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JCO:Tipifarnib对复发和/或转移性头颈鳞癌疗效显著

2021-03-24 MedSci原创 MedSci原创

复发和/或转移性(R/M)头颈部鳞状细胞癌(HNSCC)患者中,原癌基因 HRAS (mHRAS)突变发生率为4%-8% 。Tipifarnib是一种法尼基转移酶抑制剂,可以扰乱 HRAS 功能。

复发和/或转移性(R/M)头颈部鳞状细胞癌(HNSCC)患者中,原癌基因 HRAS (mHRAS)突变发生率为4%-8% 。Tipifarnib是一种法尼基转移酶抑制剂,可以扰乱 HRAS 功能。该实验评估了Tipifarnib治疗R/M mHRAS-HNSCC患者的疗效。

2021年3月22日,Journal of Clinical Oncology在线发表了一项研究,结果显示Tipifarnib对携带HRAS突变的R/M mHRAS-HNSCC患者疗效显著。

HNSCC每年占全球新增癌症病例中的五十多万例,主要与吸烟和酒精暴露或感染人类乳头瘤病毒(HPV)有关。尽管最近靶向治疗被纳入标准治疗,但R/M HNSCC 患者的预后仍然很差,估计总生存期的中位数为13-15个月。自10多年前批准西妥昔单抗以来,靶向药物的开发一直受到药物可靶向的标志物数量有限和药物难治性疾病侵袭性的困扰。该研究纳入了22例R/M HNSCC患者,这些患者mHRAS等位基因突变频率(VAF)≥20%(高VAF)。研究的主要终点为客观缓解率(ORR),次要终点包括安全性和耐受性。受试者在28天治疗周期的第1-7天和第15-21天口服Tipifarnib600或900mg,每日两次。
结果显示,在22名接受VAF治疗的患者中,有20例患者最终可进行评价疗效,如图所示,高VAF-HNSCC患者的ORR为55%。Tipifarnib治疗的中位无进展生存期(PFS)为5.6个月,中位总生存期(OS)为15.4个月。最常见的治疗相关不良事件为贫血(37%)和淋巴细胞减少(13%)。

服用Tipifarnib后,PFS中位数提高到5.6个月,与治疗前的3.6个月比较,差异有统计学意义,中位OS为15.4个月。

本研究描述了Tipifarnib对R/M HNSCC患者的抗肿瘤活性的作用,ORR为前所未有的55%,这一发现是极其令人鼓舞的。西妥昔单抗,纳武单抗等靶向药物的历史有效率约15%,而Tipifarnib反应迅速,持续时间长,本实验患者中其中7例反应时间超过6个月。重要的是,这些患者在之前治疗中并没有出现类似的反应。

该实验另一个引人注目的结果是,可评估的高mHRAS VAF治愈患者的临床受益为100%,这是mHRAS作为肿瘤驱动因素的作用以及FTIs植入治疗肿瘤的能力提供了额外的证据。

参考文献:

Ho AL, Brana I, Haddad R, et al. Tipifarnib in Head and Neck Squamous Cell Carcinoma With HRAS Mutations. J Clin Oncol. 2021 Mar 22:JCO2002903. doi: 10.1200/JCO.20.02903. Epub ahead of print. PMID: 33750196.

https://ascopubs.org/doi/10.1200/JCO.20.02903?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

