近日，FDA批准特罗凯（Tarceva，通用名erlotinib，厄洛替尼）用于经FDA批准的试剂盒检测证实其肿瘤中存在特定的表皮生长因子受体（EGFR）激活性突变（activating mutations）的转移性非小细胞肺癌（NSCLC）患者的初始（一线）治疗。 批准日期：2013年5月15日 公司：美国基因泰克 TARCEVA(厄洛替尼[Erlotinib]) 片剂, 用于口腔使用 美国初步批准: 2004 最近的重大变化 适应症和用法, 非小细胞肺癌 (NSCLC): 10/2016 剂量和administration:06/2016 剂量和管理, 剂量 modifications:05/2016 警告和预防措施, 脑血管 accident:10/2016 警告和预防措施, 胚胎-胎儿 toxicity:10/2016 作用机制 表皮生长因子受体 (EGFR) 表达在正常和癌细胞的细胞表面。在某些肿瘤细胞中, 通过这种受体发出信号在肿瘤细胞存活和增殖中起着重要作用, 无论 EGFR 的突变状态如何。尼布可逆抑制 EGFR 的激酶活性, 防止与受体相关的酪氨酸残留 autophosphorylation, 从而抑制进一步的下游信号。尼布结合亲和性的 EGFR 外显子19删除或外显子 21 (L858R) 突变高于其亲和性的野生类型受体。尼布抑制其他酪氨酸激酶受体没有充分的特征。 适应症和用法 特罗凯是一种激酶抑制剂, 表示为: ·治疗转移性非小细胞肺癌 (NSCLC) 患者, 其肿瘤有表皮生长因子受体 (EGFR) 外显子19项缺失或外显子21(L858R) 替代突变, 经FDA批准的检测接受一线,维持, 或第二或更高线治疗后, 至少有一个预先化疗方案的进展。 •First 治疗局部晚期、不可切除或转移性胰腺癌的患者, 并与吉西他滨结合。 使用限制: 特罗凯的•Safety和疗效尚未建立在肺癌患者的肿瘤有其他 EGFR 突变。 •TARCEVA 不建议与铂基化疗结合使用。 剂量和管理 •NSCLC: 150mg 口服, 空腹, 每日一次。 •Pancreatic 癌症: 100mg 口服, 空腹, 每日一次。 剂型和强度 片剂: 25mg, 100mg, 150mg 禁忌 没有. 警告和预防措施 •Interstitial肺部疾病 (ILD): 发生在1.1% 的患者。不特罗凯新的或渐进的无法解释的肺部症状, 如呼吸困难, 咳嗽和发烧的急性发作。如果ILD被诊断, 停止特罗凯。 •Renal失败: 监测肾功能和电解质, 特别是在有脱水风险的患者。保留特罗凯严重肾毒性。 •Hepatotoxicity: 发生于或无肝损害, 包括肝功能衰竭和肝肾综合征: 监测周期性肝检测。中止或停止特罗凯严重或恶化的肝脏测试。 •Gastrointestinal穿孔: 停止特罗凯。 •Bullous 和脱落皮肤紊乱: 停止特罗凯。 •Cerebrovascular意外 (中风): 胰腺癌患者的中风风险增加。 •Microangiopathic溶血性贫血(诗): 胰腺癌患者的发病风险增加。 •Ocular 障碍: 停止特罗凯角膜穿孔, 溃疡或持续性严重角膜炎。 •Hemorrhage 的患者服用华法林: 定期监测 INR 的患者服用华法林或其他香豆素衍生物抗凝剂。 •Embryo-胎儿毒性: 可引起胎儿伤害。向女性提供对胎儿潜在危险的生殖潜能, 并使用有效避孕措施。 不良反应 最常见的不良反应(≥ 20%) 与特罗凯的联合分析, 在所有经批准的治疗线, 无EGFR突变, 胰腺癌患者皮疹, 腹泻, 厌食, 疲劳, 呼吸困难, 咳嗽、恶心和呕吐。 药物相互作用 · CYP3A4抑制剂或联合CYP3A4和CYP1A2抑制剂增加尼布血浆浓度。避免伴随使用。如果不可能, 减少特罗凯剂量。 · CYP3A4诱导剂降低尼布血浆浓度。避免伴随使用。如果不可能, 增加特罗凯剂量。 •Cigarette吸烟和CYP1A2诱导剂减少尼布血浆浓度。避免伴随使用。如果不可能, 增加特罗凯剂量。 •Drugs增加胃pH值, 降低尼布血浆浓度。质子泵抑制剂避免伴随使用, 如果可能的话。对于H-2受体拮抗剂, 服用特罗凯后10小时H-2受体拮抗剂剂量。用于与抗酸剂, 单独剂量的几个小时。 在特定人群中使用 哺乳: 不哺乳 如何提供/存储和处理 25毫克片剂: 圆, 凸透镜面和直边, 白色涂膜, 在橙色印以 "T" 和 "25" 在一边和平原在另一边;提供的: 瓶 30: NDC 50242-062-01 100毫克片剂: 圆, 凸透镜面和直边, 白色涂膜, 在灰色与 "T" 和 "100" 在另一边和平原打印;提供的: 瓶 30: NDC 50242-063-01 150毫克片剂: 圆形, 凸透镜面和直边, 白色涂膜, 在栗色与 "T" 和 "150" 在另一边和平原打印;提供的: 瓶 30: NDC 50242-064-01 在 25°c (77°F) 贮存;允许的远足-30°c (59°F-86°F)。请参阅 USP 控制室温。 完整说明书附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=57bccb29-1c47-4c64-ab6a-77960a91cc20 Avastin and Tarceva in combination significantly improves the time patients with advanced lung cancer can live without their disease worsening Roche today announced interim results from a phase III study (ATLAS) in patients with advanced non small cell lung cancer (NSCLC). The study was stopped early because of the significance of the interim data. The results showed that Tarceva (erlotinib) plus Avastin (bevacizumab) given as first line maintenance treatment following initial therapy with Avastin plus chemotherapy extends the time patients live without their disease getting worse (progression free survival) compared to maintenance therapy with Avastin plus placebo. The results will be welcome news for patients and their physicians as extending the time patients live without their disease advancing is a key treatment aim in lung cancer. Most people with lung cancer are diagnosed with advanced stage disease and die within 12 months of diagnosis1. “ATLAS is the second study to show that people with lung cancer who took the daily pill Tarceva following initial treatment lived longer without their cancer getting worse” said William M. Burns, CEO Division Roche Pharmaceuticals. “ The results build on the strong data currently available for Avastin in first line treatment and Tarceva in second line therapy, and offer a new option to help extend the time these patients live without their disease progressing.’’ A preliminary safety analysis showed adverse events were consistent with previous Avastin or Tarceva studies, as well as trials evaluating the two medicines together, and no new safety signals were observed. Avastin and Tarceva are already available for the treatment of patients with advanced lung cancer in the US and Europe. Avastin used first line is proven to deliver the longest survival times for patients while Tarceva has a proven record as second and third line treatment for advanced lung cancer. In addition, the SATURN study showed that Tarceva when given in first line maintenance – immediately following initial treatment with platinum based chemotherapy – significantly extended the time patients with NSCLC lived without their cancer getting worse compared to placebo. Data from the ATLAS study will be submitted for presentation to a forthcoming medical meeting. Roche plans to discuss these data with the regulatory authorities to determine next steps. About ATLAS (AVF3671g) ATLAS is a