Clin Cancer Res:第三代EGFR-TKI Abvertinib治疗EGFR T790M+ NSCLC的活性和安全性

2021-11-09 Nebula MedSci原创

Abvertinib 300mg(2/日)在携带EGFR T790M突变的NSCLC患者中具有可观的临床活性,而且副反应可控

表皮生长因子受体酪氨酸激酶抑制剂 (EGFR-TKIs) 已被明确作为携带EGFR突变的非小细胞肺癌(NSCLC)患者的标准疗法。与接受化学治疗的患者相比,接受EGFR-TKIs(包括吉非替尼、阿法替尼和达克替尼)的患者的无进展生存率、缓解率和生活治疗均有所提高,而且副作用少。

Abvertinib (AC0010) 是一种基于吡啶嘧啶的第三代EGFR-TKI制剂,结构不同于第三代EGFR靶向药奥西替尼,可选择性地抑制EGFR激活性突变和T790M突变,与野生型EGFR相比,效价高达298倍。

本研究是一项在中国开展的多中心、开放标签的1-2期临床试验,旨在明确Abvertinib在1期试验中的最大推荐剂量(RP2D);在2期试验中评估Abvertinib用于既往接受EGFR抑制剂治疗后病情进展的携带EGFR T790M突变的NSCLC患者的活性和安全性。

该试验共招募了367位成年患者。在1期阶段,患者接受50mg-350mg的Abvertinib口服(2/日),28天为一疗程;2期试验采用Abvertinib 的最大推荐剂量,21天为一疗程。主要终点包括1期的RP2D和2期阶段的客观缓解率(ORR)。

可评估患者的最佳反应情况

在1期阶段,基于药代动力学、疗效和安全性,Abvertinib的最大推荐剂量被定为300mg(2/日)。在2期阶段,共有227位患者接受了Abvertinib 300mg(2/日)治疗,中位持续治疗时间为24.6周(范围0.43-129)。在209位可评估反应性的患者中,确认的客观缓解率为52.2%,疾病控制率(DCR)为88.0%。中位缓解持续时间(DoR)和无进展生存期(PFS)分别是8.5个月和7.5个月。中位总生存期(OS)是24.9个月。

无进展生存率

所有患者都至少报告了一次副反应事件,其中96.9%的患者发生过治疗相关性副反应。13.7%的患者报告了严重的治疗相关副反应。10位(4.4%)患者死亡,但无一例被认定与治疗相关。

总而言之,该研究表明,Abvertinib 300mg(2/日)在携带EGFR T790M突变的NSCLC患者中具有可观的临床活性,而且副反应可控

原始出处:

Zhou Qing,Wu Lin,Hu Pei et al. A novel third generation EGFR tyrosine kinase inhibitor Abivertinib for EGFR T790M mutant Non-Small Cell Lung Cancer: a multicenter phase1/2 study.[J] .Clin Cancer Res, 2021, https://doi.org/10.1158/1078-0432.CCR-21-2595

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    2022-09-13 zhlpower
  2. [GetPortalCommentsPageByObjectIdResponse(id=1795265, encodeId=ed7c1e9526535, content=<a href='/topic/show?id=98f91e05925' target=_blank style='color:#2F92EE;'>#T790M#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17059, encryptionId=98f91e05925, topicName=T790M)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c838337, createdName=zhlpower, createdTime=Tue Sep 13 15:10:53 CST 2022, time=2022-09-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1070983, encodeId=c81b10e098394, content=学习了。, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cbcd5675699, createdName=moyanju2796, createdTime=Wed Nov 17 08:31:11 CST 2021, time=2021-11-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1383093, encodeId=db38138309386, content=<a href='/topic/show?id=0c8265e2b3' target=_blank style='color:#2F92EE;'>#EGFR-TKI#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6572, encryptionId=0c8265e2b3, topicName=EGFR-TKI)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=hb2008ye, createdTime=Thu Nov 11 07:10:53 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1384238, encodeId=7164138423831, content=<a href='/topic/show?id=14bb1e503a0' target=_blank style='color:#2F92EE;'>#TKI#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17503, encryptionId=14bb1e503a0, topicName=TKI)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b73f484, createdName=lsj628, createdTime=Thu Nov 11 07:10:53 CST 2021, time=2021-11-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1534583, encodeId=621715345833c, content=<a href='/topic/show?id=22b3e9887e' target=_blank style='color:#2F92EE;'>#GFR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7988, encryptionId=22b3e9887e, topicName=GFR)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0a812532020, createdName=liuyiping, createdTime=Thu Nov 11 07:10:53 CST 2021, time=2021-11-11, status=1, ipAttribution=)]
    2021-11-17 moyanju2796

    学习了。

    0

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    2021-11-11 hb2008ye
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    2021-11-11 lsj628
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    2021-11-11 liuyiping

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