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    2021-03-26 gongliu
  6. [GetPortalCommentsPageByObjectIdResponse(id=1891637, encodeId=d415189163e61, content=<a href='/topic/show?id=25b0102e2df' target=_blank style='color:#2F92EE;'>#JCO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10272, encryptionId=25b0102e2df, topicName=JCO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6da1120, createdName=lidong40, createdTime=Sat Apr 10 02:53:49 CST 2021, time=2021-04-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1386734, encodeId=fa5f1386e34f5, content=<a href='/topic/show?id=f08293399f9' target=_blank style='color:#2F92EE;'>#转移性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93399, encryptionId=f08293399f9, topicName=转移性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1ac22500003, createdName=1249842em09(暂无昵称), createdTime=Fri Mar 26 13:53:49 CST 2021, time=2021-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1484681, encodeId=d66b1484681ec, content=<a href='/topic/show?id=3502102944e7' target=_blank style='color:#2F92EE;'>#鳞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102944, encryptionId=3502102944e7, topicName=鳞癌)], attachment=null, authenticateStatus=null, createdAvatar=Bioon/avatar/20171006/a73877485ccdf6add82293e671bebe21.jpg, createdBy=745a7977375, createdName=1696533704_45270456, createdTime=Fri Mar 26 13:53:49 CST 2021, time=2021-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1545920, encodeId=6cfd1545920c2, content=<a href='/topic/show?id=e3ed44439b1' target=_blank style='color:#2F92EE;'>#头颈鳞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44439, encryptionId=e3ed44439b1, topicName=头颈鳞癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e7bf13828981, createdName=ms5106640509429053, createdTime=Fri Mar 26 13:53:49 CST 2021, time=2021-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1624587, encodeId=ef87162458ef5, content=<a href='/topic/show?id=3f2d2e7087' target=_blank style='color:#2F92EE;'>#ARNI#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2770, encryptionId=3f2d2e7087, topicName=ARNI)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f41c20676233, createdName=gongliu, createdTime=Fri Mar 26 13:53:49 CST 2021, time=2021-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=950988, encodeId=099595098804, content=鳞癌疗效显著, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210110/e6124a4b19bc40ce8afaae096d21126b/dd778ac260c9416eb87e7d08139507f5.jpg, createdBy=4d2f5079605, createdName=科研科研科研, createdTime=Thu Mar 25 12:36:40 CST 2021, time=2021-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=950930, encodeId=e3f0950930f1, content=赞👍, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJibu7hwJqpmHiaJgLLmJmcwp0WDTxWI3vqPBO1Mloq21VBOPqziapyibYatvd2QWHWicolL1vbVZHgpRQ/132, createdBy=d16a2107341, createdName=JZ Yang, createdTime=Thu Mar 25 09:34:45 CST 2021, time=2021-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1032851, encodeId=50301032851b5, content=谢谢梅斯提供这么好的信息,学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Thu Mar 25 01:53:49 CST 2021, time=2021-03-25, status=1, ipAttribution=)]
    2021-03-25 科研科研科研

    鳞癌疗效显著

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1891637, encodeId=d415189163e61, content=<a href='/topic/show?id=25b0102e2df' target=_blank style='color:#2F92EE;'>#JCO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10272, encryptionId=25b0102e2df, topicName=JCO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6da1120, createdName=lidong40, createdTime=Sat Apr 10 02:53:49 CST 2021, time=2021-04-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1386734, encodeId=fa5f1386e34f5, content=<a href='/topic/show?id=f08293399f9' target=_blank style='color:#2F92EE;'>#转移性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93399, encryptionId=f08293399f9, topicName=转移性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1ac22500003, createdName=1249842em09(暂无昵称), createdTime=Fri Mar 26 13:53:49 CST 2021, time=2021-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1484681, encodeId=d66b1484681ec, content=<a href='/topic/show?id=3502102944e7' target=_blank style='color:#2F92EE;'>#鳞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102944, encryptionId=3502102944e7, topicName=鳞癌)], attachment=null, authenticateStatus=null, createdAvatar=Bioon/avatar/20171006/a73877485ccdf6add82293e671bebe21.jpg, createdBy=745a7977375, createdName=1696533704_45270456, createdTime=Fri Mar 26 13:53:49 CST 2021, time=2021-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1545920, encodeId=6cfd1545920c2, content=<a href='/topic/show?id=e3ed44439b1' target=_blank style='color:#2F92EE;'>#头颈鳞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44439, encryptionId=e3ed44439b1, topicName=头颈鳞癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e7bf13828981, createdName=ms5106640509429053, createdTime=Fri Mar 26 13:53:49 CST 2021, time=2021-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1624587, encodeId=ef87162458ef5, content=<a href='/topic/show?id=3f2d2e7087' target=_blank style='color:#2F92EE;'>#ARNI#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2770, encryptionId=3f2d2e7087, topicName=ARNI)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f41c20676233, createdName=gongliu, createdTime=Fri Mar 26 13:53:49 CST 2021, time=2021-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=950988, encodeId=099595098804, content=鳞癌疗效显著, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210110/e6124a4b19bc40ce8afaae096d21126b/dd778ac260c9416eb87e7d08139507f5.jpg, createdBy=4d2f5079605, createdName=科研科研科研, createdTime=Thu Mar 25 12:36:40 CST 2021, time=2021-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=950930, encodeId=e3f0950930f1, content=赞👍, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJibu7hwJqpmHiaJgLLmJmcwp0WDTxWI3vqPBO1Mloq21VBOPqziapyibYatvd2QWHWicolL1vbVZHgpRQ/132, createdBy=d16a2107341, createdName=JZ Yang, createdTime=Thu Mar 25 09:34:45 CST 2021, time=2021-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1032851, encodeId=50301032851b5, content=谢谢梅斯提供这么好的信息,学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Thu Mar 25 01:53:49 CST 2021, time=2021-03-25, status=1, ipAttribution=)]
    2021-03-25 JZ Yang

