尼治疗HER2阳性乳腺癌已经取得了巨大的进步。T-DM1的理念就是精准化疗，直接传递化疗药物到靶细胞。这是治疗转移性HER2阳性乳腺癌患者的治疗新选择，应该成为标准治疗的一部分。
T-DMI是一种免疫抗体结合物：其中曲妥珠单抗充当制导装置，将具有细胞毒性的DM1传递到HER2阳性的癌细胞上。目前这些药物的组合还在研究中。例如，MARIANNE临床试验正在研究帕妥珠单抗和T-DM1一线治疗HER2阳性乳腺癌。
研究细节
EMILIA临床试验是一项随机3期的国际研究，将T-DM1与卡倍他滨和拉帕替尼（标准治疗）的疗效进行对比。研究纳入了991名HER2阳性转移性乳腺癌病人，之前使用过曲妥珠单抗和紫杉类治疗。
共有978名病人接受了治疗。T-DM1组和标准治疗组的中位随访期分别为12.9个月和12.4个月。T-DM1和标准治疗的中位无进展生存期分别为9.6和6.4个月，差异有统计学意义。临床结局详见下表。
题目：Primary results from EMILIA, a phase III study of trastuzumab emtansine (T-DM1) versus capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC) previously treated with trastuzumab (T) and a taxane.（Abstract LBA1）
作者：Kimberly L. Blackwell, David Miles, et al.
英文摘要
Background: T-DM1 is an antibody-drug conjugate comprising T, a stable linker, and the potent cytotoxic agent DM1; it incorporates the antitumor activities of T and the HER2-targeted delivery of DM1. Methods: EMILIA is a randomized study of T-DM1 vs XL, the only approved combination for T-refractory HER2+ MBC. Patients (pts) received T-DM1 (3.6 mg/kg IV q3w) or X (1000 mg/m2 PO bid, days 1–14 q3w) + L (1,250 mg PO daily) until progressive disease (PD) or unmanageable toxicity. Pts had confirmed HER2+ MBC (IHC3+ and/or FISH+), and prior therapy with T and a taxane. Primary end points were PFS by independent review, OS and safety. An interim OS analysis (efficacy boundary: HR= 0.617; p=0.0003) was planned at the time of the final PFS analysis. Results: 991 pts were enrolled; 978 received treatment. Median (med) durations of follow-up were 12.9 (T-DM1) and 12.4 (XL) months (mo). Baseline demographics, prior therapy and disease characteristics were balanced. There was a significant improvement in PFS favoring T-DM1 (med 9.6 vs 6.4 mo; HR=0.650 [95% CI, 0.549–0.771]; p <0.0001). The med T-DM1 OS was not reached vs 23.3 mo (HR=0.621 [95% CI, 0.475–0.813]; p=0.0005); the interim efficacy boundary was not crossed. T-DM1 was well tolerated with no unexpected safety signals. The most common grade ≥3 adverse events (AEs) per treatment were for T-DM1: thrombocytopenia (12.9% vs 0.2%), increased AST (4.3% vs 0.8%), and increased ALT (2.9% vs 1.4%); for XL: diarrhea (20.7% vs 1.6%), palmar plantar erythrodysesthesia (16.4% vs 0) and vomiting (4.5% vs 0.8%). The table lists other end points. Conclusions: T-DM1 conferred a significant and clinically meaningful improvement in PFS compared with XL. Other end points support T-DM1 as an active and well-tolerated novel therapy for HER2+ advanced BC.
作者：Kimberly L. Blackwell, David Miles, et al.
英文摘要
Background: T-DM1 is an antibody-drug conjugate comprising T, a stable linker, and the potent cytotoxic agent DM1; it incorporates the antitumor activities of T and the HER2-targeted delivery of DM1. Methods: EMILIA is a randomized study of T-DM1 vs XL, the only approved combination for T-refractory HER2+ MBC. Patients (pts) received T-DM1 (3.6 mg/kg IV q3w) or X (1000 mg/m2 PO bid, days 1–14 q3w) + L (1,250 mg PO daily) until progressive disease (PD) or unmanageable toxicity. Pts had confirmed HER2+ MBC (IHC3+ and/or FISH+), and prior therapy with T and a taxane. Primary end points were PFS by independent review, OS and safety. An interim OS analysis (efficacy boundary: HR= 0.617; p=0.0003) was planned at the time of the final PFS analysis. Results: 991 pts were enrolled; 978 received treatment. Median (med) durations of follow-up were 12.9 (T-DM1) and 12.4 (XL) months (mo). Baseline demographics, prior therapy and disease characteristics were balanced. There was a significant improvement in PFS favoring T-DM1 (med 9.6 vs 6.4 mo; HR=0.650 [95% CI, 0.549–0.771]; p <0.0001). The med T-DM1 OS was not reached vs 23.3 mo (HR=0.621 [95% CI, 0.475–0.813]; p=0.0005); the interim efficacy boundary was not crossed. T-DM1 was well tolerated with no unexpected safety signals. The most common grade ≥3 adverse events (AEs) per treatment were for T-DM1: thrombocytopenia (12.9% vs 0.2%), increased AST (4.3% vs 0.8%), and increased ALT (2.9% vs 1.4%); for XL: diarrhea (20.7% vs 1.6%), palmar plantar erythrodysesthesia (16.4% vs 0) and vomiting (4.5% vs 0.8%). The table lists other end points. Conclusions: T-DM1 conferred a significant and clinically meaningful improvement in PFS compared with XL. Other end points support T-DM1 as an active and well-tolerated novel therapy for HER2+ advanced BC.