FDA 過了Kadcyla (trastuzumab emtansine) !! 開發藥物難以承受之重~

FDA approves Roche's Kadcyla (trastuzumab emtansine), the first antibody-drug conjugate for treating HER2-positive metastatic breast cancer MONDAY, 25 FEBRUARY 2013  Roche (SIX: RO, ROG; OTCQX: RHHBY) announced that the U.S. Food and Drug Administration (FDA) has approved Kadcyla (trastuzumab emtansine or T-DM1) for the treatment of people with HER2-positive metastatic breast cancer (mBC) who have received prior treatment with Herceptin (trastuzumab) and a taxane chemotherapy. Kadcyla is the fourth medicine from Roche to receive FDA approval for people with advanced cancers within the past two years. An antibody-drug conjugate (ADC) is a new kind of targeted cancer medicine that can attach to certain types of cancer cells and deliver chemotherapy directly to them. Kadcyla is the first FDA-approved ADC for treating HER2-positive mBC, an aggressive form of the disease. "Kadcyla is an antibody-drug conjugate representing a completely new way to treat HER2-positive metastatic breast cancer, and it helped people in the EMILIA study live nearly six months longer," said Hal Barron, M.D., Roche's Chief Medical Officer and Head, Global Product Development. "We currently have more than 25 antibody-drug conjugates in our pipeline and hope this promising approach will help us deliver more medicines to fight other cancers in the future." Kadcyla is made up of the antibody, trastuzumab, and the chemotherapy, DM1, joined together using a stable linker. Kadcyla combines the mechanisms of action of both trastuzumab and DM1, and it is the first Roche ADC approved by the FDA. Roche has studied ADC science for more than a decade and has eight ADCs in Phase I or Phase II studies for different types of cancer. Roche has also submitted a Marketing Authorisation Application to other Regulatory Authorities around the world, including the European Medicines Agency (EMA), for Kadcyla for the treatment of people with HER2-positive mBC. This application is currently under review by the EMA.

Kadcyla efficacy in HER2-positive mBC The FDA approval of Kadcyla is based on results from EMILIA (TDM4370g/BO21977), an international, Phase III, randomised, open-label study comparing Kadcyla alone to lapatinib in combination with Xeloda (capecitabine) in 991 people with HER2-positive locally advanced breast cancer or mBC who had previously been treated with Herceptin and a taxane chemotherapy. Results include:(1) The study met both co-primary efficacy endpoints of overall survival and progression-free survival (PFS; as assessed by an independent review committee). People who received Kadcyla lived a median of 5.8 months longer (overall survival) than those who received the combination of lapatinib and Xeloda, the standard of care in this setting (median overall survival: 30.9 months vs. 25.1 months). People receiving Kadcyla experienced a 32 percent reduction in the risk of dying compared to people who received lapatinib and Xeloda (HR=0.68; p=0.0006). People who received Kadcyla lived significantly longer without their disease getting worse (PFS) compared to those who received lapatinib plus Xeloda (HR=0.65, 35 percent reduction in the risk of disease worsening or death, p<0.0001; median PFS 9.6 months vs. 6.4 months). No new safety signals were observed and adverse events (AEs) were consistent with those seen in previous studies, with fewer people who received Kadcyla experiencing Grade 3 or higher (severe) AEs than those who received lapatinib plus Xeloda (43.1 percent vs. 59.2 percent). For people receiving Kadcyla, the most common (occurring in more than 2 percent of participants) Grade 3 or higher AEs were low platelet count (14.5 percent), increased levels of enzymes released by the liver and other organs (8.0 percent), low red blood cell count (4.1 percent), low levels of potassium in the blood (2.7percent), nerve problems (2.2percent) and tiredness (2.5percent).

About Kadcyla Kadcyla is an ADC being studied in HER2-positive cancers. It is the first ADC to result from Roche and Genentech's 30 years of HER2 pathway research and the third medicine Roche has developed for the treatment of HER2-positive breast cancer. Like Herceptin, Kadcyla binds to HER2-positive cells and is thought to block out-of-control signals that make the cancer grow while also calling on the body's immune system to attack the cancer cells. Once Kadcyla is taken up by those cells, it is designed to destroy them by releasing the DM1 inside the cells. Roche licenses technology for Kadcyla under an agreement with ImmunoGen, Inc.

【FDA】晚期乳腺癌新药T-DM1获批 发布时间：2013-2-25 来源：药品资讯网信息中心 美国食品和药物管理局（FDA）2月22日批准Kadcyla(ado-trastuzumab emtansine)用于治疗HER-2阳性晚期转移性乳腺癌。 HER2是一种在细胞表面正常生长的相关蛋白。它在某些类型的癌细胞（HER2阳性）数量增加，其中包括一些乳腺肿瘤。在这些HER2阳性乳腺癌中，HER2蛋白数量增加有助于癌细胞的生长和存活。Kadcyla目标是用于治疗已经接受过曲妥珠单抗和一线紫杉烷类化疗无效的乳腺癌患者。"Kadcyla是将曲妥珠单抗与一种干扰肿瘤细胞的生长的药物DM1相结合" FDA的药品评价和研究中心的血液学和肿瘤学产品办公室主任Richard Pazdur博士介绍说，"Kadcyla将药物输送至肿瘤灶使肿瘤缩小，延缓疾病进展，延长生存期。这是第四个批准的针对于HER2蛋白的药物。"在临床研究过程中Kadcyla被简称为T-DM1，其接受了FDA的优先审查程序。当没有有效的替代治疗存在或与已批准药物相比能够提供显著的生存改善时，FDA将提供快速的六个月的药物审查程序，由此为患者提供安全有效的治疗。其他FDA批准的用于治疗HER2阳性乳腺癌的药物分别为：曲妥珠单抗（1998年），拉帕替尼（2007年）和帕妥珠单抗（2012年）。Kadcyla的安全性和有效性通过一项临床研究确认，共991例患者，随机分配到接受Kadcyla或拉帕替尼联合卡培他滨。患者接受治疗直至癌症进展或不良反应无法耐受。这项研究的目的是患者的无进展生存（患者没有发生肿瘤进展的时间长度）和总生存期（患者在死亡之前的生存时间长度。 结果表明：接受Kadcyla治疗的患者中位无进展生存期为9.6个月，拉帕替尼联合卡培他滨治疗的患者为6.4个月。在Kadcyla组的患者中位总生存期为30.9个月，而拉帕替尼联合卡培他滨组为25.1个月。具体内容：NEJM：研究证明T-DM1治疗乳腺癌具备安全性和有效性Kadcyla批准时有一项黑框警告，提醒患者与卫生保健专业人员：该药物可引起肝脏毒性，心脏毒性和死亡。该药物同时也可以导致危及生命的严重出生缺陷，在使用Kadcyla进行治疗之前要进行妊娠试验。使用Kadcyla治疗患者最常见的不良反应有恶心、乏力、肌肉或关节疼痛、血小板水平降低（血小板减少）、肝酶水平升高、头痛和便秘。 乳腺癌是妇女第二大癌症相关死亡原因。根据美国国家癌症研究所提供的数据，估计2013年美国将有232340名妇女被诊断患有乳腺癌，39620名患者将死于乳腺癌。近20%乳腺癌患者的HER2蛋白数量有扩增。 Kadcyla、曲妥珠单抗和帕妥珠单抗均由加利福尼亚州南圣弗朗西斯科的基因泰克上市销售，该公司是罗氏集团的下属公司。拉帕替尼由葛兰素史克上市销售。