JCO:鲁卡帕利可有效治疗携带BRCA1/2或PALB2致病性突变的晚期胰腺癌

2021-05-12 Nebula MedSci原创

可能有更多的癌症患者可从PARPi治疗中获益,不局限于gBRCA1/2致病性突变的携带者

PARP抑制剂(PARPi)奥拉帕利(Olaparib)已获批用作携带BRCA1或BRCA2基因胚系致病性突变(PV)的晚期胰腺癌(PC)的维持疗法。

这是一项由调查员发起的单臂的2期临床试验,旨在评估另一种PARPi鲁卡帕利(rucaparib)作为维持疗法用于携带BRCA1、BRCA2或PALB2基因体系或胚系致病性突变的晚期胰腺癌的作用

受试患者招募条件:晚期胰腺癌,携带胚系(g)或体系(s)BRCA1、BRCA2或PALB2基因致病性突变,至少接受以铂类为基础的化疗治疗16周且无铂耐药迹象。停用化疗,予以鲁卡帕利 600 mg·2次/日口服,直到病情进展。主要终点是6个月时的无进展生存期(RFS)率(PFS6)。次要终点包括安全性、ORR、疾病控制率、缓解持续时间和总生存期。

共招募了46位患者,其中42位可评估(27位携带gBRCA2、7位携带gBRCA1、6位携带gPALB2、2位携带sBRCA2)。

整体队列的PFS和OS

PFS6为59.5%(95%CI 44.6-74.4),中位PFS为13.1个月(95%CI 4.4-21.8),中位总生存期为23.5个月(95%CI 20-27)。

36位可测量疾病的患者的最佳缓解情况

12个月时的PFS为54.8%。36位可测量疾病的患者的ORR为41.7%(3位完全缓解,12位部分缓解,95%CI 25.5-59.2),疾病控制率位66.7%(95%CI 49.0-81.4)。中位缓解持续时间为17.3个月(95%CI 8.8-25.8)。

携带不同突变的患者的PFS(A图)和OS(B图)

缓解发生于携带gBRCA2(41%,11/27)、gPALB2(50%, 3/6)和sBRCA2(50%,1/2)的患者。无新的安全性问题。

综上,鲁卡帕利维持疗法用于携带BRCA1、BRCA2或PALB2基因致病性突变的铂敏感的晚期胰腺癌患者的疗效良好,安全性佳。在携带gPALB2和SBRCA2基因致病性突变的晚期胰腺癌患者的有效性结果提示,可能有更多的癌症患者可从PARPi治疗中获益,不局限于gBRCA1/2致病性突变的携带者

原始出处:

Kim A. Reiss, et al. Phase II Study of Maintenance Rucaparib in Patients With Platinum-Sensitive Advanced Pancreatic Cancer and a Pathogenic Germline or Somatic Variant in BRCA1, BRCA2, or PALB2. Journal of Clinical Oncology. May 10, 2021. https://doi.org/10.1200/JCO.21.00003

