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WCLC 2017:盘点肺癌治疗的三个“新时代”

2017-10-20 良医汇通讯社 肿瘤资讯

肺癌治疗在过去的30年里,在全球医生的努力下不断进步,不断创新,经历了3个飞跃的新时代:化疗时代、靶向时代、免疫时代!就像我们的中国,从1949年解放后,也是经历建国初期的发展阶段、改革开放后的快速发展阶段、和即将到来的一个新时代!

肺癌治疗在过去的30年里,在全球医生的努力下不断进步,不断创新,经历了3个飞跃的新时代:化疗时代、靶向时代、免疫时代!就像我们的中国,从1949年解放后,也是经历建国初期的发展阶段、改革开放后的快速发展阶段、和即将到来的一个新时代!

1980's-2000 化疗药物出现,有证可循、解决温饱

化疗药物发展的历史也就是从1950‘s开始的,最早应用于血液肿瘤为主。1995年,一篇发表在BMJ上的meta分析显示,肺癌化疗联合BSC比单纯的最佳支持治疗(BSC)可以延长患者的生存。解析来,一系列的所谓三代肺癌化疗药物相继上市,也证明了含铂双药由于单药治疗。这些可以写进时代的化疗药物包括:顺铂、卡铂、长春瑞滨、紫杉醇、多西他赛、吉西他滨、培美曲塞。注明的ECOG1594研究证明,3代药物联合铂类治疗晚期非小细胞肺癌的疗效类似,化疗药物的治疗进入平台期。之后的的研究更多的是从1到100,缺乏突破性创新。




1995年发表在BMJ上的Meta分析

化疗药物的出现,解决的晚期肺癌无药可用的境况,但是疗效仅仅是强差人意而已。一线治疗的有效率在30-40%,中位的无疾病进展时间在5-6个月,并且细胞毒药物的副反应明显,需要强大的支持治疗。尽管医生试图找到预测化疗疗效的分子标志物,但是基本都无功而返。仅仅培美曲塞显示在非鳞的非小细胞肺癌中略有优势。



著名的ECOG1594研究

肺癌的医生为仅仅延长2-3个月的PFS和OS而欢呼雀跃,患者一直在为是否使用化疗还是不使用化疗之间而犹豫不决。这就像刚刚解放后的新中国,我们有饭可吃,但是没有营养和美味可谈,能吃到肉,就是幸福生活!

2000-2015 靶向时代,改革开放,让一部分病人活得长起来!

靶向治疗的开始,是从一个悲喜交加的故事开始,吉非替尼由于在2期临床中的优异表现,FDA提前通过审批给予上市,可是在接下来的验证性的III其临床中,吉非替尼经历了滑铁卢,被FDA撤市!

EGFR通路的三个重要研究者:林奇教授、莫树锦教授、吴一龙教授

由于中国专家吴一龙教授等发现该药在女性不吸烟的腺癌中疗效出众,吉非替尼在中国逆势而上。2004年,几乎同时,Thomas J. Lynch和J.Guillermo Paez在Science和NEJM上发表文章,发现EGFR TKI药物对EGFR突变的患者特别有效,EGFR突变可以预测EGFR TKI药物的疗效。也把中国肺癌的治疗水平提高到了国际前列。2007年,来自中国的莫树锦教授和吴一龙教授通过IPASS研究,前瞻性的证实了吉非替尼在EGFR的突变患者中的疗效,也拉开了肺癌精准治疗的大幕。接下来中国学者在EGFR突变肺癌上的研究更是势如破竹,OPTIMAL研究、INFORM研究、LUX-Lung3/6研究、AURA3研究、以及在早期肺癌辅助治疗的Adjuvent研究。在化疗时代,中国肺癌研究还处于一个学习和追随的阶段,而在肺癌的精准治疗时代,中国开始领跑世界前沿。