global, multicentre, randomised, double blind, placebo controlled study that enrolled 1,157 patients with locally advanced, recurrent or metastatic NSCLC. Patients were initially given first line treatment of four cycles of Avastin in combination with investigators’ choice of multiple chemotherapy regimens (carboplatin/gemcitabine, carboplatin/paclitaxel, carboplatin/docetaxel, cisplatin/vinorelbine, cisplatin/docetaxel or cisplatin/gemcitabine). If their cancer did not progress and they did not experience significant toxicity, patients were then randomised (n=768) to receive maintenance therapy with Avastin plus Tarceva or Avastin plus placebo until disease progression. The study’s primary efficacy endpoint was post-chemotherapy PFS, defined as the length of time from randomisation to either disease progression or death on study treatment. Secondary endpoints included overall survival, incidence of all and serious adverse events, and incidence of treatment discontinuation. About lung cancer Lung cancer is the single biggest cancer killer in Europe, claiming 334,800 lives in 20062. Unfortunately, the majority of NSCLC cases are still diagnosed at an advanced stage when the cancer is inoperable or has already spread to another part of the body. In spite of the use of chemotherapy as the first line treatment option, less than 5% of people with advanced NSCLC survive for five years after diagnosis and most die within 12 months1. About Avastin Avastin is a novel medicine that inhibits the growth of a network of blood vessels that supply nutrients and oxygen to cancerous tissues. Avastin received its first license in 2004 in the US and 2005 in the European Union for first line treatment for patients with metastatic colorectal cancer and received approval for first line treatment for patients with advanced NSCLC in 2006 in the US and 2007 in Europe. In Europe Avastin is currently used to treat patients with four cancer types (breast cancer, lung cancer, colorectal cancer and renal cell cancer), which collectively cause nearly 3 million deaths each year. There are more than 450 ongoing clinical trials investigating the use of Avastin in over 30 tumour types with the hope that Avastin’s full potential can be realised for people with cancer all over the world. Avastin has changed the way cancer is being treated and has already helped more than 350,000 people with cancer live longer and more productive lives. About Tarceva Tarceva is the first and only epidermal growth factor receptor (EGFR) oral targeted agent in second line with a proven and significant survival and symptom benefit in a broad range of patients with advanced lung cancer without the toxic side effects of chemotherapy. Tarceva has been approved in the EU since September 2005 and in the US since November 2004 for the treatment of patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen. Furthermore Tarceva in combination with chemotherapy is the first treatment in over a decade to have shown a significant survival benefit in treating patients with pancreatic cancer. It is approved in the US in combination with gemcitabine for the first line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer and in the EU for treatment of metastatic pancreatic cancer. Since its initial launch three years ago, Tarceva has been used to treat more than 200,000 patients and has been approved in over 80 countries worldwide. About Roche Headquartered in Basel, Switzerland, Roche is one of the world’s leading research-focused healthcare groups in the fields of pharmaceuticals and diagnostics. As the world’s biggest biotech company and an innovator of products and services for the early detection, prevention, diagnosis and treatment of diseases, the Group contributes on a broad range of fronts to improving people’s health and quality of life. Roche is the world leader in in vitro diagnostics and drugs for cancer and transplantation, and is a market leader in virology. It is also active in other major therapeutic areas such as autoimmune diseases, inflammatory and metabolic disorders and diseases of the central nervous system. In 2007 sales by the Pharmaceuticals Division totalled 36.8 billion Swiss francs, and the Diagnostics Division posted sales of 9.3 billion francs. Roche has R&D agreements and strategic alliances with numerous partners, including majority ownership interests in Genentech and Chugai, and invested over 8 billion Swiss francs in R&D in 2007. Worldwide, the Group employs about 80,000 people. Additional information is available on the internet at www.roche.com All trademarks used or mentioned in this release are protected by law.