Tagrisso（osimertinib 中文药名：奥斯替尼片）于2015年11月13日获美国FDA是一款最新治疗晚期非小细胞肺癌（NSCLC）患者的口服药物授予加速批准。现被批准用于肿瘤有特定表皮生长因子受体（EGFR）突变（T790M）及其它EGFR阻断剂治疗后疾病恶化的患者。
批准日期：2015年11月13日 公司：阿斯利康
TAGRISSO™（奥斯替尼[osimertinib]）片剂，用于口服用途
美国首次批准：2015年
适应症和用法
TAGRISSO是用于治疗转移性表皮生长因子受体的治疗所示的激酶抑制剂（EGFR）的T790M突变阳性的非小细胞肺癌（NSCLC），由FDA批准的试验，谁取得了进展上或EGFR后所检测TKI治疗。
这个指示下，根据肿瘤缓解率和缓解时间加速审批核准。继续批准该适应症可能是在验证和临床获益描述验证试验队伍。
用法用量
•确认T790M突变在肿瘤标本之前与TAGRISSO开始治疗的存在。
•80毫克口服，每日一次，有或没有食物。
剂型和规格
片剂：80毫克和40毫克
禁忌
无。
警告和注意事项
•间质性肺疾病（ILD）/肺炎：多发生在患者的3.3％。永久停止TAGRISSO患者诊断为ILD /肺炎。
•QTc间隔延长：监控心电图和电解质的患者谁有历史或倾向QTc延长，或谁正在服用的已知延长QT间期的药物。扣压然后重新启动减低剂量或永久停止TAGRISSO。
•心肌病：发生率为1.4％。治疗前评估左室射血分数（LVEF），然后每3个月以后。
•胚胎 - 胎儿毒性：TAGRISSO可致胎儿危害。奉劝女性潜在的风险对胎儿，并在与TAGRISSO治疗6周最后一剂后使用有效的避孕方法。奉劝男性使用有效避孕4个月，TAGRISSO的最后一次给药后。
不良反应
最常见的不良反应（≥25％）为腹泻，皮疹，皮肤干燥，指甲毒性。
要报告疑似不良反应，请联系阿斯利康在1-800-236-9933或www.TAGRISSO.com或FDA电话1-800-FDA-1088或www.fda.gov/medwatch。
药物相互作用
•强CYP3A抑制剂：如果可能的话，避免并发管理与TAGRISSO。如果没有替代存在，患者应密切关注的毒性症状监测。
•强CYP3A诱导剂：避免，如果可能的，因为同时使用可能会降低osimertinib血药浓度。
特殊人群中使用
哺乳期：不要哺乳。
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产地国家：美国
原产地英文商品名:
TAGRISSO tablets 40mg/Tablet 30Tablets/bottle
原产地英文药品名:
osimertinib
中文参考商品译名:
TAGRISSO片 40毫克/片  30片/瓶
中文参考药品译名:
奥斯替尼
生产厂家中文参考译名:
阿斯利康制药
生产厂家英文名:
AstraZeneca

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产地国家：美国
原产地英文商品名:
TAGRISSO tablets 80mg/Tablet 30Tablets/bottle
原产地英文药品名:
osimertinib
中文参考商品译名:
TAGRISSO片 80毫克/片  30片/瓶
中文参考药品译名:
奥斯替尼
生产厂家中文参考译名:
阿斯利康制药
生产厂家英文名:
AstraZeneca

TAGRISSO™ (osimertinib) (AZD9291) Approved By The US FDA As Treatment For Patients With EGFR T790M Mutation-Positive Metastatic Non-Small Cell Lung Cancer
2015 /US Food and Drug Administration (FDA) has approved TAGRISSO™ (osimertinib) (AZD9291) 80mg once-daily tablets for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, who have progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy.
TAGRISSO is the only approved medicine indicated for patients with metastatic EGFR T790M mutation-positive non-small cell lung cancer. This indication is approved under the FDA's accelerated approval process based on tumor response rate and duration of response (DoR).
TAGRISSO is an EGFR-TKI, a targeted cancer therapy, designed to inhibit both the activating, sensitizing mutations (EGFRm), and T790M, a genetic mutation responsible to EGFR-TKI treatment resistance. Nearly two-thirds of NSCLC patients who are EGFR mutation-positive and experience disease progression after being treated with an EGFR-TKI develop the T790M resistance mutation, for which there have been limited treatment options.
Pascal Soriot, Chief Executive Officer, AstraZeneca, said: "The FDA approval of TAGRISSO marks an important milestone for lung cancer patients who urgently need new treatment options. We have built on our heritage in this area and acted on the breakthrough clinical evidence to ensure this next-generation medicine reaches patients in record time. As we advance our comprehensive lung cancer portfolio, we have the opportunity to treat greater numbers of patients across all stages of this disease through precision medicines, immunotherapies and novel combinations."
