2016年6月1日美国食品和药品监管局(FDA)批准cobas _EGFR突变测试v2，一种为癌症药物Tarceva(厄洛替尼[erlotinib])的基于血协同诊断。这是第一个FDA-批准的，基于血基因测试可检测在非小细胞肺癌患者中上皮生长因子受体(EGFR)基因突变。在约10-20%非小细胞肺癌(NSCLC)存在这类突变。
在美国男性和女性中肺癌是癌相关死亡的主要原因和，虽然在男性中更常见，在妇女中来信肺癌的死亡数正在增加。按照美国癌症研究所，今年估计221,200美国人将被诊断有肺癌，而158,040人将死于该病。NSCLC是肺癌的最常见类型。NSCLC肿瘤可能脱落肿瘤DNA至患者的血液，使之可能在血样品中检测到特异性突变。利用血样品测试肿瘤DNA也被称为一种“液体活检。
FDA的装置和辐射卫生中心中体外诊断和辐射卫生室主任Alberto Gutierrez，Ph.D.说： “液体活检测试的批准使它可能对患者输送高度个体化卫生保健，” “液体活检还有潜能允许医生用尽可能以最小侵入性的方式确定哪个患者的肿瘤有特异性突变。”
用cobas EGFR突变测试v2，检测在患者的血样品中特异性NSCLC 突变的存在[外显子19或外显子21缺失(L858R)取代突变]帮助选择那些可能从用Tarceva治疗获益的患者。但是，如果在血中未检测到这类突变，那么应被进行一个肿瘤活检以确定是否存在NSCLC突变。只要当测试提供阳性结果，它可能对病情太差或否则不能为提供一个EGFR测试的肿瘤样品患者可能获益。
利用血样品利用该测试确定cobas EGFR突变测试v2的效力以确定纳入一项临床试验患者肿瘤活检以前确证被cobas EGFR突变测试v1确定EGFR外显子19缺失或L858R突变对中EGFR突变状态。
FDA在2004年批准Tarceva治疗有局部晚期或转移NSCLC至少一次以前化疗方案失败后患者，而在2013年，FDA批准它为有转移非小细胞有EGFR外显子19缺失或L858R取代突变当用一种FDA-批准的测试检测的肺癌患者肿瘤一线治疗。Tarceva的最常见副作用是皮疹，腹泻，缺氧，疲乏，呼吸困难，咳嗽，恶心和呕吐。建议Tarceva不与基于铂化疗组合而且未曽在转移NSCLC其肿瘤有除外显子19缺失或L858R取代突变以外中评价一线治疗。.
这个cobas EGFR突变测试v2是加州Pleasanton Roche Molecular Systems制造。Tarceva是加州Norman，Oklahoma Astellas Pharma Technologies公司制造和由加州南旧金山Genentech公司分发。
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm504488.htm
TARCEVA Rx
Pancreatic, thyroid, and other endocrine cancers
Respiratory and thoracic cancers Only 4 drugs may be compared at once
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Generic Name and Formulations:
Erlotinib (as HCl) 25mg, 100mg, 150mg; tabs.
Company:
Astellas Pharma US, Inc. and Genentech, Inc.
Select therapeutic use: Pancreatic, thyroid, and other endocrine cancers
Respiratory and thoracic cancers
Indications for TARCEVA:
In combination with gemcitabine: first-line treatment of locally advanced, unresectable or metastatic pancreatic cancer.
Adult:
Take on empty stomach. 100mg once daily + gemcitabine (see full labeling). Use until disease progression or unacceptable toxicity occurs. Diarrhea unresponsive to loperamide, severe skin reactions, strong CYP3A4 inhibitors (see Interactions), hepatic impairment: reduce in 50mg decrements. Concomitant CYP3A4 inducers (see Interactions): increase in 50mg increments at 2-week intervals; max 450mg (see full labeling). Concurrent cigarette smoking: increase in 50mg increments at 2-week intervals; max 300mg (see full labeling); upon cessation, reduce to 150mg or 100mg daily.
Children:
Not established.
Warnings/Precautions:
Discontinue if interstitial lung disease, severe hepatic toxicity, GI perforation, severe bullous, blistering or exfoliating skin conditions, or corneal perforation or severe ulceration occurs. Withhold or consider discontinuing therapy if severe renal failure due to dehydration, or acute/worsening ocular disorders occur. Monitor LFTs periodically; withhold in patients without history of hepatic impairment for total bilirubin >3XULN or transaminases >5XULN, or in patients with history of hepatic impairment or biliary obstruction for doubling of bilirubin or tripling of transaminases over baseline. Discontinue if abnormal LFTs do not improve or resolve within 3 weeks. Withhold for persistent severe diarrhea unresponsive to loperamide, severe rash, or grade 3–4 keratitis. Monitor renal function, serum electrolytes, pulmonary function, INR, prothrombin time. History of peptic ulcers or diverticular disease. Pregnancy (Cat.D); use effective contraception during therapy and at least 2 weeks after the last dose. Nursing mothers: not recommended.
