{"id":79,"date":"2023-09-18T14:57:31","date_gmt":"2023-09-18T06:57:31","guid":{"rendered":"http:\/\/www.yaozhiyou.com\/?p=79"},"modified":"2023-09-18T14:57:32","modified_gmt":"2023-09-18T06:57:32","slug":"%e5%a5%a5%e8%a5%bf%e6%9b%bf%e5%b0%bc-azd9291-%e5%ad%9f%e5%8a%a0%e6%8b%89%e7%99%bd%e4%b9%9dincepta-osicent","status":"publish","type":"post","link":"https:\/\/www.yaozhiyou.com\/?p=79","title":{"rendered":"\u5965\u897f\u66ff\u5c3c\/azd9291\/\u5b5f\u52a0\u62c9\u767d\u4e5dincepta -Osicent"},"content":{"rendered":"\n
\"\"<\/figure>\n\n\n\n

2020-04-03 \u5206\u7c7b\uff1a\u8bf4\u660e\u4e66<\/a> \u9605\u8bfb(1141) \u8bc4\u8bba(0)<\/p>\n\n\n\n

\u6279\u51c6\u65e5\u671f: 2015\u5e7411\u670813\u65e5;\u516c\u53f8: AstraZeneca Pharmaceuticals<\/p>\n\n\n\n

\u7f8e\u56fdFDA\u6279\u51c6\u65b0\u836f\u4e38\u6cbb\u7597\u6709\u5c0f\u7ec6\u80de\u80ba\u764c\u60a3\u8005\u548c\u65b0\u8bca\u65ad\u6d4b\u8bd5\u9274\u5b9a\u88ab\u65b0\u836f\u9776\u5411\u7684\u7279\u5f02\u6027\u57fa\u56e0\u7a81\u53d8<\/p>\n\n\n\n

FDA\u7684\u836f\u54c1\u8bc4\u4ef7\u548c\u7814\u7a76\u4e2d\u5fc3\u4e2d\u8840\u6db2\u5b66\u548c\u80bf\u7624\u5b66\u4ea7\u54c1\u5ba4\u4e3b\u4efb\u8bf4\uff1a\u201c\u80ba\u764c\u7684\u5206\u5b50\u5b66\u57fa\u7840\u6211\u4eec\u7684\u4e86\u89e3\u548c\u539f\u56e0\u4e8e\u8fd9\u4e9b\u764c\u75c7\u6210\u4e3a\u5bf9\u4ee5\u524d\u6cbb\u7597\u8010\u836f\u6027\u8fc5\u901f\u5730\u88ab\u6d89\u53ca\uff0c\u201d <\/em>\u201c\u8fd9\u4e2a\u6279\u51c6\u5bf9EGFR\u8010\u836f\u6027\u7a81\u53d8\uff0cT790M\u6d4b\u8bd5\u9633\u6027\u7684\u60a3\u8005\u63d0\u4f9b\u4e00\u79cd\u65b0\u6cbb\u7597\uff0c\u548c\u662f\u6839\u636e\u6765\u81ea\u4e34\u5e8a\u8bd5\u9a8c\u5b9e\u8d28\u4e0a\u8bc1\u636e\u663e\u793a\u88abTagrisso\u6cbb\u7597\u7684\u60a3\u8005\u4e2d\u534a\u6570\u5bf9\u51cf\u5c0f\u80bf\u7624\u5927\u5c0f\u6709\u663e\u8457\u5f71\u54cd\u3002\u201d FDA\u7684\u88c5\u7f6e\u548c\u8f90\u5c04\u536b\u751f\u4e2d\u5fc3\u4e2d\u4f53\u5916\u8bca\u65ad\u548c\u8f90\u5c04\u536b\u751f\u5ba4\u4e3b\u4efb\u8bf4\uff1a\u201c\u5b89\u5168\u548c\u6709\u6548\u534f\u540c\u8bca\u65ad\u6d4b\u8bd5\u548c\u836f\u7269\u7684\u6279\u51c6\u7ee7\u7eed\u5c06\u662f\u5728\u80bf\u7624\u5b66\u91cd\u8981\u53d1\u5c55\uff0c\u201d \u201cCobas EGFR\u7a81\u53d8\u6d4b\u8bd5v2\u7684\u53ef\u4f9b\u5229\u7528\u7b26\u5408\u8fd9\u4e2a\u91cd\u8981EGFR\u57fa\u56e0\u7a81\u53d8\u68c0\u6d4b\u7684\u9700\u8981\uff0c\u5b83\u53ef\u80fd\u6539\u53d8\u6cbb\u7597\u6709\u6548\u6027\u3002\u201d\u7a81\u7834\u6027\u6cbb\u7597\uff0c\u4f18\u5148\u5ba1\u8bc4\u548c\u5b64\u513f\u836f\u7269\u3002\u52a0\u5feb\u6279\u51c6\u7a0b\u5e8f<\/p>\n\n\n\n

\u8fd9\u4e9b\u91cd\u70b9\u4e0d\u5305\u62ec\u5b89\u5168\u548c\u6709\u6548\u4f7f\u7528TAGRISSO\u6240\u9700\u6240\u6709\u8d44\u6599\u3002\u8bf7\u53c2\u9605TAGRISSO\u5b8c\u6574\u5904\u65b9\u8d44\u6599\u3002<\/p>\n\n\n\n

TAGRISSO\u2122(osimertinib)\u7247\uff0c\u4e3a\u53e3\u670d\u4f7f\u7528<\/strong><\/p>\n\n\n\n

\u7f8e\u56fd\u521d\u6b21\u6279\u51c6\uff1a2015<\/p>\n\n\n\n

\u9002\u5e94\u8bc1\u548c\u7528\u9014<\/strong><\/p>\n\n\n\n

TAGRISSO\u662f\u4e00\u79cd\u6fc0\u9176\u6291\u5236\u5242\u9002\u7528\u4e3athe of\u6709\u8f6c\u79fb\u8868\u76ae\u751f\u957f\u56e0\u5b50\u53d7\u4f53(EGFR)\u5f53\u7528FDA-\u6279\u51c6\u7684\u6d4b\u8bd5\u88ab\u68c0\u6d4b\u5230T790M\u7a81\u53d8-\u9633\u6027\u975e\u5c0f\u7ec6\u80de\u80ba\u764c(NSCLC)\uff0c\u60a3\u8005\u7528EGFR TKI\u6cbb\u7597\u6216\u540e\u5df2\u8fdb\u5c55\u60a3\u8005\u7684\u6cbb\u7597\u3002(1)<\/p>\n\n\n\n

\u6b64\u9002\u5e94\u8bc1\u662f\u6839\u636e\u80bf\u7624\u53cd\u5e94\u7387\u548c\u53cd\u5e94\u65f6\u95f4\u5728\u52a0\u5feb\u5ba1\u6279\u7a0b\u5e8f\u4e0b\u88ab\u6279\u51c6\u3002\u7ee7\u7eed\u6279\u51c6\u8fd9\u4e2a\u9002\u5e94\u8bc1\u53ef\u80fd\u53d6\u51b3\u4e8e\u5728\u9a8c\u8bc1\u6027\u8bd5\u9a8c\u4e2d\u4e34\u5e8a\u83b7\u76ca\u7684\u786e\u8bc1\u548c\u63cf\u8ff0\u3002(1)<\/p>\n\n\n\n

\u5242\u91cf\u548c\u7ed9\u836f\u65b9\u6cd5<\/strong><\/p>\n\n\n\n

\u2474\u5728\u7528TAGRISSO\u5f00\u59cb\u6cbb\u7597\u524d\u786e\u8bc1\u5728\u80bf\u7624\u6807\u672c\u4e2dT790M\u7a81\u53d8\u7684\u5b58\u5728\u3002(2.1)<\/p>\n\n\n\n

\u2475 \u53ea80 mg\u53e3\u670d\u6bcf\u59291\u6b21\uff0c\u6709\u98df\u7269\u6216\u65e0\u98df\u7269\u3002(2.2)<\/p>\n\n\n\n

\u5242\u578b\u548c\u89c4\u683c\uff1a80 mg\u548c40 mg(3)<\/p>\n\n\n\n

\u7981\u5fcc\u8bc1<\/p>\n\n\n\n

\u65e0\u3002(4)<\/p>\n\n\n\n

\u3000\u3000\u8b66\u544a\u548c\u6ce8\u610f\u4e8b\u9879<\/strong><\/p>\n\n\n\n

\u2474 \u95f4\u8d28\u6027\u80ba\u75c5(ILD)\/\u80ba\u708e\uff1a\u53d1\u751f\u57283.3%\u60a3\u8005\u3002\u5728\u88ab\u8bca\u65ad\u6709ILD\/\u80ba\u708e\u60a3\u8005\u4e2d\u6c38\u4e45\u5730\u7ec8\u6b62TAGRISSO\u3002(5.1)<\/p>\n\n\n\n

\u2475 QTc\u95f4\u671f\u5ef6\u957f\uff1a\u5728\u6709QTc\u5ef6\u957f\u75c5\u53f2\u6216\u503e\u5411\u60a3\u8005\u76d1\u89c6\u5fc3\u7535\u56fe\u548c\u7535\u89e3\u8d28\uff0c\u6216\u6b63\u5728\u670d\u7528\u5df2\u77e5\u5ef6\u957fQTc\u95f4\u671f\u836f\u7269\u60a3\u8005. \u4e0d\u7ed9\u7136\u540e\u5728\u51cf\u4f4e\u5242\u91cf\u91cd\u65b0\u5f00\u59cb\u6216\u6c38\u4e45\u5730\u7ec8\u6b62TAGRISSO\u3002(2.4\uff0c5.2)<\/p>\n\n\n\n

\u2476 \u5fc3\u808c\u75c5\u53d8\uff1a\u53d1\u751f\u57281.4%\u60a3\u8005\u3002\u6cbb\u7597\u524d\u8bc4\u4f30\u5de6\u5ba4\u5c04\u8840\u529f\u80fd(LVEF)\u548c\u7136\u540e\u5176\u540e\u6bcf3\u4e2a\u6708 \u3002(2.4\uff0c5.3)<\/p>\n\n\n\n