IPASS研究开始了肺癌精准治疗的新时代


吴一龙教授关于最新的关于EGFR辅助治疗肺癌的Adjuvent研究

靶向治疗的疗效相对于化疗有了质的飞跃,在精准人群中的有效率达到了70%,无疾病进展时间达到了12个月左右,安全性也是大幅提高。接下来对ALK通路的研究,对EGFR耐药后T790M的研究,肺癌被分成了不同驱动基因,在有药可治的有驱动基因的肺癌里,患者的生存时间大幅延长,后继耐药的机制和药物研究也是突飞猛进。

但是有驱动基因并且有药可用的肺癌的比例还不是特别的高,EGFR的突变大约30%左右,EGFR耐药后的T790M突变是50%左右,ALK突变的比例是2-3%,ROS-1突变只有1%。目前为止,累计可以获益的肺癌患者不到50%。如果把小细胞肺癌、肺的鳞癌考虑进来,获益人群就更少了。

靶向治疗就像我们的改革开放,让一部分有特殊基因的人先活得长了起来!

2015~ 免疫治疗时代,让所有的病人活得长、活得好,把肺癌变成慢性病

免疫治疗进入肺癌的时间不长,但是已经令全球的医生和患者欢欣鼓舞!因为这也是一个0到1的改变。2017AACR和本次WCLC上关于PD-1/L1的长期数据的结果,让大家看到免疫治疗给肺癌患者带来长期生存的希望!



免疫治疗的一些研究结果

Checkmate-017、Checkmate-057、KEYNOTE-010、OAK研究、KEYNOTE 024研究,PACFIC研究等等一类系列的研究让医生者患者再次欢欣鼓舞!

免疫治疗可以给肺癌治疗带来又一个新时代吗??

目前看来,免疫治疗还需要解决几个关键的问题:

第一、免疫治疗的精准人群是什么?也就是如何把对免疫治疗有效的病人挑选出来的问题。到目前为止,我们还没有发现特别好的biomarker,TBM是一个潜在的标志物,但是可能精确度还不够。



如何进一步提高免疫治疗的疗效?

第二、如何进一步提高免疫治疗的疗效!联合治疗是解决问题的方法吗?联合化疗?联合放疗?联合手术?联合靶向?联合免疫?……很多的研究正在进行,目前还不能下定论。

一个新时代的到来,总是以新机制和新药物为标志,一个新时代也必然会带来患者治疗效果的突飞猛进!肺癌的药物治疗已经走过30多年的历史,人们对肺癌治疗效果的期待也是越来越高!目前的免疫治疗药物是否可以满足人们的需求,让我们拭目以待!


本庶右(Tasuku Honjo)教授对未来的预测

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    2017-10-24 chunjianf

    学习了.谢谢分享!

    0

  3. 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createdName=chunjianf, createdTime=Tue Oct 24 06:34:30 CST 2017, time=2017-10-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=255234, encodeId=a19d25523439, content=学习吧.认真看, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo61WAV0ROeLAoicPxPKoKaogwLWLL8STv86qplbdOibN2YR4KxkJicqNectCXGR8gPJhGLc7yYLSdnpx4kaVXndTfu/0, createdBy=a6962042337, createdName=1391e9f2a7m, createdTime=Mon Oct 23 06:27:07 CST 2017, time=2017-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1412351, encodeId=ef461412351b8, content=<a href='/topic/show?id=de711863ed3' target=_blank style='color:#2F92EE;'>#WCLC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18637, encryptionId=de711863ed3, topicName=WCLC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=91252863770, createdName=木头人514, createdTime=Sun Oct 22 14:27:00 CST 2017, time=2017-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1582626, encodeId=f4b615826265b, content=<a href='/topic/show?id=36455839121' target=_blank style='color:#2F92EE;'>#新时代#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58391, encryptionId=36455839121, topicName=新时代)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=30bd35, createdName=一叶知秋, createdTime=Sun Oct 22 14:27:00 CST 2017, time=2017-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=255099, encodeId=7d1c255099e7, content=谢谢分享.很不错的总结!, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, 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likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/be4YlKNv3rT6se8HUMWmAyS3eywXjKkf3TaeJkKrgAdTM1l1WesYwgkw2VAOVEWicdb6rCiaRbttqjb9ozpjCkGQ/0, createdBy=2d322139779, createdName=欧阳星月dora, createdTime=Sat Oct 21 09:43:22 CST 2017, time=2017-10-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=254768, encodeId=5121254e68fb, content=谢谢分享.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Sat Oct 21 06:58:43 CST 2017, time=2017-10-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=254737, encodeId=7d3f254e3722, content=新知识.新方法.新时代, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Sat Oct 21 06:25:38 CST 2017, time=2017-10-21, status=1, ipAttribution=)]
    2017-10-23 1391e9f2a7m

