{"id":4898,"date":"2023-06-18T23:46:11","date_gmt":"2023-06-18T15:46:11","guid":{"rendered":"http:\/\/dh.oncolab.cn\/index.php\/2023\/06\/18\/%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e5%ad%a6-%e7%ac%ac21%e7%ab%a0%ef%bc%9apd-1%e9%98%bb%e6%96%ad%e5%9c%a8%e8%82%be%e7%bb%86%e8%83%9e%e7%99%8c%e4%b8%ad%e7%9a%84%e4%bd%9c%e7%94%a8%ef%bc%88%e4%b8%8a\/"},"modified":"2023-06-18T23:46:11","modified_gmt":"2023-06-18T15:46:11","slug":"%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e5%ad%a6-%e7%ac%ac21%e7%ab%a0%ef%bc%9apd-1%e9%98%bb%e6%96%ad%e5%9c%a8%e8%82%be%e7%bb%86%e8%83%9e%e7%99%8c%e4%b8%ad%e7%9a%84%e4%bd%9c%e7%94%a8%ef%bc%88%e4%b8%8a","status":"publish","type":"post","link":"http:\/\/dh.oncolab.cn\/index.php\/2023\/06\/18\/%e8%82%bf%e7%98%a4%e5%85%8d%e7%96%ab%e5%ad%a6-%e7%ac%ac21%e7%ab%a0%ef%bc%9apd-1%e9%98%bb%e6%96%ad%e5%9c%a8%e8%82%be%e7%bb%86%e8%83%9e%e7%99%8c%e4%b8%ad%e7%9a%84%e4%bd%9c%e7%94%a8%ef%bc%88%e4%b8%8a\/","title":{"rendered":"\u80bf\u7624\u514d\u75ab\u5b66-\u7b2c21\u7ae0\uff1aPD-1\u963b\u65ad\u5728\u80be\u7ec6\u80de\u764c\u4e2d\u7684\u4f5c\u7528\uff08\u4e0a\uff09"},"content":{"rendered":"
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<\/p>\n<\/section>\n<\/section>\n

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21.1 \u7b80\u4ecb<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u80be\u7ec6\u80de\u764c ( RCC) \u662f\u6700\u5e38\u89c1\u7684\u80be\u764c\u7c7b\u578b\uff0c\u5728\u7f8e\u56fd\u662f\u7b2c\u516b\u5927\u5e38\u89c1\u764c\u75c7\uff0c\u53d1\u75c5\u9ad8\u5cf0\u5728 60 – 70 \u5c81\u4e4b\u95f4\uff0c\u7537\u6027\u5c45\u591a\u3002\u8f6c\u79fb\u6027\u80be\u7ec6\u80de\u764c (mRCC) \u4e3b\u8981\u5bf9\u7ec6\u80de\u6bd2\u5316\u7597\u8010\u836f\uff0c\u4e5f\u5bf9\u653e\u7597\u8010\u836f\u3002<\/p>\n

\u57fa\u4e8e\u51e0\u4e2a\u6709\u8da3\u7684\u89c2\u5bdf\u7ed3\u679c\uff0cRCC \u88ab\u8ba4\u4e3a\u662f\u4e00\u79cd\u514d\u75ab\u53cd\u5e94\u6027\u80bf\u7624\u3002\u9996\u5148\uff0c\u5728\u4e00\u4e9b\u60a3\u8005\u4e2d\u53d1\u73b0\u8f6c\u79fb\u6027\u80ba\u75c5\u7076\u53ef\u81ea\u53d1\u6d88\u9000\u3002\u5176\u6b21\uff0c\u5728 RCC \u4e2d\uff0c\u4f7f\u7528\u5e72\u6270\u7d20\u03b1 (IFN-5\u03b1) \u548c\u767d\u7ec6\u80de\u4ecb\u7d20 2 (IL-2) \u7b49\u514d\u75ab\u523a\u6fc0\u6027\u7ec6\u80de\u56e0\u5b50\u7684\u514d\u75ab\u7597\u6cd5\u4e5f\u6709\u4e00\u5b9a\u7684\u7597\u6548\uff0c\u5e76\u4e14\u51e0\u5341\u5e74\u6765\u8be5\u514d\u75ab\u7597\u6cd5\u4e00\u76f4\u662f mRCC \u7684\u6807\u51c6\u6cbb\u7597\u65b9\u6cd5\u3002<\/p>\n

\u5c3d\u7ba1 IL-2 \u53ef\u7528\u4e8e\u4f4e\u5242\u91cf\u548c\u9ad8\u5242\u91cf\u65b9\u6848\uff0c\u4f46\u7f8e\u56fd\u98df\u54c1\u548c\u836f\u54c1\u7ba1\u7406\u5c40 (FDA) \u5728 1992 \u5e74\u4ec5\u6279\u51c6\u4e86\u9ad8\u5242\u91cf\u65b9\u6848\u3002\u4e00\u9879\u56de\u987e\u6027\u5206\u6790\u8868\u660e\uff1a\u5728 259 \u540d\u63a5\u53d7\u9ad8\u5242\u91cf IL-2 \u6cbb\u7597\u7684 mRCC \u60a3\u8005\u540e\uff0c1986 \u5e74\u81f3 2006 \u5e74\u95f4\u62a5\u544a\u7684\u603b\u4f53\u53cd\u5e94\u7387 (ORR) \u4e3a 20%\uff089% \u5b8c\u5168\u53cd\u5e94 (CR) \u548c 11% \u90e8\u5206\u53cd\u5e94 (PR)\uff09\u3002<\/p>\n

mRCC\u514d\u75ab\u6cbb\u7597\u5177\u6709\u5f88\u5927\u5438\u5f15\u529b\u7684\u539f\u56e0\u4e4b\u4e00\u662fIL-2 \u7597\u6cd5\u5177\u6709\u9ad8 CR \u7387\u3002\u4f46\u7531\u4e8e\u5176\u975e\u7279\u5f02\u6027\u6297\u80bf\u7624\u6d3b\u6027\uff0cIL-2 \u7ed9\u836f\u7684\u5242\u91cf\u4e0e\u836f\u7269\u7684\u6bd2\u6027\u76f8\u5173\uff0c\u53ef\u5f15\u8d77\u5168\u8eab\u708e\u75c7\u53cd\u5e94\u7efc\u5408\u5f81\u548c\u809d\u80be\u6bd2\u6027\u3002\u7531\u4e8e\u8fd9\u4e9b\u6bd2\u526f\u4f5c\u7528\uff0c\u5982\u4eca IL-2 \u7597\u6cd5\u7684\u7528\u9014\u4ec5\u9650\u4e8e\u5e74\u8f7b\u548c\u5065\u5eb7\u7684\u5408\u5e76\u75c7\u6700\u5c11\u7684\u60a3\u8005\u3002<\/p>\n