Interactions:
Potentiated by CYP3A4 inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, grapefruit) and CYP1A2 inhibitors (eg, ciprofloxacin); avoid if possible. Plasma levels decreased by CYP3A4 inducers (eg, rifampin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, St. John's wort), proton pump inhibitors or H2 blockers (take erlotinib 10hrs after and at least 2hrs before next dose), and smoking; avoid if possible. Increased risk of GI perforation with concomitant anti-angiogenic agents, steroids, NSAIDs, taxane-based chemotherapy. Monitor for bleeding with oral anticoagulants, NSAIDs.
Pharmacological Class:
Kinase inhibitor.
Adverse Reactions:
Rash, diarrhea, nausea, vomiting, anorexia, fatigue, elevated LFTs, unexplained pulmonary symptoms (eg, dyspnea, cough, fever; discontinue and follow-up if occurs), stomatitis, infection; rare: GI perforation (may be fatal), ocular disorders (eg, conjunctivitis, keratitis, corneal ulceration/perforation), MI/ischemia, hemolytic anemia, cerebrovascular accidents, interstitial lung disease; hepatic or renal failure and hepatorenal syndrome (may be fatal); bullous, blistering and exfoliative skin conditions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis).
Note:
Testing considerations: K-RAS mutation analysis, EGFR amplification analysis
How Supplied:
Tabs—30
Indications for TARCEVA:
First-line treatment in patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test. Maintenance treatment of patients with locally advanced or metastatic NSCLC whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. Treatment of locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen.
Limitations Of use:
Do not use in combination with platinum-based chemotherapy. Not eva luated as first-line treatment in patients with metastatic NSCLC whose tumors have EGFR mutations other than exon 19 deletions or exon 21 (L858R) substitution.
Adult:
Take on empty stomach. 150mg once daily. Use until disease progression or unacceptable toxicity occurs. Diarrhea unresponsive to loperamide, severe skin reactions, strong CYP3A4 inhibitors (see Interactions), hepatic impairment: reduce in 50mg decrements. Concomitant CYP3A4 inducers (see Interactions): increase in 50mg increments at 2-week intervals; max 450mg (see full labeling). Concurrent cigarette smoking: increase in 50mg increments at 2-week intervals; max 300mg (see full labeling); upon cessation, reduce to 150mg or 100mg daily.
Children:
Not established.
Warnings/Precautions:
Discontinue if interstitial lung disease, severe hepatic toxicity, GI perforation, severe bullous, blistering or exfoliating skin conditions, or corneal perforation or severe ulceration occurs. Withhold or consider discontinuing therapy if severe renal failure due to dehydration, or acute/worsening ocular disorders occur. Monitor LFTs periodically; withhold in patients without history of hepatic impairment for total bilirubin >3XULN or transaminases >5XULN, or in patients with history of hepatic impairment or biliary obstruction for doubling of bilirubin or tripling of transaminases over baseline. Discontinue if abnormal LFTs do not improve or resolve within 3 weeks. Withhold for persistent severe diarrhea unresponsive to loperamide, severe rash, or grade 3–4 keratitis. Monitor renal function, serum electrolytes, pulmonary function, INR, prothrombin time. History of peptic ulcers or diverticular disease. Pregnancy (Cat.D); use effective contraception during therapy and at least 2 weeks after the last dose. Nursing mothers: not recommended.
Interactions:
Potentiated by CYP3A4 inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, grapefruit) and CYP1A2 inhibitors (eg, ciprofloxacin); avoid if possible. Plasma levels decreased by CYP3A4 inducers (eg, rifampin, rifabutin, rifapentine, phenytoin, carbamazepine, phenobarbital, St. John's wort), proton pump inhibitors or H2 blockers (take erlotinib 10hrs after and at least 2hrs before next dose), and smoking; avoid if possible. Increased risk of GI perforation with concomitant anti-angiogenic agents, steroids, NSAIDs, taxane-based chemotherapy. Monitor for bleeding with oral anticoagulants, NSAIDs.
Pharmacological Class:
Kinase inhibitor.
Adverse Reactions:
Rash, diarrhea, nausea, vomiting, anorexia, fatigue, elevated LFTs, unexplained pulmonary symptoms (eg, dyspnea, cough, fever; discontinue and follow-up if occurs), stomatitis, infection; rare: GI perforation (may be fatal), ocular disorders (eg, conjunctivitis, keratitis, corneal ulceration/perforation), MI/ischemia, hemolytic anemia, cerebrovascular accidents, interstitial lung disease; hepatic or renal failure and hepatorenal syndrome (may be fatal); bullous, blistering and exfoliative skin conditions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis).
Note:
Testing considerations: K-RAS mutation analysis, EGFR amplification analysis
How Supplied:
Tabs—30 |