\u2477 \u80da\u80ce-\u80ce\u513f\u6bd2\u6027\uff1aTAGRISSO\u53ef\u80fd\u81f4\u80ce\u513f\u5371\u5bb3\u3002\u5fe0\u544a\u5bf9\u80ce\u513f\u6f5c\u5728\u98ce\u9669\u5973\u6027\u548c\u7528TAGRISSO\u6cbb\u7597\u671f\u95f4\u548c\u6700\u540e\u5242\u91cf\u540e\u51716\u5468\u4f7f\u7528\u6709\u6548\u907f\u5b55\u3002\u5fe0\u544a\u7537\u6027TAGRISSO\u672b\u6b21\u5242\u91cf\u540e\u4f7f\u7528\u6709\u6548\u907f\u5b55\u51714\u4e2a\u6708.(5.3\uff0c8.1\uff0c8.3)<\/p>\n\n\n\n

\u4e0d\u826f\u53cd\u5e94<\/strong><\/p>\n\n\n\n

\u6700\u5e38\u89c1\u4e0d\u826f\u53cd\u5e94(\u226525%)\u662f\u8179\u6cfb\uff0c\u76ae\u75b9\uff0c\u5e72\u76ae\u80a4\uff0c\u548c\u6307\u7532\u6bd2\u6027\u3002(6.1)<\/p>\n\n\n\n

\u62a5\u544a\u6000\u7591\u4e0d\u826f\u53cd\u5e94\uff0c\u8054\u7cfbAstraZeneca\u7535\u8bdd1-800-236-9933\u6216www.TAGRISSO.com\u6216FDA\u7535\u8bdd1-800-FDA-1088\u6216www.fda.gov\/medwatch\u3002<\/p>\n\n\n\n

\u836f\u7269\u76f8\u4e92\u4f5c\u7528<\/strong><\/p>\n\n\n\n

\u2474 \u5f3aCYP3A\u6291\u5236\u5242\uff1a\u5982\u53ef\u80fd\u907f\u514d\u540c\u65f6\u7ed9\u836f\u4e0eTAGRISSO\u3002\u5982\u65e0\u53e6\u5916\u5b58\u5728\uff0c\u5e94\u88ab\u5bc6\u5207\u76d1\u89c6\u6bd2\u6027\u5f81\u8c61\u60a3\u8005\u3002(7.1)<\/p>\n\n\n\n

\u2475 \u5f3aCYP3A\u8bf1\u5bfc\u5242\uff1a\u5982\u53ef\u80fd\u907f\u514d\u56e0\u4e3a\u540c\u65f6\u4f7f\u7528\u53ef\u80fd\u51cf\u4f4eosimertinib\u8840\u6d46\u6d53\u5ea6\u3002(7.1)<\/p>\n\n\n\n

\u5728\u7279\u5f02\u6027\u4eba\u7fa4\u4e2d\u4f7f\u7528<\/p>\n\n\n\n

\u54fa\u4e73\uff1a\u4e0d\u8981\u54fa\u4e73\u5582\u517b\u3002(8.2)<\/p>\n\n\n\n

\u5b8c\u6574\u5904\u65b9\u8d44\u6599<\/strong><\/p>\n\n\n\n

1 \u9002\u5e94\u8bc1\u548c\u7528\u9014<\/strong><\/p>\n\n\n\n

TAGRISSO\u662f\u9002\u7528\u4e3athe \u6cbb\u7597 of\u60a3\u8005\u6709\u8f6c\u79fb\u8868\u76ae\u751f\u957f\u56e0\u5b50\u53d7\u4f53(EGFR) \u7528\u4e00\u4e2aFDA-\u6279\u51c6\u7684\u6d4b\u8bd5\u68c0\u51fa\u7684T790M\u7a81\u53d8-\u9633\u6027\u975e\u5c0f\u7ec6\u80de\u80ba\u764c(NSCLC)\uff0c\u60a3\u8005\u5bf9\u7528EGFR\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242(TKI)\u6cbb\u7597\u5df2\u6216\u540e\u8fdb\u5c55\u3002<\/p>\n\n\n\n

\u6b64\u9002\u5e94\u8bc1\u662f\u5728\u52a0\u5feb\u5ba1\u6279\u7a0b\u5e8f\u4e0b\u6839\u636e\u5bf9\u80bf\u7624\u53cd\u5e94\u7387\u548c\u53cd\u5e94\u65f6\u95f4\u6279\u51c6\u7684[\u89c1\u4e34\u5e8a\u7814\u7a76(14)]\u3002\u7ee7\u7eed\u6279\u51c6\u8fd9\u4e2a\u9002\u5e94\u8bc1\u53ef\u80fd\u53d6\u51b3\u4e8e\u5728\u9a8c\u8bc1\u6027\u8bd5\u9a8c\u4e2d\u4e34\u5e8a\u83b7\u76ca\u7684\u786e\u8bc1\u548c\u63cf\u8ff0\u3002<\/p>\n\n\n\n

2 \u5242\u91cf\u548c\u7ed9\u836f\u65b9\u6cd5<\/strong><\/p>\n\n\n\n

2.1 \u60a3\u8005\u9009\u62e9<\/strong><\/p>\n\n\n\n

\u7528TAGRISSO\u5f00\u59cb\u6cbb\u7597\u524d\u786e\u8bc1\u5728\u80bf\u7624\u6807\u672c\u4e2d\u5b58\u5728T790M EGFR\u7a81\u53d8[\u89c1\u9002\u5e94\u8bc1\u548c\u7528\u9014(1)\u548c\u4e34\u5e8a\u7814\u7a76(14)]\u3002\u5173\u4e8eFDA-\u6279\u51c6\u4e3a\u68c0\u6d4bT790M\u7a81\u53d8\u6d4b\u8bd5\u4fe1\u606f\u5728http:\/\/www.fda.gov\/companiondiagnostics\u53ef\u5f97\u5230\u3002<\/p>\n\n\n\n

2.2 \u63a8\u8350\u5242\u91cf\u65b9\u6848<\/strong><\/p>\n\n\n\n

TAGRISSO\u7684\u63a8\u8350\u5242\u91cf\u662f80 mg\u7247\u4e00\u59291\u6b21\u76f4\u81f3\u75be\u75c5\u8fdb\u5c55\u6216\u4e0d\u53ef\u63a5\u53d7\u6bd2\u6027\u3002TAGRISSO\u53ef\u6709\u6216\u65e0\u98df\u7269\u88ab\u670d\u7528.<\/p>\n\n\n\n

\u5982\u7f3a\u5931\u4e00\u5242TAGRISSO\u3002\u4e0d\u8981\u7ec4\u6210\u7f3a\u5931\u5242\u91cf\u548c\u670d\u7528\u5982\u65f6\u95f4\u8868\u4e0b\u4e00\u6b21\u5242\u91cf\u3002<\/p>\n\n\n\n

2.3 \u6709\u541e\u54bd\u56fa\u4f53\u56f0\u96be\u7684\u60a3\u8005\u7684\u7ed9\u836f<\/strong><\/p>\n\n\n\n

\u53ea\u7528\u975e\u78b3\u9178\u6c34\u5206\u6563\u7247\u57284\u6c64\u5319(\u7ea650 mL)\u3002\u6405\u62cc\u76f4\u81f3\u7247\u88ab\u5b8c\u5168\u5206\u6563\u548c\u7acb\u5373\u541e\u54bd\u6216\u901a\u8fc7\u9f3b\u54bd\u7ba1\u7ed9\u4e88\u3002\u5236\u5907\u671f\u95f4\u4e0d\u8981\u538b\u788e\uff0c\u70ed\uff0c\u6216\u8d85\u58f0\u3002\u75284\u81f38\u76ce\u53f8\u6c34\u51b2\u6d17\u5bb9\u5668\u548c\u7acb\u5373\u996e\u6216\u901a\u8fc7\u9f3b\u54bd\u7ba1\u7ed9\u4e88[\u89c1\u4e34\u5e8a\u836f\u7406\u5b66(12.3)].<\/p>\n\n\n\n

2.4\u5bf9\u4e0d\u826f\u53cd\u5e94\u5242\u91cf\u8c03\u6574<\/strong><\/p>\n\n\n\n

3 \u5242\u578b\u548c\u89c4\u683c<\/strong><\/p>\n\n\n\n

80 mg\u7247\uff1a\u7c73\u8272\uff0c\u692d\u5706\u5f62\u548c\u53cc\u51f8\u7247\u5728\u4e00\u4fa7\u6807\u8bb0\u6709\u201cAZ 80\u201d\u548c\u53cd\u9762\u5e73\u5766\u3002<\/p>\n\n\n\n

40 mg\u7247\uff1a\u7c73\u8272\uff0c\u5706\u548c\u53cc\u51f8\u7247\u5728\u4e00\u4fa7\u6807\u8bb0\u6709\u201cAZ 40\u201d\u548c\u53cd\u9762\u5e73\u5766\u3002<\/p>\n\n\n\n

4 \u7981\u5fcc\u8bc1\uff1a\u65e0\u3002<\/strong><\/p>\n\n\n\n

5 \u8b66\u544a\u548c\u6ce8\u610f\u4e8b\u9879<\/strong><\/p>\n\n\n\n

5.1 \u95f4\u8d28\u6027\u80ba\u75be\u75c5\/\u80ba\u708e<\/strong><\/p>\n\n\n\n

\u8de8\u8d8a\u4e34\u5e8a\u8bd5\u9a8c\uff0cTAGRISSO\u6cbb\u7597\u60a3\u8005(n=813)\u53d1\u751f\u57283.3%(n=27)\u95f4\u8d28\u6027\u80ba\u75c5(ILD)\/\u80ba\u708e;0.5%(n=4)\u662f\u81f4\u547d\u6027\u3002<\/p>\n\n\n\n

\u4e0d\u7ed9TAGRISSO\u548c\u53ca\u65f6\u7814\u7a76\u5728\u4efb\u4f55\u5b58\u5728\u547c\u5438\u75c7\u72b6\u6076\u5316\u53ef\u80fd\u6307\u793aILD\u60a3\u8005(\u5982\uff0c\u547c\u5438\u56f0\u96be\uff0c\u54b3\u55fd\u548c\u53d1\u70ed)\u3002\u5982\u786e\u8bc1ILD\u6c38\u4e45\u5730\u7ec8\u6b62TAGRISSO[\u89c1\u5242\u91cf\u548c\u7ed9\u836f\u65b9\u6cd5(2.4)\u548c\u4e0d\u826f\u53cd\u5e94(6)]\u3002<\/p>\n\n\n\n