\u665a\u671f RCC \u7684\u6807\u51c6\u836f\u7269\u6cbb\u7597\u5305\u62ec\u8840\u7ba1\u5185\u76ae\u751f\u957f\u56e0\u5b50 (VEGF) \u53d7\u4f53\u3001\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242 (TKI) \u548c\u54fa\u4e73\u52a8\u7269\u96f7\u5e15\u9709\u7d20\u9776\u86cb\u767d (mTOR) \u6291\u5236\u5242\u3002\u7136\u800c\uff0c\u5c3d\u7ba1\u8fd9\u4e9bmRCC \u9776\u5411\u7597\u6cd5\u7684\u6279\u51c6\u5728\u6539\u5584\u4e34\u5e8a\u7ed3\u679c\u65b9\u9762\u53d6\u5f97\u4e86\u6210\u529f\uff0c\u4f46\u65b0\u8bca\u65ad mRCC \u60a3\u8005\u7684\u4e2d\u4f4d\u603b\u751f\u5b58\u671f (OS) \u4ec5\u4e3a 22-29 \u4e2a\u6708\uff0c\u8fd9\u51f8\u663e\u4e86\u8be5\u60a3\u8005\u7fa4\u4f53\u9700\u8981\u989d\u5916\u6cbb\u7597\u7684\u5fc5\u8981\u6027\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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21.2 PD-1\u53ca\u5176\u914d\u4f53\u5728RCC\u4e2d\u7684\u4f5c\u7528<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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RCC \u901a\u5e38\u8868\u73b0\u51fa\u663e\u8457\u7684\u514d\u75ab\u7ec6\u80de\u6d78\u6da6\uff0c\u7531\u591a\u79cd\u7ec6\u80de\u7c7b\u578b\u7ec4\u6210\uff1aT \u7ec6\u80de\u3001\u81ea\u7136\u6740\u4f24 (NK) \u7ec6\u80de\u3001\u6811\u7a81\u72b6\u7ec6\u80de (DC) \u548c\u5de8\u566c\u7ec6\u80de\u3002\u5c3d\u7ba1\u6709\u5f3a\u70c8\u7684\u6dcb\u5df4\u7ec6\u80de\u6d78\u6da6\uff0c\u4f46\u514d\u75ab\u529f\u80fd\u969c\u788d\u4f1a\u4fc3\u8fdb RCC \u80bf\u7624\u7684\u751f\u957f\u548c\u9003\u9038\u3002\u6297\u80bf\u7624\u53cd\u5e94\u53d7\u635f\u7684\u90e8\u5206\u539f\u56e0\u662f\u80bf\u7624\u8bf1\u5bfc\u7684 DC \u5206\u5316\u5f02\u5e38\uff0c \u76f8\u5173\u57fa\u56e0\u8bf1\u5bfc\u7684T \u7ec6\u80de\u8017\u7aed\u3002<\/p>\n

\u8d8a\u6765\u8d8a\u591a\u7684\u8bc1\u636e\u8868\u660e\uff0c\u65b0\u578b\u514d\u75ab\u8c03\u8282\u7597\u6cd5\u53ef\u660e\u663e\u589e\u5f3a\u6297\u80bf\u7624\u514d\u75ab\u529b\u3002\u901a\u5e38\uff0c\u6d3b\u5316\u7684 T \u7ec6\u80de\u3001B \u7ec6\u80de\u3001NK \u7ec6\u80de\u3001DC \u548c\u5355\u6838\u7ec6\u80de\u8868\u8fbe PD-1 \u4ee5\u9650\u5236\u708e\u75c7\u72b6\u6001\uff08\u5982\u611f\u67d3\uff09\u671f\u95f4\u7684\u81ea\u8eab\u514d\u75ab\u3002\u8bb8\u591a\u80bf\u7624\u8868\u8fbe PD-L1 \uff0c\u4ee5\u4e0b\u8c03 T \u7ec6\u80de\u53cd\u5e94\u3002<\/p>\n

\u51e0\u9879\u7814\u7a76\u8c03\u67e5\u4e86 PD-1 \u548c PD-L1 \u8868\u8fbe\u5728 RCC \u4e2d\u7684\u751f\u7269\u5b66\u548c\u9884\u540e\u4f5c\u7528\u3002\u7814\u7a76\u8bc1\u5b9e\uff0cPD-L1\u5728\u539f\u53d1\u6027\u548c\u8f6c\u79fb\u6027 RCC \u6807\u672c\u4e2d\u8868\u8fbe\u663e\u8457\u4e0a\u8c03\uff0c\u4f46\u5728\u6b63\u5e38\u80be\u7ec4\u7ec7\u4e2d\u4e0d\u8868\u8fbe \u3002Thompson \u53ca\u5176\u540c\u4e8b\u5728196\u4e2a\u80be\u5207\u9664\u6807\u672c\u4e2d\u8bc4\u4f30\u4e86PD-1\u548cPD-L1\u7684\u514d\u75ab\u7ec4\u7ec7\u5316\u5b66 (IHC) \u8868\u8fbe\u60c5\u51b5\u3002PD-1 \u5728 56% \u7684\u5305\u542b\u5355\u6838\u7ec6\u80de\u6d78\u6da6\u7684\u60a3\u8005\u80bf\u7624\u4e2d\u8868\u8fbe\uff0c\u800c\u4e0d\u5728 RCC \u80bf\u7624\u7ec6\u80de\u4e2d\u8868\u8fbe\u3002\u6b64\u5916\uff0cPD-L1 \u8868\u8fbe\u4e0e\u4fb5\u88ad\u6027\u80bf\u7624\u7279\u5f81\u76f8\u5173\uff0c\u4f8b\u5982\u8f83\u9ad8\u7684\u80bf\u7624\u6dcb\u5df4\u7ed3\u8f6c\u79fb (TNM) \u9636\u6bb5\u3001\u574f\u6b7b\u6216\u8089\u7624\u6837\u5206\u5316\u7684\u5b58\u5728\u4ee5\u53ca\u764c\u75c7\u7279\u5f02\u6027\u6b7b\u4ea1\u7387\u7684\u98ce\u9669\u589e\u52a0\u3002\u6b64\u5916\uff0cFrigola \u7b49\u4eba\u901a\u8fc7 ELISA \u5728\u4e00\u7cfb\u5217 172 \u540d RCC \u60a3\u8005\u4e2d\u91cf\u5316\u53ef\u6eb6\u6027 PD-L1\u3002\u663e\u793a\u8f83\u9ad8\u6c34\u5e73\u7684 PD-L1\u3001\u4fb5\u88ad\u6027\u75c5\u7406\u7279\u5f81\u548c\u6b7b\u4ea1\u98ce\u9669\u589e\u52a0\u4e4b\u95f4\u5b58\u5728\u663e\u7740\u5173\u8054\u3002<\/p>\n

