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JAMA Oncology：高风险肾细胞癌肾切除术后Girentuximab辅助治疗

2017-07-11 MedSci MedSci原创

肾细胞癌肾切除术Girentuximab
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Girentuximab是一种结合了碳酸酐酶Ⅸ的嵌合式单克隆抗体，碳酸酐酶Ⅸ是肾透明细胞癌（ccRCC）细胞表明广泛表达的糖蛋白。在Ⅱ期研究中已验证了其安全性和活性，从而推进了其作为高风险ccRCC辅助治疗药物的进一步研究。JAMA Oncology近期发表了一篇文章，评估了Girentuximab辅助治疗对局部完全切除的高风险ccRCC患者无病生存（DFS）以及总生存（OS）的影响。

Girentuximab是一种结合了碳酸酐酶Ⅸ的嵌合式单克隆抗体，碳酸酐酶Ⅸ是肾透明细胞癌（ccRCC）细胞表明广泛表达的糖蛋白。在Ⅱ期研究中已验证了其安全性和活性，从而推进了其作为高风险ccRCC辅助治疗药物的进一步研究。JAMA Oncology近期发表了一篇文章，评估了Girentuximab辅助治疗对局部完全切除的高风险ccRCC患者无病生存（DFS）以及总生存（OS）的影响。

ARISER是一项随机双盲的Ⅲ期临床试验，研究时间为2004年6月到2013年4月2日。共有北美、南美以及欧洲15个国家142个中心参与。确诊为ccRCC的患者接受部分或根治性肾切除术。患者通过计算机随机分为试验组和安慰剂对照组。试验组在第1周接受50mgGirentuximab治疗后每周静脉注射Girentuximab 20mg（2-24周）。研究的主要终点是DFS和OS，次要终点包括安全性，不良事件发生率及程度。研究共纳入864例患者。与安慰剂组相比，接受Girentuximab治疗的患者DFS或OS并无显着改善。Girentuximab组平均DFS为71.4个月，安慰剂组未达到。185例患者出现药物相关不良反应（21.6%）。72例患者出现严重不良反应（8.4%）。接受安慰剂的患者出现1例药物相关严重不良反应。

文章最后认为，Girentuximab作为高风险ccRCC患者的辅助治疗方式无临床获益。患者表现出的长DFS和OS是ccRCC辅助治疗药物开发的挑战。

原始出处：
Karim Chamie,Nicholas M.Donin,et al.Adjuvant Weekly Girentuximab Following Nephrectomy for High-Risk Renal Cell Carcinoma.JAMA Oncology.July 2017 doi:10.1001/jamaoncol.2016.4419

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    2018-01-06 minlingfeng

    #Oncol#

    0

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    2017-07-31 snf701207

    #mAb#

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    2018-06-06 circumcision

    #Oncology#

    0

  4. 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content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4Nd44v3xHnnictn9UpctwtH62EPQ59TMdI9lnqHMgQ16nH7GmGCfpzicsHgjibYVk6vwSpXrC86gMibRkoaIzf5HwSz7/0, createdBy=78cc1691107, createdName=龙胆草, createdTime=Thu Jul 13 06:41:56 CST 2017, time=2017-07-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=221438, encodeId=433422143891, content=谢谢分享，学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=1, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Wed Jul 12 15:12:02 CST 2017, time=2017-07-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=221305, encodeId=7fb5221305f1, content=希望能彻底治疗, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160718/IMG578C993D395567540.jpg, createdBy=59b81918946, createdName=flysky120, createdTime=Wed Jul 12 07:20:13 CST 2017, time=2017-07-12, status=1, ipAttribution=)]
    2018-04-02 doctorzheng

    #切除术#

    0

  5. 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content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4Nd44v3xHnnictn9UpctwtH62EPQ59TMdI9lnqHMgQ16nH7GmGCfpzicsHgjibYVk6vwSpXrC86gMibRkoaIzf5HwSz7/0, createdBy=78cc1691107, createdName=龙胆草, createdTime=Thu Jul 13 06:41:56 CST 2017, time=2017-07-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=221438, encodeId=433422143891, content=谢谢分享，学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=1, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Wed Jul 12 15:12:02 CST 2017, time=2017-07-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=221305, encodeId=7fb5221305f1, content=希望能彻底治疗, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160718/IMG578C993D395567540.jpg, createdBy=59b81918946, createdName=flysky120, createdTime=Wed Jul 12 07:20:13 CST 2017, time=2017-07-12, status=1, ipAttribution=)]
    2017-11-02 zlawrance

    #高风险#

    0

  6. 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content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4Nd44v3xHnnictn9UpctwtH62EPQ59TMdI9lnqHMgQ16nH7GmGCfpzicsHgjibYVk6vwSpXrC86gMibRkoaIzf5HwSz7/0, createdBy=78cc1691107, createdName=龙胆草, createdTime=Thu Jul 13 06:41:56 CST 2017, time=2017-07-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=221438, encodeId=433422143891, content=谢谢分享，学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=1, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Wed Jul 12 15:12:02 CST 2017, time=2017-07-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=221305, encodeId=7fb5221305f1, content=希望能彻底治疗, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160718/IMG578C993D395567540.jpg, createdBy=59b81918946, createdName=flysky120, createdTime=Wed Jul 12 07:20:13 CST 2017, time=2017-07-12, status=1, ipAttribution=)]
    2017-10-03 qingting