    学习吧.认真看

    0

  4. 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content=新知识.新方法.新时代, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Sat Oct 21 06:25:38 CST 2017, time=2017-10-21, status=1, ipAttribution=)]
    2017-10-22 木头人514
  5. 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  6. 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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTIxvMP6OXzUiaGH5MkDQlW0hczROZxec1gZjfZ52EtN6aG9t0uDZq2A5xmf9FWMa4tZib4qoYnledFg/132, createdBy=9d6c2167401, createdName=hanmeijinxiu, createdTime=Sun Oct 22 13:28:23 CST 2017, time=2017-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=255075, encodeId=6fc12550e559, content=提纲挈领 学习了!谢谢, beContent=null, objectType=article, channel=null, level=null, likeNumber=89, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20170803/IMG5982F7A3DBB3C1061.jpg, createdBy=0ba51605600, createdName=Jianghuiqin, createdTime=Sun Oct 22 10:25:31 CST 2017, time=2017-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=254842, encodeId=ce1e25484237, content=已经学习.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/be4YlKNv3rT6se8HUMWmAyS3eywXjKkf3TaeJkKrgAdTM1l1WesYwgkw2VAOVEWicdb6rCiaRbttqjb9ozpjCkGQ/0, createdBy=2d322139779, createdName=欧阳星月dora, createdTime=Sat Oct 21 09:43:22 CST 2017, time=2017-10-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=254768, encodeId=5121254e68fb, content=谢谢分享.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Sat Oct 21 06:58:43 CST 2017, time=2017-10-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=254737, encodeId=7d3f254e3722, content=新知识.新方法.新时代, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Sat Oct 21 06:25:38 CST 2017, time=2017-10-21, status=1, ipAttribution=)]
    2017-10-22 hanmeijinxiu

    谢谢分享.很不错的总结!

    0

  7. 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likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/be4YlKNv3rT6se8HUMWmAyS3eywXjKkf3TaeJkKrgAdTM1l1WesYwgkw2VAOVEWicdb6rCiaRbttqjb9ozpjCkGQ/0, createdBy=2d322139779, createdName=欧阳星月dora, createdTime=Sat Oct 21 09:43:22 CST 2017, time=2017-10-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=254768, encodeId=5121254e68fb, content=谢谢分享.学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Sat Oct 21 06:58:43 CST 2017, time=2017-10-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=254737, encodeId=7d3f254e3722, content=新知识.新方法.新时代, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Sat Oct 21 06:25:38 CST 2017, time=2017-10-21, status=1, ipAttribution=)]
    2017-10-22 Jianghuiqin

    提纲挈领 学习了!谢谢

    0

  8. 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content=新知识.新方法.新时代, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Sat Oct 21 06:25:38 CST 2017, time=2017-10-21, status=1, ipAttribution=)]
    2017-10-21 欧阳星月dora

    已经学习.谢谢分享

    0

  9. 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    2017-10-21 明月清辉

    谢谢分享.学习了

    0

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    2017-10-21 yjs木玉

    新知识.新方法.新时代

    0

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