¨®??¨¨¨°¡Á¨¨e¨¦3_?¦Ì¨¦¨²¨¬??y?¡¤?a¡¤?¨¬??¨¢??¡ä¨²1o¨ª?
¨®??¨¨?¦Ì¨¦¨²¨¬?¡ä¨®¨°?¡¤?¨¬¨¢1??y?¡¤¨®??¨¨¨°¡Á¨¨e¨¦3?????¡éD¡ì1??¡é¨¢?D¡ì¦Ì¨¨?a¨º?¡ê?2¡é¨®D¡À??Y??D¡ì¦Ì?¡ä¨²1o¡¤t??¡ê??¨¹¨®D?????y?¡¤?1¡ã?¨°?¨®??¨¨?a¨¨y¡ä¨²o¨ªAZD9291¨°?1??????????¡ê
¨®??¨¨¨°¡Á¨¨e¨¦3????_20181¨´¡¤?¨º???_?¦Ì¨¦¨²¨¬?
¨®??¨¨?¦Ì¨¦¨²¨¬?¡ä¨®¨°?¡¤?¨¬¨¢1??y?¡¤¨®??¨¨¨°¡Á¨¨e¨¦3?????¡éD¡ì1??¡é¨¢?D¡ì¦Ì¨¨?a¨º?¡ê?2¡é¨®D¡À??Y??D¡ì¦Ì?¡ä¨²1o¡¤t??¡ê??¨¹¨®D?????y?¡¤?1¡ã?¨°?¨®??¨¨?a¨¨y¡ä¨²o¨ªAZD9291¨°?1??????????¡ê
¨®??¨¨¨°¡Á¨¨e¨¦31o?¨°¡ä¨²1o¨¢¡Â3¨¬_?¦Ì¨¦¨²¨¬?
¨®??¨¨?¦Ì¨¦¨²¨¬?¡ä¨®¨°?¡¤?¨¬¨¢1??y?¡¤¨®??¨¨¨°¡Á¨¨e¨¦3?????¡éD¡ì1??¡é¨¢?D¡ì¦Ì¨¨?a¨º?¡ê?2¡é¨®D¡À??Y??D¡ì¦Ì?¡ä¨²1o¡¤t??¡ê??¨¹¨®D?????y?¡¤?1¡ã?¨°?¨®??¨¨?a¨¨y¡ä¨²o¨ªAZD9291¨°?1??????????¡ê
¨®??¨¨¨°¡Á¨¨e¨¦31|D¡ìD¡ì1?_?¦Ì¨¦¨²¨¬?
¨®??¨¨?¦Ì¨¦¨²¨¬?¡ä¨®¨°?¡¤?¨¬¨¢1??y?¡¤¨®??¨¨¨°¡Á¨¨e¨¦3?????¡éD¡ì1??¡é¨¢?D¡ì¦Ì¨¨?a¨º?¡ê?2¡é¨®D¡À??Y??D¡ì¦Ì?¡ä¨²1o¡¤t??¡ê??¨¹¨®D?????y?¡¤?1¡ã?¨°?¨®??¨¨?a¨¨y¡ä¨²o¨ªAZD9291¨°?1??????????¡ê
¨®??¨¨¨°¡Á¨¨e¨¦3???¨´??¡Àe¡¤?¡¤¡§_?¦Ì¨¦¨²¨¬?
¨®??¨¨?¦Ì¨¦¨²¨¬?¡ä¨®¨°?¡¤?¨¬¨¢1??y?¡¤¨®??¨¨¨°¡Á¨¨e¨¦3?????¡éD¡ì1??¡é¨¢?D¡ì¦Ì¨¨?a¨º?¡ê?2¡é¨®D¡À??Y??D¡ì¦Ì?¡ä¨²1o¡¤t??¡ê??¨¹¨®D?????y?¡¤?1¡ã?¨°?¨®??¨¨?a¨¨y¡ä¨²o¨ªAZD9291¨°?1??????????¡ê
¨®??¨¨¨°¡Á¨¨e¨¦3_?¦Ì¨¦¨²¨¬?
¨®??¨¨?¦Ì¨¦¨²¨¬?¡ä¨®¨°?¡¤?¨¬¨¢1??y?¡¤¨®??¨¨¨°¡Á¨¨e¨¦3?????¡éD¡ì1??¡é¨¢?D¡ì¦Ì¨¨?a¨º?¡ê?2¡é¨®D¡À??Y??D¡ì¦Ì?¡ä¨²1o¡¤t??¡ê??¨¹¨®D?????y?¡¤?1¡ã?¨°?¨®??¨¨?a¨¨y¡ä¨²o¨ªAZD9291¨°?1??????????¡ê
2¨²?¡¤?DD?_?¦Ì¨¦¨²¨¬?