PD-1\u548cPD-L1 \u90fd\u5728CD4 + <\/sup>CD25 + <\/sup>\u8c03\u8282\u6027 T \u7ec6\u80de (Tregs) \u4e0a\u8868\u8fbe\uff0c\u4f46\u5b83\u4eec\u662f\u5426\u5f71\u54cdTregs\u7684\u529f\u80fd\u5c1a\u4e0d\u5b8c\u5168\u6e05\u695a\u3002Tregs \u6d78\u6da6\u7406\u8bba\u4e0a\u53ef\u4fc3\u8fdb RCC \u7684\u4fc3\u8840\u7ba1\u751f\u6210\u8868\u578b\uff0c\u5e76\u4e0e RCC \u7684\u5206\u671f\u548c\u7b49\u7ea7\u76f8\u5173\u3002\u6709\u8da3\u7684\u662f\uff0c\u8212\u5c3c\u66ff\u5c3c\u548c\u7d22\u62c9\u975e\u5c3c\u6cbb\u7597\u90fd\u964d\u4f4e\u4e86\u80bf\u7624\u6d78\u6da6\u6027 Treg \u7684\u767e\u5206\u6bd4\uff0c\u800c\u4f9d\u7ef4\u83ab\u53f8\uff08\u4e00\u79cd\u514d\u75ab\u6291\u5236\u5242\u548c\u916a\u6c28\u9178\u6fc0\u9176\u6291\u5236\u5242\uff09\u6539\u5584\u4e86\u80bf\u7624\u6d78\u6da6\u6027 Treg \u7684\u767e\u5206\u6bd4\u3002\u6b63\u5982\u5728\u5176\u4ed6\u80bf\u7624\u7ec4\u7ec7\u5b66\u4e2d\u6240\u89c2\u5bdf\u5230\u7684\u90a3\u6837\uff0c\u5728 RCC \u60a3\u8005\u7684\u5916\u5468\u8840\u548c\u80bf\u7624\u6d78\u6da6\u6dcb\u5df4\u7ec6\u80de\u7fa4\u4e2d\u53ef\u89c1\uff08FOXP3 +<\/sup>CD4 + <\/sup>CD25 +<\/sup> \uff09Treg \u6216\u80bf\u7624\u6d78\u6da6\u6027 PD-1 \u9633\u6027\u6dcb\u5df4\u7ec6\u80de\u6570\u91cf\u589e\u52a0\uff0c\u5e76\u4e14\u4e0e\u8f83\u5dee\u7684\u9884\u540e\u7ed3\u679c\u76f8\u5173 \u3002<\/p>\n

\u6b64\u5916\uff0c\u6dcb\u5df4\u7ec6\u80de\u6d78\u6da6\u4e2d NK \u7ec6\u80de\u7684\u6bd4\u4f8b\u5347\u9ad8\u9884\u793a\u7740 RCC \u7684\u9884\u540e\u8f83\u597d\u3002\u7d22\u62c9\u975e\u5c3c\u548c\u8212\u5c3c\u66ff\u5c3c\u5df2\u88ab\u8bc1\u660e\u53ef\u589e\u52a0\u80bf\u7624\u7ec6\u80de\u5bf9 NK \u7ec6\u80de\u6740\u4f24 RCC \u7ec6\u80de\u7684\u654f\u611f\u6027\u3002Choueiri \u7b49\u4eba\u5728\u6bd4\u8f83\u8212\u5c3c\u66ff\u5c3c\u548c\u5e15\u5511\u5e15\u5c3c\u4f5c\u4e3a mRCC \u60a3\u8005\u4e00\u7ebf\u6cbb\u7597\u7684 COMPARZ \u7814\u7a76\u7684\u5b50\u5206\u6790\u4e2d\uff0c\u663e\u793a\u589e\u52a0\u7684PD-L1\u80bf\u7624\u8868\u8fbe\u4ee5\u53ca\u80bf\u7624 CD8+<\/sup> T \u7ec6\u80de\u8ba1\u6570\u4e0e\u63a5\u53d7\u5e15\u5511\u5e15\u5c3c\u6216\u8212\u5c3c\u66ff\u5c3c\u6cbb\u7597\u7684\u60a3\u8005\u7684 OS \u8f83\u77ed\u6709\u5173\u3002<\/p>\n

\u6240\u6709\u8fd9\u4e9b\u6570\u636e\u90fd\u652f\u6301\u524d\u77bb\u6027\u8bd5\u9a8c\u8c03\u67e5\u7684\u7ed3\u679c\uff0c\u9a8c\u8bc1\u4e86 PD-L1 \u4f5c\u4e3a RCC TKI \u6cbb\u7597\u524d\u540e\u7684\u6f5c\u5728\u751f\u7269\u6807\u5fd7\u7269\u7684\u5fc5\u8981\u6027\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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21.3 RCC \u4e2d\u7684\u6297 PD-1 \u7814\u7a76<\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n

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21.3.1 \u2160\u671f\u8bd5\u9a8c<\/p>\n<\/section>\n

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\u7eb3\u6b66\u5229\u5c24\u5355\u6297 (Nivolumab) \u662f\u4e00\u79cd\u5bf9 PD-1 \u5177\u6709\u7279\u5f02\u6027\u963b\u65ad\u4f5c\u7528\u7684\u5168\u4eba\u6e90\u5355\u514b\u9686 IgG4 \u6297\u4f53\uff0c\u5176\u5b89\u5168\u6027\u548c\u8010\u53d7\u6027\u9996\u6b21\u5728\u4e00\u9879\u9488\u5bf9 39 \u540d\u60a3\u6709mRCC\u3001\u9ed1\u8272\u7d20\u7624\u3001\u7ed3\u76f4\u80a0\u764c\u3001\u53bb\u52bf\u62b5\u6297\u6027\u524d\u5217\u817a\u764c (CRPC) \u3001\u975e\u5c0f\u7ec6\u80de\u80ba\u764c (NSCLC) \u60a3\u8005\u7684 I \u671f\u5242\u91cf\u9012\u589e\u7814\u7a76\u4e2d\u5f97\u5230\u8bc1\u5b9e\u3002\u4e0d\u8fc7\u672c\u7814\u7a76\u4e2d\u53ea\u6709\u4e00\u540d\u60a3\u8005\u60a3\u6709 RCC\u3002<\/p>\n