5.2 QTc\u95f4\u671f\u5ef6\u957f<\/strong><\/p>\n\n\n\n

\u5728\u7528TAGRISSO\u6cbb\u7597\u60a3\u8005\u4e2d\u53d1\u751f\u6821\u6b63\u5fc3\u7387QT(QTc)\u95f4\u671f\u5ef6\u957f\u3002\u5728\u7814\u7a761\u548c\u7814\u7a762\u7684411\u60a3\u8005\uff0c\u53d1\u73b01\u4f8b\u60a3\u8005(0.2%)\u6709QTc\u5927\u4e8e50 0 msec\uff0c\u548c11\u4f8b\u60a3\u8005(2.7%)\u6709\u4ece\u57fa\u7ebfQTc\u589e\u52a0\u5927\u4e8e60 msec[\u89c1\u4e34\u5e8a\u836f\u7406\u5b66(12.2)]\u3002<\/p>\n\n\n\n

\u5728\u7814\u7a761\u548c2\u4e2d\uff0c\u6709\u57fa\u7ebfQTc 470 msec\u6216\u66f4\u5927\u60a3\u8005\u88ab\u6392\u9664\u3002\u5728\u6709\u5148\u5929\u6027\u957fQTc\u7efc\u5408\u75c7\uff0c\u5145\u8840\u6027\u5fc3\u529b\u8870\u7aed\uff0c\u7535\u89e3\u8d28\u5f02\u5e38\uff0c\u6216\u670d\u7528\u5df2\u77e5\u5ef6\u957fQTc\u95f4\u671f\u60a3\u8005\u8fdb\u884c\u5b9a\u671f\u76d1\u89c6ECGs\u548c\u7535\u89e3\u8d28\u3002\u53d1\u751fQTc\u95f4\u671f\u5ef6\u957f\u4e0e\u5a01\u80c1\u751f\u547d\u5fc3\u5f8b\u4e0d\u9f50\u7684\u4f53\u5f81\/\u75c7\u72b6\u60a3\u8005\u6c38\u4e45\u5730\u7ec8\u6b62TAGRISSO[\u89c1\u5242\u91cf\u548c\u7ed9\u836f\u65b9\u6cd5(2.4)]\u3002<\/p>\n\n\n\n

5.3 \u5fc3\u808c\u75c5\u53d8<\/strong><\/p>\n\n\n\n

\u8de8\u8d8a\u4e34\u5e8a\u8bd5\u9a8c\uff0c\u5fc3\u808c\u75c5\u53d8(\u88ab\u5b9a\u4e49\u4e3a\u5fc3\u8870\uff0c\u80ba\u6c34\u80bf\uff0c\u5c04\u8840\u529f\u80fd\u51cf\u4f4e\u6216\u5e94\u6fc0\u5fc3\u808c\u75c5\u53d8) TAGRISSO\u6cbb\u7597\u60a3\u8005(n=813)\u53d1\u751f1.4%(n=11);0.2%(n=2)\u4e3a\u81f4\u547d\u6027\u3002<\/p>\n\n\n\n

\u5728\u7814\u7a761\u548c\u7814\u7a762\u4e2d\uff0c\u5de6\u5ba4\u5c04\u8840\u529f\u80fd(LVEF)\u4e0b\u964d >10%\u548c\u57282.4%(9\/375)\u6709\u57fa\u7ebf\u548c\u81f3\u5c111\u6b21\u968f\u8bbfLVEF\u8bc4\u4f30\u60a3\u8005\u53d1\u751f\u4e0b\u964d\u81f3<50%\u3002<\/p>\n\n\n\n

TAGRISSO\u7684\u5f00\u59cb\u524d\u548c\u7136\u540e\u5f53\u7528\u6cbb\u7597\u57283\u4e2a\u6708\u95f4\u9694\u901a\u8fc7\u8d85\u58f0\u5fc3\u52a8\u56fe\u6216\u591a\u95f8\u95e8\u5f0f\u9020\u5f71(MUGA)\u626b\u63cf\u8bc4\u4f30LVEF\u3002\u5982\u5c04\u8840\u5206\u91cf\u4ece\u6cbb\u7597\u524d\u503c\u51cf\u4f4e10%\u548c\u662f\u4f4e\u4e8e50\u4e0d\u7ed9\u7528TAGRISSO\u6cbb\u7597\u3002\u5bf9\u57284\u5468\u5185\u4e0d\u89e3\u51b3\u75c7\u72b6\u6027\u5145\u8840\u6027\u5fc3\u8870\u6216\u6301\u7eed\uff0c\u65e0\u75c7\u72b6LV\u529f\u80fd\u969c\u788d\uff0c\u6c38\u4e45\u5730\u7ec8\u6b62TAGRISSO[\u89c1\u5242\u91cf\u548c\u7ed9\u836f\u65b9\u6cd5(2.4)]\u3002<\/p>\n\n\n\n

5.4 \u80da\u80ce-\u80ce\u513f\u6bd2\u6027<\/strong><\/p>\n\n\n\n

\u6839\u636e\u6765\u81ea\u52a8\u7269\u7814\u7a76\u6570\u636e\u548c\u5176\u4f5c\u7528\u673a\u5236\uff0c\u5f53\u7ed9\u4e88\u4e00\u4f4d\u598a\u5a20\u5987\u5973TAGRISSO\u53ef\u80fd\u81f4\u80ce\u513f\u5371\u5bb3\u3002\u5728\u52a8\u7269\u751f\u6b96\u7814\u7a76\u4e2d\uff0c\u5f53\u65e9\u671f\u53d1\u80b2\u671f\u95f4\u7ed9\u4e88\u5728\u5242\u91cf\u66b4\u9732\u4e3a\u4eba\u63a8\u8350\u5242\u91cf\u66b4\u9732\u76841.5\u500d\u65f6osimertinib\u81f4\u690d\u5165\u540e\u80ce\u513f\u6d41\u4ea7\u3002\u5f53\u96c4\u6027\u5728\u5904\u7406\u524d\u4e0e\u672a\u5904\u7406\u96cc\u6027\u4ea4\u914d\uff0c\u5728\u8840\u6d46\u66b4\u9732\u4e3a\u60a3\u8005\u572880 mg\u5242\u91cf\u6c34\u5e73\u89c2\u5bdf\u5230\u66b4\u9732\u7684\u7ea60.5-\u500d\u6c34\u5e73\u65f6\u6709\u5728\u690d\u5165\u524d\u80da\u80ce\u4e22\u5931\u6709\u589e\u52a0\u3002\u5fe0\u544a\u598a\u5a20\u5987\u5973\u5bf9\u80ce\u513f\u6f5c\u5728\u98ce\u9669\u3002<\/p>\n\n\n\n

\u5fe0\u544a\u751f\u6b96\u6f5c\u80fd\u5973\u6027\u7528TAGRISSO\u6cbb\u7597\u671f\u95f4\u548c\u6700\u540e\u5242\u91cf\u540e\u51716\u5468\u4f7f\u7528\u6709\u6548\u907f\u5b55\u3002\u5fe0\u544a\u6709\u751f\u6b96\u6f5c\u80fd\u5973\u6027\u4f34\u4fa3\u7537\u6027\u5bf9\u6700\u540e\u5242\u91cf\u540e\u51714\u4e2a\u6708\u4f7f\u7528\u6709\u6548\u907f\u5b55[\u89c1\u5728\u7279\u5f02\u6027\u4eba\u7fa4\u4e2d\u4f7f\u7528(8.1)\uff0c(8.3)\u548c\u4e34\u5e8a\u836f\u7406\u5b66(12.3)]\u3002<\/p>\n\n\n\n

6 \u4e0d\u826f\u53cd\u5e94<\/strong><\/p>\n\n\n\n

\u5728\u8bf4\u660e\u4e66\u5176\u4ed6\u8282\u66f4\u8be6\u7ec6\u8ba8\u8bba\u4ee5\u4e0b\u4e0d\u826f\u53cd\u5e94\uff1a<\/p>\n\n\n\n

\u95f4\u8d28\u6027\u80ba\u75be\u75c5\/\u80ba\u708e[\u89c1\u8b66\u544a\u548c\u6ce8\u610f\u4e8b\u9879(5.1)]<\/p>\n\n\n\n

QTc\u95f4\u671f\u5ef6\u957f[\u89c1\u8b66\u544a\u548c\u6ce8\u610f\u4e8b\u9879(5.2)]<\/p>\n\n\n\n

6.1 \u4e34\u5e8a\u7814\u7a76\u7ecf\u9a8c<\/strong><\/p>\n\n\n\n

\u56e0\u4e3a\u4e34\u5e8a\u8bd5\u9a8c\u662f\u5728\u5e7f\u6cdb\u4e0d\u540c\u60c5\u51b5\u4e0b\u8fdb\u884c\u7684\uff0c\u4e34\u5e8a\u8bd5\u9a8c\u89c2\u5bdf\u5230\u4e0d\u826f\u53cd\u5e94\u7387\u4e0d\u80fd\u4e0e\u53e6\u4e00\u79cd\u836f\u4e34\u5e8a\u8bd5\u9a8c\u53d1\u751f\u7387\u76f4\u63a5\u6bd4\u8f83\u800c\u4e14\u53ef\u80fd\u4e0d\u53cd\u6620\u5b9e\u8df5\u4e2d\u89c2\u5bdf\u5230\u7684\u53d1\u751f\u7387\u3002<\/p>\n\n\n\n

\u4e0b\u9762\u63cf\u8ff0\u6570\u636e\u53cd\u6620\u66b4\u9732\u81f3TAGRISSO(80 mg\u6bcf\u5929)\u5728\u4e24\u9879\u5355\u81c2\u7814\u7a76\uff0c\u7814\u7a761\u548c\u7814\u7a762\u4e2d411\u4f8b\u6709EGFR T790M\u7a81\u53d8-\u9633\u6027\u975e\u5c0f\u7ec6\u80de\u80ba\u764c\u63a5\u53d7\u4ee5\u524dEGFR TKI\u6cbb\u7597\u60a3\u8005\u3002\u60a3\u8005\u6709\u4e00\u4e2a\u8fc7\u53bbILD\u6216\u8f90\u5c04\u80ba\u708e\u533b\u7597\u53f2\u9700\u8981\u753e\u4f53\u6cbb\u7597\uff0c\u4e25\u91cd\u5fc3\u5f8b\u4e0d\u9f50\u6216\u57fa\u7ebfQTc\u95f4\u671f\u5927\u4e8e470 ms\u4ece\u7814\u7a761\u548c\u7814\u7a762\u88ab\u6392\u9664\u3002\u60a3\u8005\u57fa\u7ebf\u548c\u75be\u75c5\u7279\u5f81\u4e3a\uff1a\u4e2d\u4f4d\u5e74\u9f8463\u5c81\uff0c13%\u60a3\u8005\u4e3a\u226575\u5c81\uff0c\u5973\u6027(68%)\uff0c\u767d\u79cd\u4eba(36%)\uff0c\u4e9a\u88d4(60%)\uff0c\u8f6c\u79fb(96%)\uff0c\u8111\u8f6c\u79fb\u90e8\u4f4d(39%)\uff0c\u4e16\u754c\u536b\u751f\u7ec4\u7ec7(WHO)\u6027\u80fd\u72b6\u6001 0(37%)\u62161(63%)\uff0c1\u4ee5\u524d\u7ebf\u6cbb\u7597[\u53ea\u6709EGFR-TKI\u6cbb\u7597\uff0c\u4e8c\u7ebf\uff0c\u5316\u7597\u672a\u6cbb\u7597\u8fc7(31%)]\uff0c2\u6216\u66f4\u591a\u4ee5\u524d\u7ebf\u6cbb\u7597(69%)\u3002411\u4f8b\u60a3\u8005\u4e2d\uff0c333\u4f8b\u60a3\u8005\u88ab\u66b4\u9732\u81f3TAGRISSO\u5171\u81f3\u5c116\u4e2a\u6708; 97\u4f8b\u60a3\u8005\u88ab\u66b4\u9732\u81f3\u5171\u81f3\u5c119\u4e2a\u6708; \u4f46\u662f\u6ca1\u6709\u60a3\u8005\u88ab\u66b4\u9732\u81f3TAGRISSO\u517112\u4e2a\u6708\u3002<\/p>\n\n\n\n