¨®??¨¨?¦Ì¨¦¨²¨¬?¡ä¨®¨°?¡¤?¨¬¨¢1??y?¡¤¨®??¨¨¨°¡Á¨¨e¨¦3?????¡éD¡ì1??¡é¨¢?D¡ì¦Ì¨¨?a¨º?¡ê?2¡é¨®D¡À??Y??D¡ì¦Ì?¡ä¨²1o¡¤t??¡ê??¨¹¨®D?????y?¡¤?1¡ã?¨°?¨®??¨¨?a¨¨y¡ä¨²o¨ªAZD9291¨°?1??????????¡ê
¨°¡Á¨¨e¨¦3_?a¨¨y¡ä¨²_AZD9291¡ä¨²1o¨¢¡Â3¨¬_¨®??¨¨?¦Ì¨¦¨²¨¬?
¨®??¨¨?¦Ì¨¦¨²¨¬?¡ä¨®¨°?¡¤?¨¬¨¢1??y?¡¤¨®??¨¨¨°¡Á¨¨e¨¦3?????¡éD¡ì1??¡é¨¢?D¡ì¦Ì¨¨?a¨º?¡ê?2¡é¨®D¡À??Y??D¡ì¦Ì?¡ä¨²1o¡¤t??¡ê??¨¹¨®D?????y?¡¤?1¡ã?¨°?¨®??¨¨?a¨¨y¡ä¨²o¨ªAZD9291¨°?1??????????¡ê
¨®??¨¨?¦Ì¨¦¨²¨¬?¡ä¨®¨°?¡¤?
¨®??¨¨?¦Ì¨¦¨²¨¬?¡ä¨®¨°?¡¤?¨¬¨¢1??y?¡¤¨®??¨¨¨°¡Á¨¨e¨¦3?????¡éD¡ì1??¡é¨¢?D¡ì¦Ì¨¨?a¨º?¡ê?2¡é¨®D¡À??Y??D¡ì¦Ì?¡ä¨²1o¡¤t??¡ê??¨¹¨®D?????y?¡¤?1¡ã?¨°?¨®??¨¨?a¨¨y¡ä¨²o¨ªAZD9291¨°?1??????????¡ê


¡¤?¡ã?¡ãD?¨°¨°?¨¨y¡Á??|¨¢¡é¡ê?¨°¡Á¨¨e¨¦3?¡é¨¬??T?-?¡é?-?¨¤?¨¦_?¦Ì¨¦¨²¨¬?
¨®??¨¨?¦Ì¨¦¨²¨¬?¡ä¨®¨°?¡¤?¨¬¨¢1??y?¡¤¨®??¨¨¨°¡Á¨¨e¨¦3?????¡éD¡ì1??¡é¨¢?D¡ì¦Ì¨¨?a¨º?¡ê?2¡é¨®D¡À??Y??D¡ì¦Ì?¡ä¨²1o¡¤t??¡ê??¨¹¨®D?????y?¡¤?1¡ã?¨°?¨®??¨¨?a¨¨y¡ä¨²o¨ªAZD9291¨°?1??????????¡ê
¨°¡Á¨¨e¨¦3¡ãD?¨°??¨¢??????¨º¡ä?¦Ì?60¡ê£¤??70¡ê£¤_?¦Ì¨¦¨²¨¬?
¨®??¨¨?¦Ì¨¦¨²¨¬?¡ä¨®¨°?¡¤?¨¬¨¢1??y?¡¤¨®??¨¨¨°¡Á¨¨e¨¦3?????¡éD¡ì1??¡é¨¢?D¡ì¦Ì¨¨?a¨º?¡ê?2¡é¨®D¡À??Y??D¡ì¦Ì?¡ä¨²1o¡¤t??¡ê??¨¹¨®D?????y?¡¤?1¡ã?¨°?¨®??¨¨?a¨¨y¡ä¨²o¨ªAZD9291¨°?1??????????¡ê
¨®??¨¨¨°¡Á¨¨e¨¦3??¡Áa¨°?D??¡À3|¡ã?¦Ì???¨¢?_?¦Ì¨¦¨²¨¬?
¨®??¨¨?¦Ì¨¦¨²¨¬?¡ä¨®¨°?¡¤?¨¬¨¢1??y?¡¤¨®??¨¨¨°¡Á¨¨e¨¦3?????¡éD¡ì1??¡é¨¢?D¡ì¦Ì¨¨?a¨º?¡ê?2¡é¨®D¡À??Y??D¡ì¦Ì?¡ä¨²1o¡¤t??¡ê??¨¹¨®D?????y?¡¤?1¡ã?¨°?¨®??¨¨?a¨¨y¡ä¨²o¨ªAZD9291¨°?1??????????¡ê
¨°¡Á¨¨e¨¦3??¨¢?¡¤?¡ã?D¨¨¡Á?EGFR?¨´¨°¨°¨ª?¡À??¨¬2a_?¦Ì¨¦¨²¨¬?
