GSK Tykerb/赫赛汀组合疗法III期乳腺癌ALTTO研究失败

GSK Tykerb/赫赛汀组合疗法III期乳腺癌ALTTO研究失败

                               
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发布日期：2014-06-04  来源：新药汇
【新药汇www.xinyaohui.com讯】 葛兰素史克Tykerb/Herceptin III期HER2阳性乳腺癌辅助治疗ALTTO研究未能达到改善无病生存期的主要终点，这2种药物均为抗HER2药物。

                               
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葛兰素史克（GSK）6月2日公布了乳腺癌III期ALTTO研究的数据。该项研究在HER2阳性早期乳腺癌患者中开展，调查了2种HER2药物lapatinib（拉帕替尼，商品名Tykerb/Tyverb）+trastuzumab（曲妥珠单抗，商品名：赫赛汀，Herceptin）组合疗法作为一种辅助疗法，用于HER2阳性乳腺癌的治疗。数据表明，与trastuzumab单药辅助疗法相比，lapatinib+trastuzumab组合辅助疗法未能达到改善无病生存期（DFS）的主要终点。该项研究中安全性与既往一致，无心的安全信号。相关数据已提交至美国临床肿瘤学会（ASCO）第50届年会。
拉帕替尼（lapatinib）为一种新的EGFR靶向治疗药物，是一种口服的小分子表皮生长因子（EGFR:ErbB-1，ErbB-2）酪氨酸激酶抑制剂，与已批准上市的人源化单克隆抗体药物赫赛汀（Herceptin，通用名：曲妥珠单抗，trastuzumab）作用机制不同，Tykerb对曾经使用曲妥珠单抗治疗，而且效果不明显的部分HER2阳性乳癌患者有效。lapatinib主要用于联合卡培他滨治疗HER2受体过度表达且既往接受过包括蒽环类、紫杉醇、曲妥珠单抗(赫赛汀)治疗的晚期或转移性乳腺癌。
lapatinib目前已获批用于乳腺癌及一些实体瘤的治疗，该药在欧洲以商品名Tyverb销售，在美国以商品名Tykerb销售。
肿瘤的有效治疗手段一直以手术切除为主，除外科手术之外的治疗均称为辅助治疗。新辅助治疗（neoadjuvant therapy）是指在手术治疗前予以的治疗措施，主要包括化疗和放疗，其目的是减小肿瘤的体积，使其能够更容易手术移除。
英文原文：GSK announces Phase III ALTTO results for anti-HER2 therapy combination in the adjuvant breast cancer treatment setting
GlaxoSmithKline plc (LSE: GSK) today announced that the Phase III study of two anti-HER2 agents, lapatinib (Tykerb™/Tyverb™) and trastuzumab, did not meet the primary endpoint of improved disease free survival (DFS) compared to single agent therapy with trastuzumab as adjuvant treatment for HER2 positive early breast cancer. The safety profile was consistent with the established safety profile of the study drugs, with no new safety signals observed.
These results were presented today at the 50th Annual Meeting of the American Society of Clinical oncology (ASCO) in Chicago, Illinois.
The primary analysis of the study tested for superiority (p≤0.025) between the combination arm and trastuzumab alone with respect to DFS; the trastuzumab followed by lapatinib arm was tested for non-inferiority (p≤0.025). The results showed that at four years, 88 percent of women lived without their disease returning (4-year DFS) in the lapatinib plus trastuzumab arm and 86 percent in the trastuzumab arm [HR 0.84 (97.5% CI, 0.70-1.02; p=0.048)]. The 4-year DFS rate for the trastuzumab followed by lapatinib arm was 87 percent compared to 86 percent in the trastuzumab arm [HR 0.96 (97.5% CI, 0.80-1.15; p=0.061)].
Adverse events (AEs) more frequently reported in the lapatinib plus trastuzumab arm compared to the trastuzumab arm were diarrhoea (75% vs. 20%), rash (55% vs. 20%) and hepatobiliary (23% vs. 16%). Diarrhoea, grade 3 or higher, was increased in all lapatinib containing treatment arms (5-15%), compared to trastuzumab alone (1%). The incidence of febrile neutropenia was <1% across treatment arms and primary cardiac endpoints were <1% in all arms. Overall, fatal AEs were consistent between treatment groups (<1%), with no clear pattern to the reported events. AEs leading to discontinuation were higher in the lapatinib containing arms (23% in the combination arm) compared with the trastuzumab arm (8%).
about ALTTO
ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation trial; NCT00490139) is a randomised, multi-centre, open-label, Phase III study of adjuvant lapatinib, trastuzumab, their sequence and their combination in patients with HER2 positive primary breast cancer. Randomised patients received anti-HER2 therapy (lapatinib, trastuzumab) after completing all chemotherapy, concurrent with a taxane following anthracycline, or concurrent with a non-anthracycline, platinum-containing regimen.
ALTTO randomised 8,381 patients at nearly 1,000 research sites in 44 countries. Patient enrolment began in June 2007 and was completed in July 2011.  The lapatinib arm was discontinued in 2011, after an independent review committee determined that the lapatinib alone arm was unlikely to meet the pre-specified criteria to demonstrate non-inferiority to trastuzumab alone with respect to disease-free survival.
about lapatinib
Lapatinib— an orally active, reversible, small molecule TKI that potently inhibits both ErbB1 and ErbB2 tyrosine kinase activity—is marketed as Tykerb™ in the U.S. and as Tyverb™ in Europe and other countries across the world. Lapatinib is not approved or licensed anywher in the world for the treatment of HER2 positive early breast cancer.
Tykerb™ and Tyverb™ are trademarks of the GSK group of companies.

呜呜，只能看中文的，英语好差啊