\u5728\u7814\u7a761\u548c2\u4e2d\uff0c\u5728TAGRISSO-\u6cbb\u7597\u60a3\u8005\u89c2\u5bdf\u5230\u6700\u5e38\u89c1(>20%)\u4e0d\u826f\u53cd\u5e94(\u6240\u6709\u7ea7\u522b)\u662f\u8179\u6cfb(42%)\uff0c\u76ae\u75b9(41%)\uff0c\u5e72\u76ae\u80a4(31%)\uff0c\u548c\u6307\u7532\u6bd2\u6027(25%)\u3002\u7528TAGRISSO\u6cbb\u7597\u60a3\u8005\u5242\u91cf\u51cf\u4f4e\u53d1\u751f4.4%\u3002\u6700\u9891\u7e41\u4e0d\u826f\u53cd\u5e94\u5bfc\u81f4\u5242\u91cf\u51cf\u4f4e\u6216\u4e2d\u65ad\u662f\uff1a\u5fc3\u7535\u56feQTc\u5ef6\u957f(2.2%)\u548c\u4e2d\u6027\u7c92\u7ec6\u80de\u51cf\u5c11(1.9%)\u3002\u62a5\u9053\u4e25\u91cd\u4e0d\u826f\u53cd\u5e94\u57282%\u6216\u66f4\u591a\u60a3\u8005\u4e3a\u80ba\u708e\u548c\u80ba\u6813\u585e\u3002\u7528TAGRISSO\u6cbb\u7597\u67094\u4f8b\u60a3\u8005(1%)\u53d1\u751fILD\/\u80ba\u708e\u81f4\u547d\u6027\u4e0d\u826f\u53cd\u5e94\u3002\u5176\u4ed6\u81f4\u547d\u6027\u4e0d\u826f\u53cd\u5e94\u53d1\u751f\u8d85\u8fc71\u4f8b\u60a3\u8005\u5305\u62ec\u80ba\u708e(4\u4f8b\u60a3\u8005)\u548cCVA\/\u8111\u51fa\u8840(2\u4f8b\u60a3\u8005)\u3002\u57285.6%\u7528TAGRISSO\u6cbb\u7597\u60a3\u8005\u7531\u4e8e\u4e0d\u826f\u53cd\u5e94\u53d1\u751f\u7ec8\u6b62\u6cbb\u7597\u3002\u5bfc\u81f4\u7ec8\u6b62\u6700\u9891\u4e0d\u826f\u53cd\u5e94\u4e3aILD\/\u80ba\u708e\u548c\u8111\u8840\u7ba1\u610f\u5916\/\u6897\u6b7b\u3002<\/p>\n\n\n\n

7 \u836f\u7269\u76f8\u4e92\u4f5c\u7528<\/strong><\/p>\n\n\n\n

\u672a\u66fd\u7528TAGRISSO\u4e0eCYP\u9176\u548c\u8f6c\u8fd0\u86cb\u767d\u7684\u6291\u5236\u5242\uff0c\u8bf1\u5bfc\u5242\u6216\u5e95\u7269\u8fdb\u884c\u836f\u7269\u76f8\u4e92\u4f5c\u7528\u7814\u7a76\u3002<\/p>\n\n\n\n

7.1 \u5176\u4ed6\u836f\u7269\u5bf9Osimertinib\u7684\u5f71\u54cd<\/strong><\/p>\n\n\n\n

\u5f3aCYP3A\u6291\u5236\u5242<\/strong><\/p>\n\n\n\n

\u907f\u514dTAGRISSO\u4e0e\u5f3aCYP3A\u6291\u5236\u5242\u7684\u540c\u65f6\u7ed9\u836f\uff0c\u5305\u62ec\u5927\u73af\u5185\u916f\u7c7b\u6297\u751f\u7d20(\u5982\uff0c\u6cf0\u5229\u9709\u7d20[telithromycin])\uff0c\u6297\u771f\u83cc\u836f(\u5982\uff0c\u610f\u66f2\u5eb7\u5511[itraconazole])\uff0c\u6297\u75c5\u6bd2\u836f\uff0c\u5229\u6258\u90a3\u97e6[ritonavir])\uff0c\u5948\u6cd5\u5511\u916e[nefazodone]\uff0c\u56e0\u4e3a\u5f3aCYP3A\u6291\u5236\u5242\u7684\u540c\u65f6\u4f7f\u7528\u53ef\u80fd\u589e\u52a0osimertinib\u8840\u6d46\u6d53\u5ea6\u3002\u5982\u65e0\u5176\u4ed6\u53e6\u5916\u5b58\u5728\uff0c\u4e25\u5bc6\u76d1\u89c6\u60a3\u8005\u5bf9TAGRISSO\u7684\u4e0d\u826f\u53cd\u5e94[\u89c1\u5242\u91cf\u548c\u7ed9\u836f\u65b9\u6cd5(2.4)\u548c\u4e34\u5e8a\u836f\u7406\u5b66(12.3)]\u3002<\/p>\n\n\n\n

\u5f3aCYP3A\u8bf1\u5bfc\u5242<\/strong><\/p>\n\n\n\n

\u907f\u514dTAGRISSO\u4e0e\u5f3aCYP3A\u8bf1\u5bfc\u5242\u7684\u540c\u65f6\u7ed9\u836f(\u5982\uff0c\u82ef\u59a5\u82f1\u94a0[phenytoin]\uff0c\u5229\u798f\u5e73[rifampicin]\uff0c\u5361\u9a6c\u897f\u5e73[carbamazepine]\uff0c\u5723\u7ea6\u7ff0\u8349[St. John\u2019s Wort])\u56e0\u4e3a\u5f3aCYP3A\u8bf1\u5bfc\u5242\u53ef\u80fd\u51cf\u4f4e osimertinib\u8840\u6d46\u6d53\u5ea6[\u89c1\u4e34\u5e8a\u836f\u7406\u5b66(12.3)]\u3002<\/p>\n\n\n\n

7.2 Osimertinib\u5bf9\u5176\u4ed6\u836f\u7269\u7684\u5f71\u54cd<\/strong><\/p>\n\n\n\n

\u907f\u514d\u7684\u540c\u65f6\u7ed9\u836fTAGRISSO\u4e0e\u836f\u7269\u662fCYP3A\uff0c\u4e73\u764c\u8010\u836f\u6027\u86cb\u767d(BCRP)\uff0c\u4e0eCYP1A2\u6709\u72ed\u7a84\u6cbb\u7597\u6307\u6570\u7684\u654f\u611f\u5e95\u7269\uff0c\u5305\u62ec\u4f46\u4e0d\u9650\u4e8e\u82ac\u592a\u5c3c[fentanyl]\uff0c\u73af\u5b62\u9709\u7d20[cyclosporine]\uff0c\u594e\u5c3c\u4e01[quinidine]\uff0c\u9ea6\u89d2\u751f\u7269\u78b1[ergot alkaloids]\uff0c\u82ef\u59a5\u82f1\u94a0\uff0c\u5361\u9a6c\u897f\u5e73\uff0c\u56e0\u4e3aosimertinib\u53ef\u80fd\u589e\u52a0\u6216\u51cf\u4f4e\u8fd9\u4e9b\u836f\u7269\u7684\u8840\u6d46\u6d53\u5ea6[\u89c1\u4e34\u5e8a\u836f\u7406\u5b66(12.3)]\u3002<\/p>\n\n\n\n

8 \u5728\u7279\u5f02\u6027\u4eba\u7fa4\u4e2d\u4f7f\u7528<\/strong><\/p>\n\n\n\n

8.1 \u598a\u5a20<\/strong><\/p>\n\n\n\n

\u98ce\u9669\u603b\u7ed3<\/strong><\/p>\n\n\n\n

\u6839\u636e\u6765\u81ea\u52a8\u7269\u7814\u7a76\u6570\u636e\u548c\u5176\u4f5c\u7528\u673a\u5236\uff0c\u5f53\u7ed9\u4e88\u598a\u5a20\u5987\u5973TAGRISSO\u53ef\u80fd\u81f4\u80ce\u513f\u5371\u5bb3\u3002\u5bf9TAGRISSO\u5728\u598a\u5a20\u5987\u5973\u4f7f\u7528\u6ca1\u6709\u53ef\u5f97\u5230\u6570\u636e\u3002\u598a\u5a20\u5927\u9f20\u7ed9\u4e88osimertinib\u5728\u8840\u6d46\u66b4\u9732\u4e3a\u63a8\u8350\u4eba\u5242\u91cf1.5\u500d\u65f6\u4f34\u968f\u80da\u80ce\u81f4\u6b7b\u548c\u51cf\u4f4e[\u89c1\u6570\u636e]\u3002\u5fe0\u544a\u598a\u5a20\u5987\u5973\u5bf9\u80ce\u513f\u6f5c\u5728\u98ce\u9669\u3002<\/p>\n\n\n\n

\u5728\u7f8e\u56fd\u4e00\u822c\u4eba\u7fa4\uff0c\u4e3b\u8981\u51fa\u751f\u7f3a\u9677\u548c\u4e34\u5e8a\u4e0a\u8ba4\u53ef\u598a\u5a20\u4e2d\u6d41\u4ea7\u7684\u4f30\u7b97\u80cc\u666f\u98ce\u9669\u5206\u522b\u4e3a2%\u81f34%\u548c15%\u81f320%\u3002<\/p>\n\n\n\n