\u5728\u4ee5 0.3\u30011\u30013 \u6216 10 mg\/kg \u5242\u91cf\u9012\u589e\u7684\u516d\u540d\u60a3\u8005\u961f\u5217\u540e\uff0c\u8be5\u7814\u7a76\u5728\u6700\u5927\u8010\u53d7\u5242\u91cf (MTD) \u6216 10 mg\/kg \u7684\u6269\u5c55\u961f\u5217\u4e2d\u62db\u52df\u4e86 15 \u540d\u60a3\u8005\u3002\u60a3\u8005\u63a5\u53d7\u4e00\u5242\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u5e76\u6bcf\u5468\u76d1\u6d4b\u6bd2\u6027\u3002\u5f71\u50cf\u5b66\u91cd\u65b0\u5206\u671f\u5728\u7b2c 8 \u5468\u548c\u7b2c 12 \u5468\u8fdb\u884c\u3002\u6ca1\u6709\u8fdb\u5c55\u6027\u75be\u75c5 (PD) \u6216 3 \u7ea7\u4e0d\u826f\u4e8b\u4ef6 (AE) \u7684\u60a3\u8005\u5728\u7b2c 12 \u5468\u548c\u7b2c 16 \u5468\u63a5\u53d7\u4e86\u989d\u5916\u5242\u91cf\uff08\u521d\u59cb\u5242\u91cf\uff09\u3002\u6ca1\u6709\u5242\u91cf\u9650\u5236\u8be5\u8bd5\u9a8c\u4e2d\u7684\u6bd2\u6027\uff08DLT\uff09\uff0c\u56e0\u6b64\u672a\u786e\u5b9a MTD\u3002\u6240\u4ee5\uff0c15 \u540d\u60a3\u8005\u7684\u6269\u5927\u961f\u5217\u4ee5 10 mg\/kg \u7684\u5242\u91cf\u5165\u7ec4\u3002\u603b\u4f53\u800c\u8a00\uff0c\u8be5\u836f\u7269\u8010\u53d7\u6027\u826f\u597d\uff0c\u6700\u5e38\u89c1\u7684 2 \u7ea7\u6216\u66f4\u9ad8\u6bd2\u6027\u662f CD4+<\/sup> \u6dcb\u5df4\u7ec6\u80de\u8ba1\u6570\u51cf\u5c11 (35.8%)\u3001\u6dcb\u5df4\u7ec6\u80de\u51cf\u5c11 (25.7%)\u3001\u808c\u8089\u75b2\u52b3 (15.4%) \u548c\u808c\u8089\u9aa8\u9abc\u75bc\u75db (15.4%)\u3002\u552f\u4e00\u7684 3 \u7ea7\u514d\u75ab\u76f8\u5173\u4e0d\u826f\u4e8b\u4ef6\u662f\u708e\u75c7\u6027\u7ed3\u80a0\u708e\uff08\u4e00\u540d\u60a3\u8005\uff09\uff0c\u5e76\u4e14\u5bf9\u76ae\u8d28\u7c7b\u56fa\u9187\u548c\u82f1\u592b\u5229\u6614\u5355\u6297\u6cbb\u7597\u53cd\u5e94\u826f\u597d\u3002\u603b\u4f53\u800c\u8a00\uff0c1 \u540d\u60a3\u8005 (2.5%) \u83b7\u5f97 CR\uff0c2 \u540d (5%) \u60a3\u8005\u83b7\u5f97 PR\uff0c2 \u540d (5%) \u60a3\u8005\u51fa\u73b0\u6df7\u5408\u53cd\u5e94\uff0c\u5b9a\u4e49\u4e3a\u67d0\u4e9b\u75c5\u53d8\u6d88\u9000\u800c\u5176\u4ed6\u75c5\u53d8\u540c\u65f6\u8fdb\u5c55\u3002\u72ec\u7279\u7684 RCC \u60a3\u8005\u5728\u63a5\u53d7 10 mg\/kg \u7684\u4e09\u5242\u540e PR \u5ef6\u957f\uff08\u8d85\u8fc7 16 \u4e2a\u6708\uff09\u3002<\/p>\n

\u5728\u4e00\u9879\u6269\u5927\u7684 I \u671f\u8bd5\u9a8c\u4e2d\u8fdb\u4e00\u6b65\u8bc1\u660e\u4e86\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u5728 RCC \u4e2d\u7684\u5b89\u5168\u6027\u548c\u6709\u6548\u6027\uff0c\u8be5\u8bd5\u9a8c\u62db\u52df\u4e86\u665a\u671f RCC\u3001NSCLC\u3001\u9ed1\u8272\u7d20\u7624\u3001\u7ed3\u76f4\u80a0\u764c\u6216 CRPC \u7684\u60a3\u8005\u3002\u8ba1\u5212\u5728 8 \u5468\u7684\u5468\u671f\u4e2d\u6bcf 2 \u5468 1.0\u30013.0 \u6216 10.0 mg\/kg \u7684\u8fde\u7eed\u7ed9\u836f\u3002\u7814\u7a76\u4e2d\u6ca1\u6709\u4f7f\u7528\u6700\u5927\u8010\u53d7\u5242\u91cf (MTD) \u6216 10 mg\/kg \u7684\u6269\u5c55\u961f\u5217\u3002\u6700\u7ec8\u7eb3\u5165\u4e86 296 \u540d\u60a3\u8005\uff0c\u5176\u4e2d 34 \u540d\u60a3\u8005\u60a3\u6709\u665a\u671f RCC\uff0c\u5e76\u4e14\u63a5\u53d7\u8fc7\u80be\u5207\u9664\u672f\u3001\u514d\u75ab\u6cbb\u7597\u548c\/\u6216 TKI \u6cbb\u7597\u3002\u5728\u8be5\u8bd5\u9a8c\u4e2d\uff0c\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u4f3c\u4e4e\u5177\u6709\u66f4\u597d\u7684\u5b89\u5168\u6027\uff1a296 \u540d\u60a3\u8005\u4e2d\u53ea\u6709 15 \u540d (5%) \u56e0 AE \u505c\u6b62\u6cbb\u7597\u3002\u603b\u5171\u6709 70% \u7684\u60a3\u8005\u8868\u73b0\u4e86\u4e0e\u6cbb\u7597\u76f8\u5173\u7684 AE\uff0c14% \u7684\u60a3\u8005\u8868\u73b0\u4e86 3 \u7ea7\u6216 4 \u7ea7\u4e8b\u4ef6\u3002\u5728\u81f3\u5c11 10% \u7684\u60a3\u8005\u4e2d\u53d1\u751f\u7684\u552f\u4e00\u4e0e\u6cbb\u7597\u76f8\u5173\u7684 AE \u662f\u808c\u8089\u75b2\u52b3 (24%)\u3001\u76ae\u75b9 (12%)\u3001\u8179\u6cfb (11%) \u548c\u7619\u75d2 (10%)\u3002\u53d1\u751f\u4e0d\u8d85\u8fc7 1% \u7684 3\/4 \u7ea7\u6cbb\u7597\u76f8\u5173\u6bd2\u6027\u3002\u73b0\u5b9e\u4e2d\u4e0d\u5e38\u89c1\u4e25\u91cd\u7684\u514d\u75ab\u76f8\u5173 AE \uff0c\u4ec5\u5728\u4e0d\u5230 1% \u7684\u63a5\u53d7\u6cbb\u7597\u7684\u60a3\u8005\u4e2d\u89c2\u5bdf\u5230\u3002\u7136\u800c\uff0c\u5728 NSCLC\uff082 \u540d\u60a3\u8005\uff09\u548c\u7ed3\u76f4\u80a0\u764c\uff081 \u540d\u60a3\u8005\uff09\u7ec4\u4e2d\u53d1\u751f\u4e86 3 \u4f8b\u7ee7\u53d1\u4e8e\u80ba\u708e\u7684\u836f\u7269\u76f8\u5173\u6b7b\u4ea1\u3002<\/p>\n

