复发低级别浆液性卵巢癌:KRAS突变可预测MEK抑制剂Binimetinib获益

2021-01-23 太后殿下 张师前 张师前公众号

美国纪念斯隆凯特琳癌症中心Grisham等报告的对MILO研究的析因分析显示,KRAS突变可预测MEK抑制剂Binimetinib获益,KRAS突变患者有近7个月无进展生存获益。(2020 SGO年会

美国纪念斯隆凯特琳癌症中心Grisham等报告的对MILO研究的析因分析显示,KRAS突变可预测MEK抑制剂Binimetinib获益,KRAS突变患者有近7个月无进展生存获益。(2020 SGO年会摘要号41)

接受 MEK 抑制剂治疗的患者中,KRAS突变患者无进展生存显著长于野生型患者(17.7 个月 vs.10.8个月,P=0.006);化疗组中,KRAS突变患者中位PFS为14.6个月,野生型患者为11.5个月,不过差异不显著(P=0.502)。更新的研究主要终点的分析显示,所有患者人群中,Binimetinib未显示有PFS获益,Binimetinib 组和医生选择化疗组中位PFS分别为10.4个月和11.5个月(HR=1.15,95%CI 0.76~1.74)。

两组患者均有24%的患者有客观缓解,MEK抑制剂组和化疗组分别有3%和1%的患者完全缓解,60%和54%的患者疾病稳定。

有评论者表示,该研究中化疗组的获益超乎预期。联想到ESMO年会上公布的Trametinib可带来优于标准化疗的PFS获益,有PFS改善是否就意味着有望成为新的标准治疗,在治疗选择较少的少见类型肿瘤领域可能是这样的,因为这对患者来讲意义重大。 

有KRAS突变的患者的确获益更显著,可以告知患者若他们有KRAS或NRAS突变或BRAF突变,他们更有可能从Binimetinib治疗中获益。目前所有复发低级别浆液性卵巢癌患者都可考虑Binimetinib治疗,没有KRAS突变不等于不能接受MEK抑制剂治疗。KRAS突变可能可用于风险受益决策,有KRAS突变提示获益权重较毒性反应要更重一些。

MILO研究中,几乎所有患者均发生不良反应,试验组腹泻、皮疹、外周水肿、肌酸升高等发生率高于化疗组,3~4 级不良反应发生率也较高(76% vs. 44%),因不良反应导致的停药率也较高(20% vs. 11%)。

MILO 研究于2013年开展,从17个国家入组341例患者,2 : 1比例随机分组分别接受Binimetinib(340 mg bid) 或医生选择的化疗,所有患者此前接受过手术,1/3接受过激素治疗。Binimetinib组和化疗组中位年龄分别为54岁和50岁,KRAS突变率分别为32%和34%,KRAS突变状态与Binimetinib疗效相关,但与化疗疗效无关。Binimetinib 目前获批联合Encorafenib用于治疗BRAF V600E或V600K突变不可切除或转移性黑色素瘤,还在其他多种类型肿瘤中开展临床试验。

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    2021-08-23 一闲
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    2021-09-29 jklm09
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  4. [GetPortalCommentsPageByObjectIdResponse(id=1896805, encodeId=01b618968054a, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Mon Aug 23 14:08:31 CST 2021, time=2021-08-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1852589, encodeId=bc391852589d8, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed Sep 29 05:08:31 CST 2021, time=2021-09-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1665206, encodeId=08de1665206ad, content=<a href='/topic/show?id=565f341e8a' target=_blank style='color:#2F92EE;'>#binimetinib#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3417, encryptionId=565f341e8a, topicName=binimetinib)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7f1a25912110, createdName=12498e0fm86暂无昵称, createdTime=Wed Nov 10 01:08:31 CST 2021, time=2021-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1943921, encodeId=068e194392173, content=<a href='/topic/show?id=d2af1152597' target=_blank style='color:#2F92EE;'>#MEK#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11525, encryptionId=d2af1152597, topicName=MEK)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5b0e350, createdName=naiwu77, createdTime=Tue May 04 07:08:31 CST 2021, time=2021-05-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1332875, encodeId=4e5b13328e5b0, content=<a href='/topic/show?id=e070105e2bb' target=_blank style='color:#2F92EE;'>#KRAS突变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10572, encryptionId=e070105e2bb, topicName=KRAS突变)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/17F844FBE270B8196CB4C53EC9493C57/100, createdBy=9d712500079, createdName=ms5906905816781247, createdTime=Sun Jan 24 04:08:31 CST 2021, time=2021-01-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1369030, encodeId=7214136903072, content=<a href='/topic/show?id=13cb1056e20' target=_blank style='color:#2F92EE;'>#KRAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10567, encryptionId=13cb1056e20, topicName=KRAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8217292, createdName=yinhl1978, createdTime=Sun Jan 24 04:08:31 CST 2021, time=2021-01-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512737, encodeId=73851512e37dd, content=<a href='/topic/show?id=c3e91152873' target=_blank style='color:#2F92EE;'>#MEK抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11528, encryptionId=c3e91152873, topicName=MEK抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=318b10497059, createdName=ms2186806800017884, createdTime=Sun Jan 24 04:08:31 CST 2021, time=2021-01-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1585332, encodeId=63df15853322a, content=<a href='/topic/show?id=792b15145a6' target=_blank style='color:#2F92EE;'>#RAS突变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15145, encryptionId=792b15145a6, topicName=RAS突变)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6f2c17156536, createdName=bioon7, createdTime=Sun Jan 24 04:08:31 CST 2021, time=2021-01-24, status=1, ipAttribution=)]
    2021-05-04 naiwu77
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    2021-01-24 yinhl1978
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    2021-01-24 bioon7

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