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    2021-07-29 lidong40
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    2021-06-06 cnxcy
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  4. [GetPortalCommentsPageByObjectIdResponse(id=1891656, encodeId=36a9189165635, content=<a href='/topic/show?id=25b0102e2df' target=_blank style='color:#2F92EE;'>#JCO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10272, encryptionId=25b0102e2df, topicName=JCO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6da1120, createdName=lidong40, createdTime=Thu Jul 29 23:27:38 CST 2021, time=2021-07-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1718864, encodeId=cf1c1e18864c0, content=<a href='/topic/show?id=d3e9864e750' target=_blank style='color:#2F92EE;'>#致病性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86477, encryptionId=d3e9864e750, topicName=致病性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d36132650190, createdName=cnxcy, createdTime=Sun Jun 06 12:27:38 CST 2021, time=2021-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1389583, encodeId=9c2c138958348, content=<a href='/topic/show?id=82a95988106' target=_blank style='color:#2F92EE;'>#晚期胰腺癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=59881, encryptionId=82a95988106, topicName=晚期胰腺癌)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/2898B09F0DA89357D0D54A725E611AC7/100, createdBy=fdd32500040, createdName=ms7899726347904398, createdTime=Fri May 14 08:27:38 CST 2021, time=2021-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1423319, encodeId=f3851423319b5, content=<a href='/topic/show?id=504c368e51' target=_blank style='color:#2F92EE;'>#BRCA1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, 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target=_blank style='color:#2F92EE;'>#BRCA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3684, encryptionId=63cc368459, topicName=BRCA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=智智灵药, createdTime=Fri May 14 08:27:38 CST 2021, time=2021-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1619605, encodeId=4c3c161960529, content=<a href='/topic/show?id=8dd46061824' target=_blank style='color:#2F92EE;'>#有效治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=60618, encryptionId=8dd46061824, topicName=有效治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Fri May 14 08:27:38 CST 2021, time=2021-05-14, status=1, ipAttribution=), 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encryptionId=23e3454e353, topicName=学习)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9e3a5478833, createdName=ms5000000790714074, createdTime=Wed May 12 19:47:21 CST 2021, time=2021-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=964964, encodeId=6f8596496403, content=学习了!!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210606/3360b859ba944059aaffe8a1847ab57b/e91f325d086a40b2b9805211738111d1.jpg, createdBy=b3982392941, createdName=牟德武, createdTime=Wed May 12 17:32:01 CST 2021, time=2021-05-12, status=1, ipAttribution=)]
  5. 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target=_blank style='color:#2F92EE;'>#BRCA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3684, encryptionId=63cc368459, topicName=BRCA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=智智灵药, createdTime=Fri May 14 08:27:38 CST 2021, time=2021-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1619605, encodeId=4c3c161960529, content=<a href='/topic/show?id=8dd46061824' target=_blank style='color:#2F92EE;'>#有效治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=60618, encryptionId=8dd46061824, topicName=有效治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Fri May 14 08:27:38 CST 2021, time=2021-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1621435, encodeId=36ca162143596, content=<a href='/topic/show?id=8f7d1368929' target=_blank style='color:#2F92EE;'>#PALB2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13689, encryptionId=8f7d1368929, topicName=PALB2)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Fri May 14 08:27:38 CST 2021, time=2021-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=964986, encodeId=01ff96498684, content=受益匪浅<a href='/topic/show?id=23e3454e353' target=_blank style='color:#2F92EE;'>#学习#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=45473, encryptionId=23e3454e353, topicName=学习)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9e3a5478833, createdName=ms5000000790714074, createdTime=Wed May 12 19:47:21 CST 2021, time=2021-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=964964, encodeId=6f8596496403, content=学习了!!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210606/3360b859ba944059aaffe8a1847ab57b/e91f325d086a40b2b9805211738111d1.jpg, createdBy=b3982392941, createdName=牟德武, createdTime=Wed May 12 17:32:01 CST 2021, time=2021-05-12, status=1, ipAttribution=)]
    2021-05-14 fangcong
  6. 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target=_blank style='color:#2F92EE;'>#BRCA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3684, encryptionId=63cc368459, topicName=BRCA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=智智灵药, createdTime=Fri May 14 08:27:38 CST 2021, time=2021-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1619605, encodeId=4c3c161960529, content=<a href='/topic/show?id=8dd46061824' target=_blank style='color:#2F92EE;'>#有效治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=60618, encryptionId=8dd46061824, topicName=有效治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Fri May 14 08:27:38 CST 2021, time=2021-05-14, status=1, ipAttribution=), 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encryptionId=23e3454e353, topicName=学习)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9e3a5478833, createdName=ms5000000790714074, createdTime=Wed May 12 19:47:21 CST 2021, time=2021-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=964964, encodeId=6f8596496403, content=学习了!!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210606/3360b859ba944059aaffe8a1847ab57b/e91f325d086a40b2b9805211738111d1.jpg, createdBy=b3982392941, createdName=牟德武, createdTime=Wed May 12 17:32:01 CST 2021, time=2021-05-12, status=1, ipAttribution=)]
    2021-05-14 智智灵药
  7. 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  8. 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encryptionId=23e3454e353, topicName=学习)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9e3a5478833, createdName=ms5000000790714074, createdTime=Wed May 12 19:47:21 CST 2021, time=2021-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=964964, encodeId=6f8596496403, content=学习了!!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210606/3360b859ba944059aaffe8a1847ab57b/e91f325d086a40b2b9805211738111d1.jpg, createdBy=b3982392941, createdName=牟德武, createdTime=Wed May 12 17:32:01 CST 2021, time=2021-05-12, status=1, ipAttribution=)]
    2021-05-14 zhouqu_8
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encryptionId=23e3454e353, topicName=学习)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9e3a5478833, createdName=ms5000000790714074, createdTime=Wed May 12 19:47:21 CST 2021, time=2021-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=964964, encodeId=6f8596496403, content=学习了!!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210606/3360b859ba944059aaffe8a1847ab57b/e91f325d086a40b2b9805211738111d1.jpg, createdBy=b3982392941, createdName=牟德武, createdTime=Wed May 12 17:32:01 CST 2021, time=2021-05-12, status=1, ipAttribution=)]
    2021-05-12 ms5000000790714074

    受益匪浅#学习#

    0

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target=_blank style='color:#2F92EE;'>#BRCA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3684, encryptionId=63cc368459, topicName=BRCA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=智智灵药, createdTime=Fri May 14 08:27:38 CST 2021, time=2021-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1619605, encodeId=4c3c161960529, content=<a href='/topic/show?id=8dd46061824' target=_blank style='color:#2F92EE;'>#有效治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=60618, encryptionId=8dd46061824, topicName=有效治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Fri May 14 08:27:38 CST 2021, time=2021-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1621435, encodeId=36ca162143596, content=<a href='/topic/show?id=8f7d1368929' target=_blank style='color:#2F92EE;'>#PALB2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13689, encryptionId=8f7d1368929, topicName=PALB2)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Fri May 14 08:27:38 CST 2021, time=2021-05-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=964986, encodeId=01ff96498684, content=受益匪浅<a href='/topic/show?id=23e3454e353' target=_blank style='color:#2F92EE;'>#学习#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=45473, encryptionId=23e3454e353, topicName=学习)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9e3a5478833, createdName=ms5000000790714074, createdTime=Wed May 12 19:47:21 CST 2021, time=2021-05-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=964964, encodeId=6f8596496403, content=学习了!!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210606/3360b859ba944059aaffe8a1847ab57b/e91f325d086a40b2b9805211738111d1.jpg, createdBy=b3982392941, createdName=牟德武, createdTime=Wed May 12 17:32:01 CST 2021, time=2021-05-12, status=1, ipAttribution=)]
    2021-05-12 牟德武

    学习了!!!!

    0

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