\u6570\u636e<\/strong><\/p>\n\n\n\n

\u52a8\u7269\u6570\u636e<\/strong><\/p>\n\n\n\n

\u5f53\u80da\u80ce\u690d\u5165\u524d\u81f3\u5668\u5b98\u5f62\u6210\u671f\u7ed3\u675f\u65f6(\u6000\u5b55\u7b2c2-20\u5929)\u7ed9\u4e88\u598a\u5a20\u5927\u9f20\u5728\u5242\u91cf20 mg\/kg\/day\uff0c\u4ea7\u751f\u8840\u6d46\u66b4\u9732\u7ea6\u4e34\u5e8a\u66b4\u9732\u76841.5\u500d\uff0cosimertinib\u81f4\u690d\u5165\u540e\u4e22\u5931\u548c\u65e9\u671f\u80da\u80ce\u6b7b\u4ea1\u3002\u5f53\u4ece\u690d\u5165\u81f3\u786c\u816d\u95ed\u5408(\u6000\u5b55\u7b2c6\u81f316\u5929)\u7ed9\u4e88\u598a\u5a20\u5927\u9f20\u5728\u5242\u91cf1 mg\/kg\/day\u548c\u4ee5\u4e0a(\u60a3\u8005\u5728\u7684\u63a8\u8350\u5242\u91cf80 mg\u89c2\u5bdf\u5230AUC\u76840.1-\u500d)\uff0c\u89c2\u5bdf\u5230\u5728\u88ab\u6cbb\u7597\u7a9d\u4e2d\u76f8\u5bf9\u4e8e\u540c\u65f6\u5bf9\u7167\u80ce\u513f\u7578\u5f62\u548c\u53d8\u5f02\u7387\u6a21\u68f1\u4e24\u53ef\u7684\u589e\u52a0\u3002\u5f53\u5728\u5668\u5b98\u5f62\u6210\u671f\u81f3\u54fa\u4e73\u7b2c6\u5929\u7ed9\u4e88\u81f3\u598a\u5a20\u6bcd\u517d\u5728\u5242\u91cf30 mg\/kg\/day\uff0cosimertinib \u81f4\u6574\u7a9d\u4e22\u5931\u548c\u4ea7\u540e\u6b7b\u4ea1\u589e\u52a0\u3002\u5728\u76f8\u540c\u65f6\u95f4\u9636\u6bb5\u5728\u5242\u91cf\u7ed9\u4e88osimertinib 20 mg\/kg\/day\u5bfc\u81f4\u4ea7\u540e\u65b0\u751f\u755c\u6b7b\u4ea1\u589e\u52a0\u4ee5\u53ca\u5728\u51fa\u751f\u65f6\u5747\u6570\u4ed4\u755c\u5728\u54fa\u4e73\u7b2c4\u548c6\u5929\u95f4\u4f53\u91cd\u5e45\u5ea6\u589e\u52a0\u3002<\/p>\n\n\n\n

8.2 \u54fa\u4e73<\/strong><\/p>\n\n\n\n

\u98ce\u9669\u603b\u7ed3<\/strong><\/p>\n\n\n\n

\u6ca1\u6709\u5bf9osimertinib\u5728\u4eba\u4e73\u6c41\u4e2d\u5b58\u5728\uff0cthe effects of osimertinib\u5bf9\u54fa\u4e73\u5582\u517b\u5a74\u513f\u6216\u5bf9\u4e73\u6c41\u4ea7\u751f\u7684\u5f71\u54cd\u7684\u6570\u636e\u3002\u6000\u5b55\u671f\u95f4\u548c\u65e9\u671f\u54fa\u4e73\u7ed9\u4e88\u5927\u9f20\u662f\u4f34\u968f\u4e0d\u826f\u6548\u5e94\uff0c\u5305\u62ec\u51cf\u4f4e\u751f\u957f\u901f\u7387\u548c\u65b0\u751f\u755c\u6b7b\u4ea1[\u89c1\u5728\u7279\u5f02\u6027\u4eba\u7fa4\u4e2d\u4f7f\u7528(8.1)]\u3002\u56e0\u4e3a\u5728\u5bf9\u54fa\u4e73\u5582\u517b\u5a74\u513f\u6765\u81eaosimertinib\u4e25\u91cd\u4e0d\u826f\u53cd\u5e94\u6f5c\u80fd\uff0c\u5fe0\u544a\u6b63\u5728\u54fa\u4e73\u5987\u5973\u7528TAGRISSO\u6cbb\u7597\u671f\u95f4\u548c\u6700\u540e\u5242\u91cf\u540e\u51712\u5468\u4e0d\u8981\u54fa\u4e73\u5582\u517b\u3002<\/p>\n\n\n\n

8.3 \u751f\u6b96\u6f5c\u80fd\u5973\u6027\u548c\u7537\u6027<\/strong><\/p>\n\n\n\n

\u907f\u5b55<\/strong><\/p>\n\n\n\n

\u5973\u6027<\/strong><\/p>\n\n\n\n

\u5fe0\u544a\u751f\u6b96\u6f5c\u80fd\u5973\u6027\u7528TAGRISSO\u6cbb\u7597\u671f\u95f4\u548c\u6700\u540e\u5242\u91cf\u540e\u51716\u5468\u4f7f\u7528\u6709\u6548\u907f\u5b55[\u89c1\u5728\u7279\u5f02\u6027\u4eba\u7fa4\u4e2d\u4f7f\u7528(8.1)]\u3002<\/p>\n\n\n\n

\u7537\u6027<\/strong><\/p>\n\n\n\n

\u5fe0\u544a\u6709\u751f\u6b96\u6f5c\u80fd\u5973\u6027\u4f34\u4fa3\u7537\u6027\u60a3\u8005TAGRISSO\u671f\u95f4\u548c\u6700\u540e\u5242\u91cf\u540e\u51714\u4e2a\u6708\u4f7f\u7528\u6709\u6548\u907f\u5b55[\u89c1\u975e\u4e34\u5e8a\u6bd2\u7406\u5b66(13.1)]\u3002<\/p>\n\n\n\n

\u4e0d\u5b55\u4e0d\u80b2<\/strong><\/p>\n\n\n\n

\u6839\u636e\u52a8\u7269\u7814\u7a76\uff0c\u5728\u751f\u6b96\u6f5c\u80fd\u96cc\u6027\u548c\u96c4\u6027TAGRISSO\u53ef\u80fd\u635f\u5bb3\u751f\u80b2\u529b\u3002\u4e0d\u77e5\u9053\u8fd9\u4e2a\u5bf9\u751f\u80b2\u529b\u5f71\u54cd\u662f\u5426\u53ef\u9006\u6027[\u89c1\u975e\u4e34\u5e8a\u6bd2\u7406\u5b66(13.1)].<\/p>\n\n\n\n

8.4 \u513f\u7ae5\u4f7f\u7528<\/strong><\/p>\n\n\n\n

\u5c1a\u672a\u786e\u5b9a\u5728\u513f\u7ae5\u60a3\u8005\u4e2dTAGRISSO\u7684\u5b89\u5168\u6027\u548c\u6709\u6548\u6027\u3002<\/p>\n\n\n\n

8.5 \u8001\u5e74\u4eba\u4f7f\u7528<\/strong><\/p>\n\n\n\n

\u5728411\u4f8b\u60a3\u8005\u7684TAGRISSO\u4e34\u5e8a\u8bd5\u9a8c\u4e2d187\u4f8b(45%)\u662f65\u5c81\u548c\u4ee5\u4e0a\uff0c\u548c54\u4f8b\u60a3\u8005(13%)\u662f75\u5c81\u548c\u4ee5\u4e0a\u3002\u6839\u636e\u5e74\u9f84\u672a\u89c2\u5bdf\u5230\u6709\u6548\u6027\u4e2d\u603b\u4f53\u5dee\u522b\u3002\u5f00\u62d3\u6027\u5206\u6790\u63d0\u793a65\u5c81\u6216\u4ee5\u4e0a\u60a3\u8005\u5f53\u4e0e\u6bd465\u5c81\u5e74\u8f7b\u60a3\u8005\u6bd4\u8f833\u548c4\u7ea7\u4e0d\u826f\u53cd\u5e94\u53d1\u751f\u7387\u8f83\u9ad8(32%\u76f8\u6bd425%)\u548c\u5bf9\u4e0d\u826f\u53cd\u5e94\u8c03\u6574\u66f4\u9891(23%\u76f8\u6bd417%)\u3002<\/p>\n\n\n\n

8.6 \u80be\u53d7\u635f<\/strong><\/p>\n\n\n\n

\u672a\u8fdb\u884c\u4e13\u95e8\u4e34\u5e8a\u7814\u7a76\u8bc4\u4ef7\u80be\u53d7\u635f\u5bf9osimertinib\u836f\u4ee3\u52a8\u529b\u5b66\u7684\u5f71\u54cd\u3002\u6839\u636e\u7fa4\u4f53\u836f\u4ee3\u52a8\u529b\u5b66\u5206\u6790\uff0c\u5728\u6709\u8f7b\u5ea6[\u808c\u9150\u6e05\u9664\u7387(CLcr)60-89 mL\/min]\u6216\u4e2d\u5ea6(CLcr 30-59 mL\/min)\u80be\u53d7\u635f\u60a3\u8005\u5efa\u8bae\u65e0\u5242\u91cf\u8c03\u6574\u3002\u5bf9\u6709\u4e25\u91cd\u80be\u53d7\u635f\u60a3\u8005(CLcr <30 mL\/min)\u6216\u80be\u75c5\u7ec8\u672b\u671f\u6ca1\u6709TAGRISSO\u7684\u63a8\u8350\u5242\u91cf[\u89c1\u4e34\u5e8a\u836f\u7406\u5b66(12.3)]\u3002<\/p>\n\n\n\n