\u5728\u6240\u6709\u6d4b\u8bd5\u5242\u91cf\u4e2d\u5747\u89c2\u5bdf\u5230\u6297\u80bf\u7624\u6d3b\u6027\u3002\u6574\u4e2a RCC \u961f\u5217\u7684 ORR \u4e3a 27%\u30025 \u540d\u5728\u6570\u636e\u5206\u6790\u524d 1 \u5e74\u4ee5\u4e0a\u5f00\u59cb\u6cbb\u7597\u5e76\u8fbe\u5230\u5ba2\u89c2\u7f13\u89e3\u7684\u60a3\u8005\u5177\u6709\u81f3\u5c11 1 \u5e74\u7684\u6301\u4e45\u7f13\u89e3\u3002RCC \u961f\u5217\u5728 24 \u5468\u65f6\u7684 PFS \u4e3a 56%\u3002\u4e09\u5e74\u540e\uff0c\u6700\u540e\u4e00\u540d\u60a3\u8005\u5728\u968f\u540e\u7684\u62a5\u544a\u4e2d\u53c2\u52a0\u4e86\u8fd9\u9879\u6269\u5927\u7684 I \u671f\u7814\u7a76\uff1b34 \u540d\u60a3\u8005 mRCC \u961f\u5217\u62a5\u544a\u4e86\u989d\u5916\u7684\u7597\u6548\u3001\u5b58\u6d3b\u7387\u548c\u957f\u671f\u5b89\u5168\u6027\u3002\u5728\u5206\u6790\u65f6\uff0c\u751f\u5b58\u968f\u8bbf\u7684\u534a\u6570\u751f\u5b58\u671f\uff08\u4e2d\u4f4d\u751f\u5b58\u671f\uff09\u4e3a 45.2 \u4e2a\u6708\uff08\u8303\u56f4\uff0c25.9-57.9\uff09\u3002<\/p>\n

\u603b\u4f53\u800c\u8a00\uff0c34 \u540d\u60a3\u8005\u4e2d\u6709 10 \u540d\uff0829%\uff09\u51fa\u73b0\u5ba2\u89c2\u53cd\u5e94\u3002\u4e2d\u4f4d\u53cd\u5e94\u6301\u7eed\u65f6\u95f4\u4e3a 16 \u5468\uff08\u8303\u56f4\u4e3a 8-48 \u5468\uff09\u300240% \u7684\u54cd\u5e94\u8005\u5728\u7b2c 8 \u5468\uff08\u7b2c\u4e00\u6b21\u653e\u5c04\u5f71\u50cf\u5b66\u8bc4\u4f30\uff09\u65f6\u8fbe\u5230\u4e86\u54cd\u5e94\uff0c\u5927\u591a\u6570\uff0870%\uff09\u5728 16 \u5468\u65f6\u8fbe\u5230\u4e86\u54cd\u5e94\u3002\u4e2d\u4f4d\u53cd\u5e94\u6301\u7eed\u65f6\u95f4\u4e3a 12.9 \u4e2a\u6708\u3002\u5341\u540d\u54cd\u5e94\u8005\u4e2d\u6709\u4e94\u540d\u56e0 PD \u4ee5\u5916\u7684\u539f\u56e0\u505c\u6b62\u6cbb\u7597\u3002\u5176\u4e2d\u56db\u540d\u60a3\u8005\u63a5\u53d7\u4e86\u6cbb\u7597\uff0c\u6301\u7eed\u53cd\u5e94\u65f6\u95f4\u4e3a 19 \u81f3 56 \u5468\u4ee5\u4e0a\u3002\u9664\u4e86\u6709\u5ba2\u89c2\u53cd\u5e94\u7684 10 \u540d (29%) \u60a3\u8005\u5916\uff0c9 \u540d (27%) \u7684\u60a3\u8005\u75c5\u60c5\u7a33\u5b9a (SD) \u81f3\u5c11 24 \u5468\u3002\u5728\u5206\u6790\u65f6\uff0c34 \u540d\u60a3\u8005\u4e2d\u6709 19 \u540d\uff0856%\uff09\u6b7b\u4ea1\u3002\u4e2d\u4f4d OS \u4e3a 22.4 \u4e2a\u6708\uff0895% CI\uff0c12.5\u2013NR\uff09\u30023\u5e74\u751f\u5b58\u7387\u4e3a44%\u3002\u4e2d\u4f4d PFS \u4e3a 7.3 \u4e2a\u6708\uff0895% CI\uff0c3.6-10.9\uff09\uff0c2 \u5e74 PFS \u7387\u4e3a 12%\u3002<\/p>\n

\u603b\u4f53\u800c\u8a00\uff0c85% (29\/34) \u7684\u60a3\u8005\u62a5\u544a\u4e86\u4efb\u4f55\u7ea7\u522b\u7684\u6cbb\u7597\u76f8\u5173 AE\u3002\u6700\u5e38\u89c1\u7684\u662f\u808c\u8089\u75b2\u52b3 (41%)\u3001\u76ae\u75b9 (27%)\u3001\u8179\u6cfb (14%) \u548c\u7619\u75d2 (14%)\u30026 \u540d (18%) \u60a3\u8005\u62a5\u544a\u4e86 3 \u7ea7\u6216 4 \u7ea7\u6cbb\u7597\u76f8\u5173 AE\uff0c\u4f46\u8fd9\u4e9b AE \u662f\u53ef\u9006\u7684\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

\n

21.3.2 \u2161\u671f\u8bd5\u9a8c<\/p>\n<\/section>\n

\n
\n
\n

\u57fa\u4e8e\u6709\u6548\u7684\u6bd2\u6027\u6570\u636e\u548c I \u671f\u8bd5\u9a8c\u4e2d\u6709\u5e0c\u671b\u7684\u7597\u6548\uff0c\u8fdb\u884c\u4e86\u4e00\u9879\u4f7f\u7528\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u7684\u968f\u673a II \u671f\u8bd5\u9a8c\u3002168 \u540d\u60a3\u8005\u968f\u673a\u63a5\u53d7\u6bcf 3 \u5468\u4e00\u6b21\u7684\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u6cbb\u7597\uff0c\u5242\u91cf\u4e3a 3 \u79cd\u4e0d\u540c\u5242\u91cf\uff1a0.3 mg\/kg\uff0860 \u540d\u60a3\u8005\uff09\u30012 mg\/kg\uff0854 \u540d\u60a3\u8005\uff09\u6216 10 mg\/kg\uff0854 \u540d\u60a3\u8005\uff09\u4e00\u6b21\u3002\u4e3b\u8981\u7ec8\u70b9\u662f\u6bd4\u8f83\u4e0d\u540c\u5242\u91cf\u7ec4\u7684 PFS\uff0c\u4ee5\u786e\u5b9a\u662f\u5426\u5b58\u5728\u5242\u91cf\u53cd\u5e94\u5173\u7cfb\u3002\u6b21\u8981\u7ec8\u70b9\u5305\u62ec ORR\u3001OS\u3001\u53cd\u5e94\u65f6\u95f4\u3001\u53cd\u5e94\u6301\u7eed\u65f6\u95f4\u548c\u5b89\u5168\u6027\u3002 <\/p>\n