    #细胞癌#

    0

  7. 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content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=109, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4Nd44v3xHnnictn9UpctwtH62EPQ59TMdI9lnqHMgQ16nH7GmGCfpzicsHgjibYVk6vwSpXrC86gMibRkoaIzf5HwSz7/0, createdBy=78cc1691107, createdName=龙胆草, createdTime=Thu Jul 13 06:41:56 CST 2017, time=2017-07-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=221438, encodeId=433422143891, content=谢谢分享，学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=1, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Wed Jul 12 15:12:02 CST 2017, time=2017-07-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=221305, encodeId=7fb5221305f1, content=希望能彻底治疗, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160718/IMG578C993D395567540.jpg, createdBy=59b81918946, createdName=flysky120, createdTime=Wed Jul 12 07:20:13 CST 2017, time=2017-07-12, status=1, ipAttribution=)]
    2017-08-25 gaoxiaoe

    #肾切除术#

    0

  8. 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=221305, encodeId=7fb5221305f1, content=希望能彻底治疗, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160718/IMG578C993D395567540.jpg, createdBy=59b81918946, createdName=flysky120, createdTime=Wed Jul 12 07:20:13 CST 2017, time=2017-07-12, status=1, ipAttribution=)]
    2017-07-13 龙胆草

    学习谢谢分享

    0

  9. 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=221305, encodeId=7fb5221305f1, content=希望能彻底治疗, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160718/IMG578C993D395567540.jpg, createdBy=59b81918946, createdName=flysky120, createdTime=Wed Jul 12 07:20:13 CST 2017, time=2017-07-12, status=1, ipAttribution=)]
    2017-07-12 清风拂面

    谢谢分享，学习了

    0

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    2017-07-12 flysky120

    希望能彻底治疗

    0

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日前，罗氏集团公司基因泰克宣布了一项2期临床试验的最新数据。在这项试验中，TECENTRIQ®（atezolizumab）与Avastin®（bevacizumab）的联合疗法显著延长了初治晚期或转移性肾细胞患者的无进展生存期。此项免疫组合疗法也有望成为治疗肾细胞癌的全新一线疗法。

诺华药物依维莫司通过英国重新审查，作为二线药物治疗肾细胞癌

英国国家健康和护理研究所废除了此前关于依维莫司的规定，将推荐该药物作为治疗肾肿瘤的常规药物。此前由于英国启动NICE2011方案重新评估所有癌症药物基金支持的治疗方案，依维莫司只有在通过该方案审查后才可以使用。 而现在由于诺华提供了新的证据，NICE批准将该药物作为晚期肾细胞癌（RCC）的二线治疗药物。NICE卫生技术评估中心主任Carole Longson教授说道：“肾细胞癌是一种相对罕见的癌

Nat commun：MYC的激活与Vhl和Ink4a/Arf 功能的丢失可以诱导透明细胞肾细胞癌

肾癌是一种常见的并且具有侵入性的恶性肿瘤，并且该病的组织病理学并没有被人们完全理解。大多肾癌对细胞毒药物治疗具有抗性。最近，有研究人员利用两个肾癌小鼠模型来表述在人类乳头状肾细胞癌（pRCC）和透明细胞肾细胞癌（ccRCC）， 这两种是最为常见的肾细胞癌亚型。研究发现，MYC激活导致高度渗透的乳头状肾细胞癌肿瘤（MYC），然而，当MYC激活与Vhl 和 Cdkn2a(Ink4a/Arf) 缺失 (

Nat Commun：VHL缺陷通过下调ALDH2增强透明细胞肾细胞癌的蒽环霉素敏感性

肾细胞癌是肾肿瘤中最常见的一种类型。众所周知，RCC对常规化学治疗有抵抗性，大多数病人在化学治疗中饱受副作用之苦，肾肿瘤的药物治疗依然不甚理想。因而，目前急需鉴别针对RCC的潜在治疗靶点和化学药剂。

JCO：晚期乳头状肾细胞癌患者使用savolitinib的生物标志物（II期试验）

晚期乳头状肾细胞癌（PRCC）的治疗选择是有限的。其可能涉及的MET通路的激活，例如，通过基因扩增或基因突变。Savolitinib（AZD6094, HMPL-504,沃利替尼）是一种高选择性MET酪氨酸激酶抑制剂。近期发表在JCO上的一项研究中，研究人员报告了一个单臂、多中心、II期研究，该研究根据MET状态评估了在PRCC患者中Savolitinib的安全性和疗效。被诊断为局部晚期或转移性乳

JCO：Nivolumab联合Ipilimumab治疗转移性肾细胞癌

免疫检查点抑制剂联合治疗与单药治疗相比具有更强的抗肿瘤活性。Ⅰ期Checkmate 016研究主要评估Nivolumab联合Ipilimumab以及Nivolumab加一种酪氨酸激酶抑制剂治疗转移性肾细胞癌（mRCC）的有效性及安全性。JCO近期发表了一篇文章，报道了Nivolumab联合Ipilimumab组的安全性及有效性结果。

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