    赞👍

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1891637, encodeId=d415189163e61, content=<a href='/topic/show?id=25b0102e2df' target=_blank style='color:#2F92EE;'>#JCO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10272, encryptionId=25b0102e2df, topicName=JCO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6da1120, createdName=lidong40, createdTime=Sat Apr 10 02:53:49 CST 2021, time=2021-04-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1386734, encodeId=fa5f1386e34f5, content=<a href='/topic/show?id=f08293399f9' target=_blank style='color:#2F92EE;'>#转移性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=93399, encryptionId=f08293399f9, topicName=转移性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1ac22500003, createdName=1249842em09(暂无昵称), createdTime=Fri Mar 26 13:53:49 CST 2021, time=2021-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1484681, encodeId=d66b1484681ec, content=<a href='/topic/show?id=3502102944e7' target=_blank style='color:#2F92EE;'>#鳞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102944, encryptionId=3502102944e7, topicName=鳞癌)], attachment=null, authenticateStatus=null, createdAvatar=Bioon/avatar/20171006/a73877485ccdf6add82293e671bebe21.jpg, createdBy=745a7977375, createdName=1696533704_45270456, createdTime=Fri Mar 26 13:53:49 CST 2021, time=2021-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1545920, encodeId=6cfd1545920c2, content=<a href='/topic/show?id=e3ed44439b1' target=_blank style='color:#2F92EE;'>#头颈鳞癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44439, encryptionId=e3ed44439b1, topicName=头颈鳞癌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e7bf13828981, createdName=ms5106640509429053, createdTime=Fri Mar 26 13:53:49 CST 2021, time=2021-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1624587, encodeId=ef87162458ef5, content=<a href='/topic/show?id=3f2d2e7087' target=_blank style='color:#2F92EE;'>#ARNI#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2770, encryptionId=3f2d2e7087, topicName=ARNI)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f41c20676233, createdName=gongliu, createdTime=Fri Mar 26 13:53:49 CST 2021, time=2021-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=950988, encodeId=099595098804, content=鳞癌疗效显著, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210110/e6124a4b19bc40ce8afaae096d21126b/dd778ac260c9416eb87e7d08139507f5.jpg, createdBy=4d2f5079605, createdName=科研科研科研, createdTime=Thu Mar 25 12:36:40 CST 2021, time=2021-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=950930, encodeId=e3f0950930f1, content=赞👍, beContent=null, objectType=article, channel=null, level=null, likeNumber=102, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJibu7hwJqpmHiaJgLLmJmcwp0WDTxWI3vqPBO1Mloq21VBOPqziapyibYatvd2QWHWicolL1vbVZHgpRQ/132, createdBy=d16a2107341, createdName=JZ Yang, createdTime=Thu Mar 25 09:34:45 CST 2021, time=2021-03-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1032851, encodeId=50301032851b5, content=谢谢梅斯提供这么好的信息,学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=内科新手, createdTime=Thu Mar 25 01:53:49 CST 2021, time=2021-03-25, status=1, ipAttribution=)]
    2021-03-25 内科新手

    谢谢梅斯提供这么好的信息,学到很多

    0

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