PFS \u6ca1\u6709\u5242\u91cf\u53cd\u5e94\u5173\u7cfb\uff0c\u4e2d\u4f4d PFS \u4e3a 2.7 \u4e2a\u6708\uff0880% CI\uff0c1.9-3.0\uff09\u30014.0 \u4e2a\u6708\uff0880% CI\uff0c2.8-4.2\uff09\u548c 4.2 \u4e2a\u6708\uff0880% CI\uff0c2.8-5.5\uff09\u5206\u522b\u4e3a 0.3\u30012 \u548c 10 mg\/kg \u7ec4\uff08p \u503c 0.9\uff09\u30020.3 mg\/kg \u7ec4\u7684 ORR \u4e3a 20%\uff0c2 mg\/kg \u7ec4\u4e3a 22%\uff0c10 mg\/kg \u7ec4\u4e3a 20%\uff08p \u503c 1.0\uff09\u3002\u6240\u6709\u7ec4\u7684\u53cd\u5e94\u65f6\u95f4\u76f8\u4f3c\uff0c\u4e2d\u4f4d\u6570\u4e3a 2.8-3.0 \u4e2a\u6708\uff0c\u8303\u56f4\u4e3a 1.3-10 \u4e2a\u6708\u30020.3 mg\/kg \u548c 2 mg\/kg \u7ec4\u672a\u8fbe\u5230\u7f13\u89e3\u6301\u7eed\u65f6\u95f4 (NR)\uff0c\u4f46 10 mg\/kg \u7ec4\u4e3a 22.3 \u4e2a\u6708 (80% CI, 4.8\u2013NR)\u30020.3 mg\/kg \u7ec4\u7684\u4e2d\u4f4d OS \u4e3a 18.2 \u4e2a\u6708 (80% CI, 16.2\u201324.0)\uff0c2 mg\/kg \u7ec4\u4e3a 25.5 \u4e2a\u6708 (80% CI, 19.8\u201328.8)\uff0c\u4ee5\u53ca 24.7 (80% CI, 15.3\u2013 26.0) \u5728 10 mg\/kg \u7ec4\u4e2d\u3002<\/p>\n

\u5728\u5206\u6790\u65f6\uff0c\u572835 \u540d\u6709\u5ba2\u89c2\u53cd\u5e94\u7684\u60a3\u8005\u4e2d\u6709 40% \u5728\u6cbb\u7597\u5f00\u59cb\u540e\u81f3\u5c11 24 \u4e2a\u6708\u4ecd\u6709\u53cd\u5e94\u300273% \u7684\u60a3\u8005\u62a5\u544a\u4e86\u81f3\u5c11\u4e00\u79cd\u4e0e\u6cbb\u7597\u76f8\u5173\u7684 AE\uff0c19 \u540d\uff0811%\uff09\u60a3\u8005\u7ecf\u5386\u4e86 3 \u7ea7\u6216 4 \u7ea7\u6cbb\u7597\u76f8\u5173\u7684 AE\u3002\u808c\u8089\u75b2\u52b3\u662f\u6700\u5e38\u62a5\u544a\u7684 AE\uff0881% \u7684\u60a3\u8005\uff09\u3002\u4e00\u822c\u800c\u8a00\uff0c\u5404\u961f\u5217\u4e2d\u6cbb\u7597\u76f8\u5173 AE \u7684\u53d1\u751f\u7387\u6ca1\u6709\u663e\u7740\u5dee\u5f02\u3002\u6ca1\u6709 3 \u7ea7\u6216 4 \u7ea7\u80ba\u708e\u75c5\u4f8b\u3002\u6cbb\u7597\u76f8\u5173\u7684 AE \u5bfc\u81f4 11 \u540d\u60a3\u8005 (7%) \u505c\u836f\u3002\u5728 0.3\u30012 \u548c 10 mg\/kg \u7ec4\u4e2d\uff0c\u5206\u522b\u6709 1 \u540d (2%)\u30016 \u540d (11%) \u548c 4 \u540d (7%) \u60a3\u8005\u56e0\u6cbb\u7597\u76f8\u5173 AE \u505c\u6b62\u6cbb\u7597\u3002\u5bfc\u81f4\u505c\u836f\u7684\u6cbb\u7597\u76f8\u5173 AE \u6d89\u53ca\u5fc3\u810f\u3001\u5185\u5206\u6ccc\u3001\u547c\u5438\u3001\u80f8\u90e8\u6216\u795e\u7ecf\u7cfb\u7edf\u75be\u75c5\u3002<\/p>\n

\u4e0e I \u671f\u8bd5\u9a8c\u76f8\u6bd4\uff0c\u2161\u671f\u6ca1\u6709\u4e0e\u6cbb\u7597\u76f8\u5173\u7684\u6b7b\u4ea1\u3002\u603b\u4e4b\uff0c\u968f\u673a II \u671f\u8bd5\u9a8c\u8868\u660e\uff0c\u7ecf\u8fc7\u5927\u91cf\u9884\u5904\u7406\u7684 mRCC \u60a3\u8005\u53ef\u4ee5\u5728\u5b89\u5168\u8303\u56f4\u5185\u8010\u53d7\u7eb3\u6b66\u5229\u5c24\u5355\u6297\uff0cORR \u4e3a 20-22%\uff0c40% \u7684\u53cd\u5e94\u8005\u6301\u7eed\u53cd\u5e94\u8d85\u8fc7 2 \u5e74\u30020.3\u30012 \u548c 10 mg\/kg \u7ec4\u4e4b\u95f4\u6ca1\u6709\u5242\u91cf\u53cd\u5e94\u5173\u7cfb\uff0c\u6240\u6709\u7ec4\u7684\u5b89\u5168\u6027\u90fd\u662f\u53ef\u63a7\u7684\u3002<\/p>\n

\u57fa\u4e8e I \u671f\u548c II \u671f\u8bd5\u9a8c\u4e2d\u5404\u79cd\u7ed9\u836f\u7ec4\u5408\u7684\u4e34\u5e8a\u7597\u6548\u548c\u5b89\u5168\u6027\uff0c\u9009\u62e9\u4ee5\u6bcf 2 \u5468 3 mg\/kg \u7684\u5242\u91cf\u8fdb\u884c\u5176\u4ed6\u7814\u7a76\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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21.3.3 \u2162\u671f\u8bd5\u9a8c<\/p>\n<\/section>\n

