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今日ASCO要闻: 免疫疗法、精准医学、Claudin18.2

2016-06-06 佚名 美中药源

美中药源
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今天ASCO渐入佳境，免疫疗法和精准医学作为本届年会的两大主题贯穿几个主要进展。不出所料，检查点抑制剂及其组合是大家关注的重点。其中PD-1抑制剂进入肺癌一线治疗是重中之重，因为肺癌是世界死亡人数最高的恶性肿瘤。在Checkmate-012中，Opdivo/Yervoy组合产生43%总应答率，在高表达PD-L1(>50%)人群中高达92%的病人对这个组合应答。这一方面显示PD-L1作为一个生


今天ASCO渐入佳境，免疫疗法和精准医学作为本届年会的两大主题贯穿几个主要进展。

不出所料，检查点抑制剂及其组合是大家关注的重点。其中PD-1抑制剂进入肺癌一线治疗是重中之重，因为肺癌是世界死亡人数最高的恶性肿瘤。在Checkmate-012中，Opdivo/Yervoy组合产生43%总应答率，在高表达PD-L1(>50%)人群中高达92%的病人对这个组合应答。这一方面显示PD-L1作为一个生物标记至少在一定范围可以预测应答，更重要的是这显示以前被认为武功深不可测的晚期恶性肿瘤也并非铁板一块。不管肺癌有多少基因已经变异、变异多么不同，只要高表达PD-L1就会成为Opdivo/Yervoy组合的刀下鬼。这是一个非常令人欣慰的结果。

默沙东的Keytruda和各种化疗的组合也在一线肺癌产生50-70%的应答率，PFS比Opdivo/Yervoy组合甚至还要长1-2个月。罗氏的PD-L1抗体atezolizumab和MEK抑制剂cobimetinib组合在晚期结直肠癌产生20%应答，准备开始三期临床。Atezolizumab/Abraxane组合也在晚期三阴性乳腺癌产生38%应答率。但atezolizumab和另一个被寄予厚望的免疫激活剂OX40激动剂MOXR0916组合却令人失望，28位病人只有两例部分应答。检查点抑制剂以外免疫疗法乏善可点的表现令部分专家质疑现在免疫疗法是否存在泡沫。像任何运气为主的行业一样，意外发现之后的泡沫不可避免。

免疫疗法之外最大的一匹黑马当属Claudin18.2抗体IMAB362。在高表达Claudin18.2晚期胃癌患者中，IMAB362与化疗组合生存期是化疗的两倍（16.7对9个月），这是一个惊人的改进。Claudin家族蛋白发现不到20年，现在已知27个基因，但多数功能未知。Claudin18.2调控细胞膜性质，控制物质交换。借用钢铁料理的比喻，这类蛋白可能是未来几年抗癌领域竞争的一个关键食材。对于胃癌高发区的中国，这个靶点更加重要。

另一个重要突破是CD38抗体daratumumab，和标准疗法的组合在耐受/复发多发性骨髓瘤降低61%疾病进展或死亡风险，部分和完全应答率均翻倍。ADC药物Rova-T作为二线用药则在DLL3高表达小细胞肺癌患者产生39%应答率，一年生存率为32%。

这些靶向药物令药物使用更加精准。随着药物价格接近极限，患者对疗效和副作用要求更加严格。只有真正能获益的患者才能使用价格昂贵的新药，所以精确定义患者的肿瘤特征更加重要。液体活检虽然还不能代替组织活检，但一个大型研究显示现在的液体活检技术已经有相当的精确度。液体活检成本更低、操作更方便，是未来肿瘤诊断和检测进展的方向。

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    2016-06-19 quxin068

    #ASC#

    0

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    2016-09-11 hb2008ye

    #Claudin#

    0

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    2016-06-08 shijzhiewnjhch

    #精准#

    0

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    2016-06-07 老段

    精准医学

    0

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    2016-06-06 milkshark

    这个不错

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1938570, encodeId=f62f19385e0c6, content=<a href='/topic/show?id=1c292818fd' target=_blank style='color:#2F92EE;'>#ASC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2818, encryptionId=1c292818fd, topicName=ASC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=74808, createdName=quxin068, createdTime=Sun Jun 19 21:56:00 CST 2016, time=2016-06-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2048366, encodeId=c650204836672, content=<a href='/topic/show?id=e6364814ac' target=_blank style='color:#2F92EE;'>#Claudin#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4814, encryptionId=e6364814ac, topicName=Claudin)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Sun Sep 11 04:56:00 CST 2016, time=2016-09-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1403039, encodeId=da2f140303995, content=<a href='/topic/show?id=ebbde6353be' target=_blank style='color:#2F92EE;'>#精准#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76353, encryptionId=ebbde6353be, topicName=精准)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83epQX9hfEIBiaPg0e9KvLYVBCSGYydH6K6OQxBh3RaOC0TYP9HYy2v0XdHib1LFnZNU5Siak0P8oh8Aqw/132, createdBy=acd92440184, createdName=shijzhiewnjhch, createdTime=Wed Jun 08 03:56:00 CST 2016, time=2016-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=88868, encodeId=2bbb88868c8, content=精准医学, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2d331664955, createdName=老段, createdTime=Tue Jun 07 06:27:00 CST 2016, time=2016-06-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=88825, encodeId=296a8882597, content=这个不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7cde98330, createdName=milkshark, createdTime=Mon Jun 06 13:35:00 CST 2016, time=2016-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=88826, encodeId=e83b8882659, content=值得研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7cde98330, createdName=milkshark, createdTime=Mon Jun 06 13:35:00 CST 2016, time=2016-06-06, status=1, ipAttribution=)]
    2016-06-06 milkshark

    值得研究

    0