¨®??¨¨?¦Ì¨¦¨²¨¬?¡ä¨®¨°?¡¤?¨¬¨¢1??y?¡¤¨®??¨¨¨°¡Á¨¨e¨¦3?????¡éD¡ì1??¡é¨¢?D¡ì¦Ì¨¨?a¨º?¡ê?2¡é¨®D¡À??Y??D¡ì¦Ì?¡ä¨²1o¡¤t??¡ê??¨¹¨®D?????y?¡¤?1¡ã?¨°?¨®??¨¨?a¨¨y¡ä¨²o¨ªAZD9291¨°?1??????????¡ê
























2018?¨º¨°¡Á¨¨e¨¦3¡Á?D?¡ã¨¹¡Á¡ã_?¦Ì¨¦¨²¨¬?
¨®??¨¨?¦Ì¨¦¨²¨¬?¡ä¨®¨°?¡¤?¨¬¨¢1??y?¡¤¨®??¨¨¨°¡Á¨¨e¨¦3?????¡éD¡ì1??¡é¨¢?D¡ì¦Ì¨¨?a¨º?¡ê?2¡é¨®D¡À??Y??D¡ì¦Ì?¡ä¨²1o¡¤t??¡ê??¨¹¨®D?????y?¡¤?1¡ã?¨°?¨®??¨¨?a¨¨y¡ä¨²o¨ªAZD9291¨°?1??????????¡ê






















































































































AZD9291_?¦Ì¨¦¨²¨¬??y?¡¤¡ã??¡ê¨¬??¨¢????¨ª?
¨®??¨¨?¦Ì¨¦¨²¨¬?¡ä¨®¨°?¡¤?¨¬¨¢1??y?¡¤¨®??¨¨¨°¡Á¨¨e¨¦3?????¡éD¡ì1??¡é¨¢?D¡ì¦Ì¨¨?a¨º?¡ê?2¡é¨®D¡À??Y??D¡ì¦Ì?¡ä¨²1o¡¤t??¡ê??¨¹¨®D?????y?¡¤?1¡ã?¨°?¨®??¨¨?a¨¨y¡ä¨²o¨ªAZD9291¨°?1??????????¡ê
¨®??¨¨?a¨¨y¡ä¨²_?¦Ì¨¦¨²¨¬??y?¡¤¨°¨¢???3¨¦3¡ä¨²1o¨ª?
¨®??¨¨?¦Ì¨¦¨²¨¬?¡ä¨®¨°?¡¤?¨¬¨¢1??y?¡¤¨®??¨¨¨°¡Á¨¨e¨¦3?????¡éD¡ì1??¡é¨¢?D¡ì¦Ì¨¨?a¨º?¡ê?2¡é¨®D¡À??Y??D¡ì¦Ì?¡ä¨²1o¡¤t??¡ê??¨¹¨®D?????y?¡¤?1¡ã?¨°?¨®??¨¨?a¨¨y¡ä¨²o¨ªAZD9291¨°?1??????????¡ê








































































































































¨®??¨¨?a¨¨y¡ä¨²_?¦Ì¨¦¨²¨¬??y?¡¤¨°¨¢???3¨¦3¡ä¨²1o¨ª?
¨®??¨¨?¦Ì¨¦¨²¨¬?¡ä¨®¨°?¡¤?¨¬¨¢1??y?¡¤¨®??¨¨¨°¡Á¨¨e¨¦3?????¡éD¡ì1??¡é¨¢?D¡ì¦Ì¨¨?a¨º?¡ê?2¡é¨®D¡À??Y??D¡ì¦Ì?¡ä¨²1o¡¤t??¡ê??¨¹¨®D?????y?¡¤?1¡ã?¨°?¨®??¨¨?a¨¨y¡ä¨²o¨ªAZD9291¨°?1??????????¡ê