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CheckMate 025 \u7814\u7a76\u662f\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u4e0e\u4f9d\u7ef4\u83ab\u53f8\u5728\u665a\u671f RCC \u60a3\u8005\u4e2d\u7684 III \u671f\u968f\u673a\u8bd5\u9a8c\u3002821 \u540d\u65e2\u5f80\u63a5\u53d7\u8fc7\u81f3\u5c11\u4e00\u79cd\uff0872% \u7684\u60a3\u8005\uff09\u4f46\u4e0d\u8d85\u8fc7 2 \u79cd TKI \u6cbb\u7597\u7684\u665a\u671f RCC \u60a3\u8005\u4ee5 1:1 \u7684\u6bd4\u4f8b\u968f\u673a\u63a5\u53d7 3mg\/kg \u7684\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u6cbb\u7597\uff0c\u6bcf 2 \u546860\u5206\u949f\u9759\u8109\u8f93\u6ce8\uff0c\u4e1410 mg \u53e3\u670d\u4f9d\u7ef4\u83ab\uff0c\u76f4\u5230\u75be\u75c5\u8fdb\u5c55\u6216\u4e0d\u53ef\u63a5\u53d7\u7684\u6bd2\u6027\u3002\u8bd5\u9a8c\u7684\u4e3b\u8981\u76ee\u6807\u662fOS\u3002\u5173\u952e\u7684\u6b21\u8981\u76ee\u6807\u5305\u62ec ORR\u3001\u7814\u7a76\u8005\u786e\u5b9a\u7684 PFS \u548c\u7f13\u89e3\u6301\u7eed\u65f6\u95f4 (DoR)\u3002\u622a\u81f3 2015 \u5e74 6 \u6708 18 \u65e5\u8bd5\u9a8c\u622a\u6b62\u65e5\u671f\uff0c\u5f53 398 \u4f8b\u6b7b\u4ea1\uff08\u6700\u7ec8\u5206\u6790\u7684\u8ba1\u5212\u4e8b\u4ef6\u6570\u7684 70%\uff09\u53d1\u751f\u65f6\uff0c\u8fdb\u884c\u4e86\u4e2d\u671f OS \u5206\u6790\u3002<\/p>\n

\u4e0e\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u7ec4\u60a3\u8005\u7684 OS \u76f8\u6bd4\uff0c\u6709\u7edf\u8ba1\u5b66\u610f\u4e49\u7684\u6539\u5584\u4f9d\u7ef4\u83ab\u53f8\u7ec4\u60a3\u8005\u7684\u4e2d\u4f4d OS \u5dee\u5f02\u4e3a 5.4 \u4e2a\u6708\uff08\u4ece 19.6 \u4e2a\u6708\u5230 25.0 \u4e2a\u6708\uff09\uff0cHR \u4e3a 0.73\uff0895% CI\uff0c0.60-0.89\uff1bp \u503c 0.0018\uff09\u3002\u6839\u636e\u7814\u7a76\u8005\u7684\u8bc4\u4f30\uff0cPFS \u8bc1\u5b9e\uff0c\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u7ec4\u548c\u4f9d\u7ef4\u83ab\u53f8\u7ec4\u7684 ORR \u5206\u522b\u4e3a 21.5% \u548c 3.9%\uff0c\u4e2d\u4f4d\u7f13\u89e3\u6301\u7eed\u65f6\u95f4\u5206\u522b\u4e3a 23.0 \u4e2a\u6708\u548c 13.7 \u4e2a\u6708\u3002\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u7ec4\u7684 ORR \u9ad8\u4e8e\u4f9d\u7ef4\u83ab\u53f8\u7ec4\uff0825% vs 5%\uff1b\u4f18\u52bf\u6bd4 5.98\uff1b95% CI\uff0c3.68-9.72\uff1bp \u503c < 0.001\uff09\u3002<\/p>\n

\u5728\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u7ec4\u6709\u53cd\u5e94\u7684\u60a3\u8005\u4e2d\uff0c31% \u7684\u6cbb\u7597\u53cd\u5e94\u8d85\u8fc7 12 \u4e2a\u6708\u3002\u6700\u540e\uff0c\u4e24\u7ec4\u53cd\u5e94\u7684\u4e2d\u4f4d\u65f6\u95f4\u4f3c\u4e4e\u76f8\u4f3c\u3002\u5728 OS \u5206\u6790\u65f6\uff0c\u8fd8\u68c0\u67e5\u4e86\u6bcf\u4e2a\u7814\u7a76\u8005\u8bc4\u4f30\u7684 PFS\u3002\u89c2\u5bdf\u5230\u4e24\u4e2a\u6cbb\u7597\u7ec4\u4e4b\u95f4\u7684 PFS \u6ca1\u6709\u7edf\u8ba1\u5b66\u4e0a\u7684\u663e\u7740\u5dee\u5f02\u3002\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u7ec4\u7684\u4e2d\u4f4d PFS \u4e3a 4.6 \u4e2a\u6708\uff0c\u4f9d\u7ef4\u83ab\u53f8\u7ec4\u4e3a 4.4 \u4e2a\u6708\u3002\u5206\u5c42 HR \u4e3a 0.88\uff0895% CI\uff0c0.75-1.03\uff09\uff0c\u53cc\u8fb9\u5bf9\u6570\u79e9 p \u503c\u4e3a 0.11\u3002\u8003\u8651\u5230\u4e9a\u7ec4\u5206\u6790\uff0c\u5bf9\u4e8e MSKCC \u98ce\u9669\u8f83\u4f4e\u7684\u60a3\u8005\uff0c\u503c\u5f97\u6ce8\u610f\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u4e0e\u4f9d\u7ef4\u83ab\u53f8\u7684\u597d\u5904\uff08HR 0.48\uff0c95% CI 0.32\u20130.70\uff09\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n