Pasi A Jänne M.D., PhD, Director, Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, Scientific Director, Belfer Center for Applied Cancer Science and Professor of Medicine, Harvard Medical School said: "In the AURA clinical studies, TAGRISSO has demonstrated compelling early efficacy and tolerability in patients with EGFRm T790M metastatic non-small cell lung cancer. This treatment has the potential to become the standard of care for patients living with EGFRm T790M non-small cell lung cancer. The accelerated approval of TAGRISSO highlights its clinical promise for a targeted group of patients and gives healthcare providers an important new option."
AstraZeneca has collaborated with Roche to develop the cobas® EGFR Mutation Test v2 as the companion diagnostic for TAGRISSO. The cobas® EGFR Mutation Test v2 is intended to identify a range of EGFR mutations in patients with non-small cell lung cancer, including T790M.
TAGRISSO was granted Fast Track, Breakthrough Therapy, Priority Review and Accelerated Approval status by the FDA. In Europe and Japan, TAGRISSO was granted Accelerated Assessment and Priority Review status respectively. Interactions with regulatory authorities in the rest of the world are ongoing.
The FDA approval of TAGRISSO is based on data from the two AURA Phase II studies (AURA extension and AURA2) which demonstrated efficacy in 411 EGFRm T790M NSCLC patients that had progressed on or after an EGFR TKI. In those trials, overall objective response rate ((ORR) a measurement of tumor shrinkage) was 59% (95% CI: 54% to 64%). In a separate part of the AURA Study in 63 patients, ORR was 51% and median duration of response was 12.4 months.
The TAGRISSO tolerability profile showed that no individual severe grade 3+ adverse events occurred at = 3.5%.The most common adverse events were generally mild to moderate and included diarrhea (42% all grades; 1.0% Grade 3/4), rash (41% all grades; 0.5% Grade 3/4), dry skin (31% all grades; 0% Grade 3/4), and nail toxicity (25% all grades; 0% Grade 3/4).
Osimertinib (AZD9291) Development Program
Osimertinib (AZD9291) is being studied in the confirmatory trial, AURA3, an open label, randomized Phase III study designed to assess the efficacy and safety of osimertinib (AZD9291) versus platinum-based doublet chemotherapy in patients with EGFR T790M positive, locally advanced, or metastatic NSCLC who have progressed following prior therapy with an EGFR-TKI. Osimertinib (AZD9291) is also being investigated in the adjuvant setting and in the metastatic first-line setting, including in patients with brain metastases, as well as in combination with other compounds.
Important Safety Information
•There are no contraindications for TAGRISSO
•Interstitial Lung Disease (ILD)/Pneumonitis occurred in 3.3% and were fatal in 0.5% of 813 TAGRISSO patients. Withhold TAGRISSO and promptly investigate for ILD in any patient presenting with worsening of respiratory symptoms indicative of ILD (e.g., dyspnea, cough and fever). Permanently discontinue TAGRISSO if ILD is confirmed
•QTc interval prolongation occurred in TAGRISSO patients. Of the 411 patients in two Phase II studies, one patient (0.2%) was found to have a QTc greater than 500 msec, and 11 patients (2.7%) had an increase from baseline QTc greater than 60 msec. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life threatening arrhythmia
•Cardiomyopathy occurred in 1.4% and were fatal in 0.2% of 813 TAGRISSO patients. Left Ventricular Ejection Fraction (LVEF) decline >10% and a drop to <50% occurred in 2.4% of (9/375) TAGRISSO patients. Assess LVEF before initiation and then at 3 month intervals of treatment. Withhold TAGRISSO if ejection fraction decreases by 10% from pretreatment values and is less than 50%. For symptomatic congestive heart failure or persistent asymptomatic LV dysfunction that does not resolve within 4 weeks, permanently discontinue TAGRISSO.
•Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during TAGRISSO treatment and for 6 weeks after the final dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the final dose.
•The most common adverse reactions (>20%) observed in TAGRISSO patients were diarrhea (42%), rash (41%), dry skin (31%) and nail toxicity (25%).
About Non-Small Cell Lung Cancer
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-third of all cancer deaths, more than breast, prostate and colorectal cancers combined. Lung cancer has a five-year survival rate that is less than 20%. Approximately 85% of all lung cancers in the US are NSCLC; 10% to 15% of these are EGFR mutation-positive. Approximately two-thirds of patients treated with EGFR TKI therapy will acquire resistance related to the T790M mutation.
About TAGRISSO
TAGRISSO™ (osimertinib) (AZD9291) 80mg once-daily tablet is the first medicine indicated for the treatment of metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive NSCLC, as detected by an FDA-approved test, who have progressed on or after EGFR TKI therapy.