8.7 \u809d\u53d7\u635f<\/strong><\/p>\n\n\n\n

\u672a\u8fdb\u884c\u4e13\u95e8\u4e34\u5e8a\u7814\u7a76\u8bc4\u4ef7\u809d\u53d7\u635f\u5bf9osimertinib\u836f\u4ee3\u52a8\u529b\u5b66\u7684\u5f71\u54cd\u3002\u6839\u636e\u7fa4\u4f53\u836f\u4ee3\u52a8\u529b\u5b66(PK) \u5206\u6790\uff0c\u5728\u6709\u8f7b\u5ea6\u809d\u53d7\u635f\u60a3\u8005[\u603b\u80c6\u7ea2\u7d20<\u6b63\u5e38\u7684\u4e0a\u9650(ULN)\u548cAST 1\u81f31.5\u500dULN\u95f4\u6216\u603b\u80c6\u7ea2\u7d201.0\u81f31.5\u500dULN\u95f4\u548c\u4efb\u4f55AST]\u5efa\u8bae\u65e0\u5242\u91cf\u8c03\u6574\u3002\u5bf9\u6709\u4e2d\u5ea6\u6216\u4e25\u91cd\u809d\u53d7\u635f\u60a3\u8005\u5bf9TAGRISSO\u65e0\u63a8\u8350\u5242\u91cf[\u89c1\u4e34\u5e8a\u836f\u7406\u5b66(12.3)]\u3002<\/p>\n\n\n\n

11 \u4e00\u822c\u63cf\u8ff0<\/strong><\/p>\n\n\n\n

Osimertinib\u662f\u4e00\u79cd\u4e3a\u53e3\u670d\u7ed9\u836f\u6fc0\u9176\u6291\u5236\u5242\u3002\u5bf9\u7532\u78fa\u9178osimertinib\u5206\u5b50\u5f0f\u662fC28H33N7O2\u2022CH4O3S\uff0c\u800c\u5206\u5b50\u91cf\u4e3a596 g\/mol\u3002\u5316\u5b66\u540d\u662fN-(2-{2dimethylaminoethyl-methylamino}-4-methoxy-5-{[4-(1-methylindol-3-yl)pyrimidin-2yl]amino}phenyl)prop-2-enamide\u7532\u78fa\u9178\u76d0\u3002Osimertinib\u6709\u4ee5\u4e0b\u7ed3\u6784\u5f0f(\u4e3aosimertinib\u7532\u78fa\u9178\u76d0):<\/p>\n\n\n\n

\u89c1TAGRISSO\u7247\u542b40\u621680 mg osimertinib\uff0c\u5206\u522b\u7b49\u540c\u4e8e47.7\u548c95.4 mg osimertinib\u7532\u78fa\u9178\u76d0\u3002\u5728\u7247\u82af\u4e2d\u65e0\u6d3b\u6027\u6210\u5206\u662f\u7518\u9732\u9187\uff0c\u5fae\u6676\u7ea4\u7ef4\u7d20\uff0c\u4f4e\u53d6\u4ee3\u7f9f\u4e19\u57fa\u7ea4\u7ef4\u7d20\u548c\u786c\u8102\u9170\u5bcc\u9a6c\u9178\u94a0\u3002\u7247\u6d82\u5c42\u7531\u805a\u4e59\u70ef\u9187\uff0c\u4e8c\u6c27\u5316\u949b\uff0c\u805a\u4e59\u4e8c\u91873350\uff0c\u6ed1\u77f3\uff0c\u6c27\u5316\u94c1\u9ec4\uff0c\u6c27\u5316\u94c1\u7ea2\u548c\u6c27\u5316\u94c1\u9ed1\u7ec4\u6210\u3002<\/p>\n\n\n\n

12 \u4e34\u5e8a\u836f\u7406\u5b66<\/strong><\/p>\n\n\n\n

12.1 \u4f5c\u7528\u673a\u5236<\/strong><\/p>\n\n\n\n

\u3000\u3000Osimertinib\u662f\u8868\u76ae\u751f\u957f\u56e0\u5b50\u53d7\u4f53(EGFR)\u7684\u6fc0\u9176\u6291\u5236\u5242\uff0c\u5b83\u53ef\u9006\u5730\u7ed3\u5408\u81f4\u67d0\u4e9b\u7a81\u53d8\u4f53\u5f62\u5f0fEGFR(T790M\uff0cL858R\uff0c\u548c\u5916\u663e\u5b5019\u7f3a\u5931)\u5728\u6d53\u5ea6\u6bd4\u91ce\u751f\u578b\u8f83\u4f4e\u7ea69-\u500d\u3002\u5728\u57f9\u517b\u7ec6\u80de\u4e2d\u548c\u52a8\u7269\u80bf\u7624\u79fb\u690d\u6a21\u578b\uff0cosimertinib\u8868\u73b0\u51fa\u5bf9NSCLC\u7cfb\u7a9d\u85cfEGFR-\u7a81\u53d8(T790M\/L858R\uff0cL858R\uff0cT790M\/\u5916\u663e\u5b5019\u7f3a\u5931\uff0c\u548c\u5916\u663e\u5b5019\u7f3a\u5931)\u548c\uff0c\u81f3\u8f83\u4f4e\u7a0b\u5ea6\uff0c\u91ce\u751f\u578bEGFR\u6269\u589e\u6297\u80bf\u7624\u6d3b\u6027\u3002 \u5728osimertinib\u53e3\u670d\u7ed9\u836f\u540e\u8840\u6d46\u4e2d\u66fe\u88ab\u9274\u5b9a\u4e24\u79cd\u836f\u7406\u5b66\u4e0a-\u6d3b\u6027\u4ee3\u8c22\u7269(AZ7550\u548cAZ5104\u5728\u6bcd\u4f53\u7ea610%\u5faa\u73af)\u4e0eosimertinib\u6709\u76f8\u4f3c\u6291\u5236\u6027\u56fe\u5f62\u3002AZ7550\u663e\u793a\u4e0eosimertinib\u76f8\u4f3c\u6548\u529b\uff0c\u800c AZ5104\u663e\u793a\u5bf9\u5916\u663e\u5b5019\u7f3a\u5931\u548cT790M\u7a81\u53d8\u4f53(\u7ea68-\u500d)\u548c\u91ce\u751f\u578b(\u7ea6 15-\u500d)EGFR\u7684\u6548\u529b\u3002\u5728\u4f53\u5916\uff0cosimertinib\u5728\u4e34\u5e8a\u76f8\u5173\u6d53\u5ea6\u8fd8\u6291\u5236HER2\uff0cHER3\uff0cHER4\uff0cACK1\uff0c\u548cBLK\u7684\u6d3b\u6027\u3002<\/p>\n\n\n\n

12.2 \u836f\u6548\u52a8\u529b\u5b66<\/strong><\/p>\n\n\n\n

\u5fc3\u810f\u7535\u751f\u7406\u5b66<\/strong><\/p>\n\n\n\n

\u5728\u7814\u7a762\u4e2d210\u4f8b\u63a5\u53d7TAGRISSO 80 mg\u6bcf\u5929\u60a3\u8005\u8bc4\u4f30osimertinib\u7684QTc\u95f4\u671f\u5ef6\u957f\u6f5c\u80fd\u3002\u4e00\u9879\u5728\u7a33\u6001\u65f6QTcF\u6570\u636e\u8d8b\u52bf\u4e2d\u592e\u5206\u6790\u663e\u793a\u4ece\u57fa\u7ebf\u6700\u5927\u5747\u6570\u53d8\u5316\u4e3a16.2(\u53cc\u4fa7\u768490%\u53ef\u4fe1\u533a\u95f4(CI)\u7684\u4e0a\u965017.6)msec\u3002\u5728\u7814\u7a762\u4e00\u9879\u5728\u4e00\u4e2a\u5242\u91cfosimertinib 80 mg\u836f\u4ee3\u52a8\u529b\u5b66\/\u836f\u6548\u5b66\u5206\u6790\u63d0\u793a\u4e00\u4e2a\u6d53\u5ea6-\u4f9d\u8d56\u6027QTc\u95f4\u671f\u5ef6\u957f14 msec(\u53cc\u4fa790% CI\u7684\u4e0a\u9650\uff1a16 msec)\u3002<\/p>\n\n\n\n

12.3 \u836f\u4ee3\u52a8\u529b\u5b66<\/strong><\/p>\n\n\n\n

\u8de8\u8d8a 20\u81f3240 mg\u5242\u91cf\u8303\u56f4\u5373\uff0c0.25\u81f33\u500d\u63a8\u8350\u5242\u91cf)\u5728\u53e3\u670d\u7ed9\u836f\u540eOsimertinib\u7684\u8840\u6d46\u6d53\u5ea6-\u65f6\u95f4\u66f2\u7ebf\u4e0b\u9762\u79ef(AUC)\u548c\u8840\u6d46\u5cf0\u6d53\u5ea6(Cmax)\u5448\u5242\u91cf\u6b63\u6bd4\u4f8b\u589e\u52a0\u548c\u8868\u73b0\u7ebf\u6027\u836f\u4ee3\u52a8\u529b\u5b66(PK)\u3002<\/p>\n\n\n\n

TAGRISSO\u53e3\u670d\u6bcf\u59291\u6b21\u7ed9\u836f\u5bfc\u81f4\u7ea63-\u500d\u79ef\u84c4\u4e0e\u5728\u7ed9\u836f\u540e15\u5929\u5b9e\u73b0\u7a33\u6001\u66b4\u9732\u3002\u5728\u7a33\u6001\u65f6\uff0cCmax \u4e0eCmin(\u6700\u4f4e\u6d53\u5ea6)\u6bd4\u503c\u4e3a1.6-\u500d\u3002<\/p>\n\n\n\n

\u5438\u6536<\/strong><\/p>\n\n\n\n

Osimertinib\u81f3Cmax\u8fbe\u5cf0\u4e2d\u4f4d\u65f6\u95f4\u4e3a6\u5c0f\u65f6(\u8303\u56f43-24\u5c0f\u65f6)\/<\/p>\n\n\n\n

\u4e00\u4e2a20 mg TAGRISSO\u7247\u4e0e\u4e00\u4e2a\u9ad8-\u8102\u80aa\uff0c\u9ad8-\u70ed\u91cf\u9910(\u542b\u7ea658\u514b\u8102\u80aa\u548c1000\u5361\u8def\u91cc)\u7ed9\u836f\u540e\uff0cosimertinib\u7684Cmax\u548cAUC\u4e0e\u7a7a\u8179\u6761\u4ef6\u6bd4\u8f83\u5206\u522b\u589e\u52a014%\u548c19%\u3002<\/p>\n\n\n\n

\u5206\u5e03<\/strong><\/p>\n\n\n\n

Osimertinib\u7a33\u6001\u65f6\u5747\u6570\u5206\u5e03\u5bb9\u79ef(Vss\/F)\u4e3a986 L\u3002Osimertinib\u7684\u8840\u6d46\u86cb\u767d\u7ed3\u5408\u662f\u53ef\u80fd\u9ad8\u5ea6\u6839\u636e\u5176\u7269\u7406\u5316\u5b66\u6027\u8d28\u3002<\/p>\n\n\n\n