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\u672c\u7814\u7a76\u4e2d\u7684\u526f\u4f5c\u7528\uff1a\u63a5\u53d7\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u6cbb\u7597\u7684\u60a3\u8005\u4e2d\u6709 79% \u6709\u6cbb\u7597\u76f8\u5173 AE\uff0c\u901a\u5e38\u662f\u808c\u8089\u75b2\u52b3\u3001\u6076\u5fc3\u548c\u7619\u75d2\u3002\u53ea\u6709 19% \u7684\u60a3\u8005\u51fa\u73b0 3 \u7ea7\u6216 4 \u7ea7 AE\uff082% \u7684\u8d2b\u8840\u548c 1% \u7684\u75b2\u52b3\u3001\u80ba\u708e\u548c\u8179\u6cfb\uff09\u300216% \u7684\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u6cbb\u7597\u60a3\u8005\u548c 19% \u4f9d\u7ef4\u83ab\u53f8\u6cbb\u7597\u7684\u60a3\u8005\u56e0\u4e0d\u826f\u53cd\u5e94\u505c\u6b62\u7814\u7a76\u6cbb\u7597\u3002\u63a5\u53d7\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u6cbb\u7597\u7684\u60a3\u8005\u4e2d\u6709 44% \u56e0\u4e0d\u826f\u53cd\u5e94\u51fa\u73b0\u836f\u7269\u5ef6\u8fdf\u3002\u5bf9\u4e8e\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u6cbb\u7597\u7ec4\u6216\u4f7f\u7528\u6700\u540e\u4e00\u5242\u7814\u7a76\u836f\u7269\u540e\uff0c30 \u5929\u5185\u7684\u6b7b\u4ea1\u7387\u4e3a 4.7%\uff0c\u800c\u4f9d\u7ef4\u83ab\u53f8\u7ec4\u4e3a 8.6%\u3002\u6839\u636e\u672c\u7814\u7a76\u663e\u793a\u7684\u8bc1\u636e\uff0c2015 \u5e74 11 \u6708\uff0c\u7eb3\u6b66\u5229\u5c24\u5355\u6297\u83b7 FDA \u6279\u51c6\u7528\u4e8e\u5148\u524d\u7ecf\u8fc7\u6297\u8840\u7ba1\u751f\u6210\u6cbb\u7597\u540e\u7684\u665a\u671f\u80be\u764c\u6cbb\u7597\uff0c\u5e76\u4e8e 2016 \u5e74\u8fdb\u4e00\u6b65\u83b7 EMA \u6279\u51c6\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\u672c\u6587\u7531Oncolab\u5fae\u4fe1\u516c\u4f17\u53f7\u7ffb\u8bd1\u6574\u7406\u81eaOncoimmunology: A Practical Guide for Cancer Immunotherapy\uff0c\u4ec5\u7528\u4e8e\u5b66\u4e60\u4ea4\u6d41\u4f7f\u7528\uff0c\u5982\u9700\u8d2d\u4e70\u539f\u7248\u4e66\u7c4d\u53ef\u70b9\u51fb\u9605\u8bfb\u539f\u6587\u8d2d\u4e70\u3002<\/span>
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\u2014 THE  END \u2014<\/span><\/p>\n


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\u6765\u6e90 | Oncoimmunology: A Practical Guide <\/span><\/section>\n
for Cancer Immunotherapy<\/span><\/section>\n
\u4f5c\u8005 | <\/span>Annette Paschen and Dirk Schadendorf<\/span><\/section>\n
\u521d\u7a3f\u7ffb\u8bd1 | \u9648\u6653\u610f \u5218\u6653\u9896 \u90d1\u68a6\u6021<\/span><\/span><\/section>\n
\u7f16\u8f91\u6392\u7248<\/span> | \u738b\u5b9a\u4e1a<\/span><\/span><\/span><\/section>\n
\u5ba1\u6838\u4fee\u6539 | \u738b\u5764 \u80e1\u73ca<\/span><\/section>\n
\uff08\u8f6c\u8f7d\u8bf7\u4fdd\u7559\u6b64\u90e8\u5206\u5185\u5bb9\uff09<\/span><\/strong><\/section>\n


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\u2589  \u5f3a\u70c8\u63a8\u8350<\/strong><\/strong><\/section>\n
\u2589  \u5f80\u671f\u6587\u7ae0\u5408\u8f91<\/strong><\/strong><\/section>\n

\u80bf\u7624\u514d\u75ab\u5b66\u6700\u65b0\u6587\u732e\u6bcf\u6708\u66f4\u65b0<\/span><\/a><\/a><\/a>
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\u514d\u75ab\u5b66\u62fe\u9057\u7cfb\u5217<\/span><\/a><\/p>\n

\u80bf\u7624\u514d\u75ab\u5b66\u7cfb\u5217<\/span><\/a>
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ACIR\u6587\u732e\u901f\u9012<\/span><\/a>
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SCI\u8bba\u6587\u4f5c\u56fe<\/span><\/a>
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SCI\u8bba\u6587\u5199\u4f5c\u53ca\u6295\u7a3f<\/span><\/a>
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\u751f\u4fe1\u5165\u95e8\u5b66\u4e60\u7b14\u8bb0<\/span><\/a>
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R\u8bed\u8a00\u57fa\u7840\u4e0e\u5355\u7ec6\u80de\u5206\u6790\u5b9e\u6218\u89c6\u9891\u8bfe\u7a0b<\/span><\/a>
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\u751f\u7269\u5b66\u5b9e\u9a8c\u6280\u672f\u53ca\u5e38\u7528\u8f6f\u4ef6<\/span><\/a>
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RCIM\u4eea\u5668\u7b80\u4ecb\u53ca\u64cd\u4f5c\u89c6\u9891<\/span><\/a>
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\u5e38\u7528\u7535\u8111\u8f6f\u4ef6\u4f7f\u7528\u6559\u7a0b<\/a><\/span><\/p>\n

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\u2589  OncoLab\u5b9e\u9a8c\u5ba4\u7f51\u7ad9<\/strong><\/strong><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n
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\u7f51\u7ad9\u81ea\u5e26\u68c0\u7d22\u529f\u80fd\uff0c\u53ef\u4ee5\u6839\u636e\u5173\u952e\u8bcd\u8fdb\u884c\u68c0\u7d22<\/span>\uff0c\u5e76\u4e14\u53ef\u4ee5\u6839\u636e\u65e5\u671f\u53ca\u5185\u5bb9\u5206\u7c7b<\/span>\u8fdb\u884c\u67e5\u770b ,\u5927\u5bb6\u53ef\u4ee5\u6536\u85cf\u65b9\u4fbf\u5728\u7535\u8111\u4e0a\u67e5\u770b\u3002<\/p>\n

\u7f51\u5740\u662f\uff1aoncolab.cn<\/span><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\u2589  OncoLab\u5b66\u672f\u5bfc\u822a<\/strong><\/strong><\/section>\n
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\u7f51\u5740\u662f\uff1adh.<\/strong><\/span>oncolab.cn<\/span><\/strong><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\u2589  OncoLab\u77e5\u8bc6\u661f\u7403<\/strong><\/strong><\/section>\n<\/section>\n
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\u8be5\u661f\u7403\u7528\u4e8eOncoLab\u516c\u4f17\u53f7\u8bfb\u8005\u4ea4\u6d41\u5b66\u4e60\u4f7f\u7528\uff0c\u6c38\u4e45\u514d\u8d39<\/span>\u3002<\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

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\u672c\u7bc7\u6587\u7ae0\u6765\u6e90\u4e8e\u5fae\u4fe1\u516c\u4f17\u53f7:OncoLab<\/p>\n<\/blockquote>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

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