\u6d88\u9664<\/strong><\/p>\n\n\n\n

Osimertinib\u8840\u6d46\u6d53\u5ea6\u968f\u65f6\u95f4\u51cf\u4f4e\u548cosimertinib\u534a\u8870\u671f\u7684\u7fa4\u4f53\u4f30\u7b97\u5747\u6570\u534a\u8870\u671f\u4e3a48\u5c0f\u65f6\uff0c\u800c\u53e3\u670d\u6e05\u9664\u7387(CL\/F)\u4e3a14.2(L\/h)\u3002<\/p>\n\n\n\n

\u4ee3\u8c22<\/strong><\/p>\n\n\n\n

\u5728\u4f53\u5916Osimertinib\u7684\u4e3b\u8981\u4ee3\u8c22\u9014\u5f84\u662f\u6c27\u5316(\u5360\u4f18\u52bfCYP3A)\u548c\u53bb\u70f7\u57fa\u5316\u3002\u53e3\u670d\u7ed9\u4e88TAGRISSO\u540e\u66fd\u9274\u5b9a\u4e24\u4e2a\u836f\u7406\u5b66\u4e0a\u6d3b\u6027\u4ee3\u8c22\u7269(AZ7550\u548cAZ5104)\u3002\u5728\u7a33\u6001\u65f6\u5404\u4ee3\u8c22\u7269(AZ5104\u548cAZ7550)\u7684\u51e0\u4f55\u5747\u6570\u66b4\u9732(AUC)\u4e3aosimertinib\u7684\u66b4\u9732\u7ea610%\u3002<\/p>\n\n\n\n

\u6392\u6cc4<\/strong><\/p>\n\n\n\n

Osimertinib\u662f\u4e3b\u8981\u5730\u5728\u7caa\u4e2d\u88ab\u6d88\u9664(68%)\u548c\u5728\u5c3f\u4e2d\u8f83\u4f4e\u7a0b\u5ea6(14%)\u3002\u672a\u53d8\u5316osimertinib\u5360\u6d88\u9664\u7684\u7ea62%\u3002<\/p>\n\n\n\n

\u7279\u6b8a\u4eba\u7fa4<\/strong><\/p>\n\n\n\n

\u6839\u636e\u5e74\u9f84\u3002\u6027\u522b\uff0c\u6c11\u65cf\uff0c\u4f53\u91cd\uff0c\u5438\u70df\u72b6\u6001\uff0c\u8f7b\u5ea6(CLcr 60-89 mL\/min)\u6216\u4e2d\u5ea6(CLcr 30-59 mL\/min)\u80be\u53d7\u635f\uff0c\u6216\u8f7b\u5ea6\u809d\u53d7\u635f(\u603b\u80c6\u7ea2\u7d20<\/p>\n\n\n\n

\u836f\u7269\u76f8\u4e92\u4f5c\u7528<\/strong><\/p>\n\n\n\n

\u5176\u4ed6\u836f\u7269\u5bf9TAGRISSO\u7684\u5f71\u54cd\uff1a<\/p>\n\n\n\n

\u5f3aCYP3A\u6291\u5236\u5242\uff1a\u672a\u8fdb\u884c\u5f3aCYP3A\u6291\u5236\u5242\u5b58\u5728TAGRISSO\u4e34\u5e8a\u7814\u7a76\u8bc4\u4ef7[\u89c1\u836f\u7269\u76f8\u4e92\u4f5c\u7528(7.1)]\u3002<\/p>\n\n\n\n

\u5f3aCYP3A\u8bf1\u5bfc\u5242\uff1a\u672a\u8fdb\u884c\u5b58\u5728\u5f3aCYP3A\u8bf1\u5bfc\u5242\u4e34\u5e8a\u7814\u7a76\u8bc4\u4ef7TAGRISSO[\u89c1\u836f\u7269\u76f8\u4e92\u4f5c\u7528(7.1)]\u3002<\/p>\n\n\n\n

\u80c3\u9178\u51cf\u4f4e\u836f\u7269\uff1a\u5355\u6b2180 mg TAGRISSO\u7247\u540e40 mg\u5965\u7f8e\u62c9\u5511[omeprazole]\u7ed9\u836f\u51715\u5929\u540c\u65f6\u7ed9\u836f\uff0c\u5bf9osimertinib\u7684\u66b4\u9732\u6ca1\u6709\u5f71\u54cd\u3002<\/p>\n\n\n\n

Osimertinib\u5bf9\u5176\u4ed6\u836f\u7269\u7684\u5f71\u54cd\uff1a<\/strong><\/p>\n\n\n\n

CYP450\u4ee3\u8c22\u9014\u5f84\uff1aOsimertinib\u5728\u4f53\u5916\u662f\u4e00\u4e2aCYP3A\u7ade\u4e89\u6027\u6291\u5236\u5242\uff0c\u4f46\u4e0d\u662fCYP2C8\uff0c1A2\uff0c2A6\uff0c2B6\uff0c2C9\uff0c2C19\uff0c2D6\u548c2E1\u3002Osimertinib\u8bf1\u5bfcCYP3A4(\u5b55\u73af\u70f7X\u4f9d\u8d56)\u548cCYP1A2\u9176\u3002<\/p>\n\n\n\n

\u8f6c\u8fd0\u86cb\u767d\u7cfb\u7edf\uff1a\u6839\u636e\u4f53\u5916\u7814\u7a76\uff0cosimertinib\u662f\u4e00\u4e2aP-\u7cd6\u86cb\u767d\u5e95\u7269\u548cBCRP\u548c\u4e0d\u662fOATP1B1\u548cOATP1B3\u7684\u5e95\u7269\u3002\u5728\u4f53\u5916Osimertinib\u662fBCRP\u7684\u4e00\u4e2a\u6291\u5236\u5242\u548c\u4e0d\u6291\u5236P-\u7cd6\u86cb\u767d\uff0cOAT1\uff0cOAT3\uff0cOATP1B1\uff0cOATP1B3\uff0cMATE1\uff0cMATE2K\u548cOCT2\u3002<\/p>\n\n\n\n

13 \u975e\u4e34\u5e8a\u6bd2\u7406\u5b66<\/strong><\/p>\n\n\n\n

13.1 \u764c\u53d1\u751f\uff0c\u7a81\u53d8\u53d1\u751f\uff0c\u751f\u80b2\u529b\u53d7\u635f<\/strong><\/p>\n\n\n\n

\u672a\u66fd\u7528osimertinib\u8fdb\u884c\u81f4\u764c\u6027\u7814\u7a76\u3002\u5728\u4f53\u5916\u548c\u4f53\u5185\u8bd5\u9a8cOsimertinib\u4e0d\u81f4\u9057\u4f20\u635f\u4f24\u3002<\/p>\n\n\n\n

\u6839\u636e\u52a8\u7269\u4e2d\u7814\u7a76\uff0c\u7528TAGRISSO\u6cbb\u7597\u53ef\u80fd\u635f\u4f24\u96c4\u6027\u751f\u80b2\u529b\u3002\u5728\u5927\u9f20\u548c\u72ac\u66b4\u9732\u4e8eosimertinib \u51711\u4e2a\u6708\u6216\u66f4\u591a\u5728\u777e\u4e38\u5b58\u5728\u9000\u884c\u6027\u53d8\u5316\uff0c\u5728\u5927\u9f20\u4e2d\u6709\u53ef\u9006\u6027\u8bc1\u636e\u3002\u5bf9\u5927\u9f20\u7ed9\u4e88osimertinib\u5171\u7ea610\u5468\u540e\u5728\u5242\u91cf40 mg\/kg\uff0c\u5728\u66b4\u9732\u5728\u60a3\u8005\u7684\u63a8\u8350\u5242\u91cf80 mg\u89c2\u5bdf\u5230AUC\u66b4\u9732\u76840.5-\u500d\u65f6\uff0c\u6709\u96c4\u6027\u751f\u80b2\u529b\u51cf\u4f4e\u663e\u793a\u4e3a\u4e0e\u88ab\u6cbb\u7597\u96c4\u6027\u5728\u4ea4\u914d\u7684\u672a\u6cbb\u7597\u96cc\u6027\u4e2d\u690d\u5165\u524d\u4e22\u5931\u589e\u52a0\u3002<\/p>\n\n\n\n

\u672a\u66fd\u8fdb\u884c\u975e\u4e34\u5e8a\u96cc\u6027\u751f\u80b2\u529b\u7814\u7a76\u3002\u5728\u91cd\u590d\u5242\u91cf\u6bd2\u6027\u7814\u7a76\u4e2d\uff0c\u5728\u5927\u9f20\u66b4\u9732\u4e8eosimertinib\u51711\u4e2a\u6708\u6216\u66f4\u591a\uff0c\u60a3\u8005\u63a8\u8350\u5242\u91cf80 mg\u89c2\u5bdf\u5230AUC\u66b4\u9732\u76840.3-\u500d\u65f6\u89c1\u5230\u5728\u5375\u5de2\u4e2d\u52a8\u60c5\u95f4\u671f\uff0c\u9ec4\u4f53\u9000\u884c\u6027\u53d8\u6027\u548c\u5728\u5b50\u5bab\u548c\u9634\u9053\u4e0a\u76ae\u53d8\u8584\u7684\u7ec4\u7ec7\u5b66\u8bc1\u636e\u3002\u7ed9\u836f\u540e1\u4e2a\u6708\u5375\u5de2\u4e2d\u89c1\u5230\u7684\u53d1\u73b0\u8868\u73b0\u51fa\u53ef\u9006\u6027\u7684\u8bc1\u636e\u3002<\/p>\n\n\n\n

14 \u4e34\u5e8a\u7814\u7a76<\/strong><\/p>\n\n\n\n

\u5728\u4e24\u9879\u591a\u4e2d\u5fc3\uff0c\u5355\u81c2\uff0c\u5f00\u653e\u4e34\u5e8a\u8bd5\u9a8c\uff0c\u7814\u7a761\u548c\u7814\u7a762\uff0c\u5728\u6709\u8f6c\u79fbEGFR T790M\u7a81\u53d8-\u9633\u6027NSCLC\u60a3\u8005\u5bf9\u4ee5\u524d\u5168\u8eab\u6cbb\u7597\u5df2\u8fdb\u5c55\uff0c\u5305\u62ec\u4e00\u79cdEGFR TKI\u8bc1\u5b9eTAGRISSO\u7684\u7597\u6548\u3002\u6240\u6709\u60a3\u8005\u90fd\u88ab\u8981\u6c42\u88abcobas\u00ae EGFR \u7a81\u53d8\u6d4b\u8bd5\u68c0\u51faEGFR T790M\u7a81\u53d8-\u9633\u6027NSCLC\u548c\u63a5\u53d7TAGRISSO 80 mg\u6bcf\u59291\u6b21\u3002\u4e24\u9879\u8bd5\u9a8c\u4e3b\u8981\u7597\u6548\u7ed3\u5c40\u6d4b\u91cf\u662f\u7531\u76f2\u6001\u72ec\u7acb\u4e2d\u592e\u8bc4\u5ba1(BICR) \u6309\u7167RECIST v1.1\u8bc4\u4ef7\u7684\u5ba2\u89c2\u53cd\u5e94\u7387(ORR)\uff0c\u53cd\u5e94\u65f6\u95f4(DOR)\u662f\u4e00\u9644\u52a0\u7ed3\u5c40\u6d4b\u91cf\u3002<\/p>\n\n\n\n

\u7814\u7a761\u4eba\u7fa4\u7279\u5f81\u662f\uff1a\u4e2d\u4f4d\u5e74\u9f8462\u5c81(\u8303\u56f437\u81f389)\uff0c\u5973\u6027(66%)\uff0c\u767d\u79cd\u4eba(38%)\uff0c\u4e9a\u88d4(58%)\uff0c\u6c38\u672a\u5438\u70df\u8005(67%)\uff0c\u4e16\u754c\u536b\u751f\u7ec4\u7ec7(WHO)\u6027\u80fd\u72b6\u60010(34%)\u62161(66%)\uff0c\u817a\u764c\u7ec4\u7ec7\u5b66(97%)\uff0c1\u4ee5\u524d\u7ebf\u6cbb\u7597[\u4ec5EGFR-TKI\u6cbb\u7597\uff0c\u4e8c\u7ebf\uff0c\u5316\u7597\u672a\u6cbb\u7597\u8fc7](30%)\uff0c2\u6216\u66f4\u591a\u4ee5\u524d\u7ebf\u6cbb\u7597(70%)\u3002\u80f8\u5916\u90e8\u4f4d\u8f6c\u79fb\u5305\u62ec\u809d(32%)\uff0c\u9aa8(51%)\uff0c\u548c\u8111(37%)\u3002\u4f53\u7ec6\u80deEGFR\u7a81\u53d8\u9664\u4e86T790M\u662f\u5916\u663e\u5b5019\u7f3a\u5931(71%)\uff0cL858R(25%)\uff0cG719X(2%)\uff0c\u548cS768I(2%)\u3002<\/p>\n\n\n\n

\u7814\u7a762\u4eba\u7fa4\u7279\u5f81\u662f\u4e2d\u4f4d\u5e74\u9f8464\u5c81(\u8303\u56f435\u81f388)\uff0c\u5973\u6027(70%)\uff0c\u767d\u79cd\u4eba(34%)\uff0c\u4e9a\u88d4(63%)\uff0c\u6c38\u672a\u5438\u70df\u8005(76%)\uff0c\u4e16\u754c\u8bf6\u536b\u751f\u7ec4\u7ec7(WHO)\u6027\u80fd\u72b6\u60010(40%)\u62161(60%)\uff0c\u817a\u764c\u7ec4\u7ec7\u5b66(95%)\uff0c\u53ea\u67091\u6b21\u4ee5\u524d\u7ebf\u6cbb\u7597[EGFR-TKI \u6cbb\u7597\uff0c\u4e8c\u7ebf\uff0c\u5316\u7597\u672a\u6cbb\u7597\u8fc7](32%)\uff0c2\u6216\u66f4\u591a\u4ee5\u524d \u7ebf\u6cbb\u7597(68%)\u3002\u80f8\u90e8\u5916\u90e8\u4f4d\u8f6c\u79fb\u5305\u62ec\u809d(26%)\uff0c\u9aa8(43%)\uff0c\u548c\u8111(41%)\u3002\u4f53\u7ec6\u80deEGFR\u7a81\u53d8\u9664\u4e86T790M\u662f\u5916\u663e\u5b5019\u7f3a\u5931(65%)\uff0cL858R(32%)\uff0cG719X(2%)\uff0c\u548cS768I(1%)\u3002<\/p>\n\n\n\n

\u88684\u603b\u7ed3\u6765\u81ea\u7814\u7a761\u548c\u7814\u7a762\u88abBICR\u7684\u7597\u6548\u7ed3\u679c\u3002\u60a3\u8005\u7684\u591a\u6570(96%)\u6709\u88ab\u786e\u8bc1\u7684\u5ba2\u89c2\u53cd\u5e94\u7387\u5df2\u8fdb\u884c\u53cd\u5e94\u8303\u56f4\u4ece1.1\u81f35.6\u4e2a\u6708\u5bf9\u7814\u7a761\u4e2d\u4f4d\u968f\u8bbf\u65f6\u95f44.2\u4e2a\u6708\u548c\u5bf9\u7814\u7a762\u4e3a4.0\u4e2a\u6708\u3002<\/p>\n\n\n\n

\u5728\u7814\u7a761\u5206\u5f00\u7684\u5242\u91cf\u53d1\u73b0\u90e8\u5206\uff0c63\u4f8b\u6709\u4e2d\u592e\u786e\u8bc1T790M\u9633\u6027\u7684\u60a3\u8005NSCLC\u7528\u4ee5\u524d\u5168\u8eab\u6cbb\u7597\u8fdb\u5c55\uff0c\u5305\u62ec\u88ab\u7ed9\u4e88\u4e00\u79cdEGFR TKI TAGRISSO 80 mg\u3002\u5728\u8fd9\u4e9b\u60a3\u8005\u4e2d\uff0cBICR-\u786e\u8bc1\u5ba2\u89c2\u53cd\u5e94\u7387\u4e3a51%(32\/63)\u548c\u4ece\u9996\u6b21\u8bb0\u5f55\u53cd\u5e94\u7684\u4e2d\u4f4d\u53cd\u5e94\u65f6\u95f4\u4e3a12.4\u4e2a\u6708\u3002<\/p>\n\n\n\n

16 \u5982\u4f55\u4f9b\u5e94\/\u8d2e\u5b58\u548c\u5904\u7f6e<\/strong><\/p>\n\n\n\n

80 mg \u7247\uff1a<\/strong>\u7c73\u8272\uff0c\u692d\u5706\u5f62\u548c\u53cc\u51f8\u7247\u5728\u4e00\u4fa7\u6807\u8bb0\u6709\u201cAZ 80\u201d\u548c\u53cd\u9762\u5e73\u5766\u548c\u53ef\u5f97\u523030\u7247\u74f6(NDC 0310-1350-30)\u3002<\/p>\n\n\n\n

40 mg \u7247\uff1a<\/strong>\u7c73\u8272\uff0c\u5706\u548c\u53cc\u51f8\u7247\u5728\u4e00\u4fa7\u6807\u8bb0\u6709\u201cAZ 40\u201d\u548c\u53cd\u9762\u5e73\u5766\u548c\u53ef\u5f97\u523020\u7247\u74f6(NDC 0310-1349-30)\u3002<\/p>\n\n\n\n

\u8d2e\u5b58TAGRISSO\u74f6\u572825\u00b0C(77\u00b0F)\u3002\u5916\u51fa\u5141\u8bb8\u81f315-30\u00b0C(59-86\u00b0F)[\u89c1USP\u63a7\u5236\u5ba4\u6e29]\u3002<\/p>\n\n\n\n

17 \u60a3\u8005\u54a8\u8be2\u8d44\u6599<\/strong><\/p>\n\n\n\n

\u5fe0\u544a\u60a3\u8005\u9605\u8bfbFDA-\u6279\u51c6\u7684\u60a3\u8005\u8bf4\u660e\u4e66(\u60a3\u8005\u8d44\u6599)\u3002<\/p>\n\n\n\n

\u95f4\u8d28\u6027\u80ba\u75be\u75c5\/\u80ba\u708e<\/strong><\/p>\n\n\n\n

\u544a\u77e5\u60a3\u8005\u4e25\u91cd\u6216\u81f4\u547d\u6027ILD\uff0c\u5305\u62ec\u80ba\u708e\u7684\u98ce\u9669\u3002\u5fe0\u544a\u60a3\u8005\u7acb\u5373\u8054\u7cfb\u4ed6\u4eec\u7684\u536b\u751f\u4fdd\u5065\u63d0\u4f9b\u8005\u62a5\u544a\u65b0\u6216\u6076\u5316\u7684\u547c\u5438\u75c7\u72b6[\u89c1\u8b66\u544a\u548c\u6ce8\u610f\u4e8b\u9879(5.1)]\u3002<\/p>\n\n\n\n

QTc\u95f4\u671f\u5ef6\u957f<\/strong><\/p>\n\n\n\n

\u544a\u77e5\u60a3\u8005\u53ef\u80fd\u662f\u663e\u8457QTc\u5ef6\u957f\u7684\u6307\u793a\u6027\u75c7\u72b6\u5305\u62ec\u7729\u6655\uff0c\u5934\u8f7b\u811a\u91cd\uff0c\u548c\u6655\u53a5\u3002\u5fe0\u544a\u60a3\u8005\u62a5\u544a\u8fd9\u4e9b \u75c7\u72b6\u548c\u544a\u77e5\u5176\u533b\u751f\u6709\u5173\u4f7f\u7528\u4efb\u4f55\u5fc3\u6216\u8840\u538b\u836f\u7269[\u89c1\u8b66\u544a\u548c\u6ce8\u610f\u4e8b\u9879(5.2)].<\/p>\n\n\n\n

\u5fc3\u808c\u75c5\u53d8<\/strong><\/p>\n\n\n\n

TAGRISSO\u53ef\u80fd\u81f4\u5fc3\u808c\u75c5\u53d8\u3002\u5fe0\u544a\u60a3\u8005\u7acb\u5373\u62a5\u544a\u4efb\u4f55\u5fc3\u8870\u4efb\u4f55\u4f53\u5f81\u6216\u75c7\u72b6\u81f3\u4ed6\u4eec\u7684\u536b\u751f\u4fdd\u5065\u63d0\u4f9b\u8005[\u89c1\u8b66\u544a\u548c\u6ce8\u610f\u4e8b\u9879(5.3)].<\/p>\n\n\n\n

\u80da\u80ce-\u80ce\u513f\u6bd2\u6027<\/strong><\/p>\n\n\n\n