ASCO2021:Patritumab Deruxtecan在EGFR抑制剂耐药、EGFR突变的非小细胞肺癌患者中产生持久反应

2021-06-08 MedSci原创 MedSci原创

Patritumab deruxtecan在非小细胞肺癌患者中具有持久的疗效

一项I期剂量递增和剂量扩大研究(U31402-A-U102,)的结果显示,Patritumab deruxtecan在非小细胞肺癌患者中具有持久的疗效,无论EGFR酪氨酸激酶抑制剂耐药机制如何。

对于EGFR抑制剂耐药、EGFR突变(EGFRm)非小细胞肺癌(NSCLC)患者的有效治疗受到了标准护理EGFR酪氨酸激酶抑制剂(TKIs)获得性耐药性发展的阻碍。在2021年ASCO年会上的报告中,Dana-Farber癌症研究所的Pasi A. Jänne医学博士解释说,这些耐药机制包括靶向机制和旁路改变,但注意到在许多患者中没有特异性的耐药机制可以被识别。 EGFR TKIs后的铂基化疗疗效有限,一般而言,EGFR TKIs和铂基化疗后的挽救性治疗也疗效有限。因此,对于EGFR抑制剂耐药的EGFRm NSCLC需要更有效的治疗方法。

HER3-DXd是一种人抗HER3 IgG1单克隆抗体,用于临床评估NSCLC、转移性乳腺癌结直肠癌。HER3在绝大多数非小细胞肺癌中表达,重要的是,目前还不知道HER3的改变是EGFRm非小细胞肺癌对EGFR TKIs耐药的机制。

Patritumab Deruxtecan活性和患者既往治疗结果

该研究包括57例EGFR TKI耐药患者,EGFRm NSCLC患者使用5.6 mg/kg HER3-DXd进行剂量递增(12例)和剂量扩大队列1(45例)。所有患者都接受了大量的术前治疗,并且所有患者之前都接受了EGFR TKI治疗,其中大多数患者之前也接受过铂类化疗,并且中位数之前接受过四种系统治疗。47%的患者有中枢神经系统转移史。表格显示了患者的治疗结果。

HER3-DXd的疗效在大量预处理的患者中是很高的,有39%的应答率和8.2个月的无进展生存。仍有待探索的问题是以前治疗序列的影响,以及颅内反应和无进展生存期的评估。

Jänne博士强调,“在具有可识别耐药机制的患者和没有可识别耐药机制但既往EGFR TKI治疗取得进展的患者中观察到了应答。”既往有脑转移和无脑转移的患者的客观有效率分别为32%和41%。总之,无论既往治疗或脑转移史如何,均观察到持续性反应。此外,在基线HER3表达谱中观察到临床反应

最常见的3级或更高级别的治疗紧急不良事件(发生在≥5%的患者中)是血液学毒性,如血小板减少、中性粒细胞计数减少、贫血和发热性中性粒细胞减少。其他副作用包括疲劳、缺氧和呼吸困难。21%接受5.6 mg/kg HER3-DXd治疗的患者和19%接受所有剂量治疗的患者中观察到严重的治疗紧急不良事件

总之,HER3-DXd解决了EGFR TKI耐药,EGFRm NSCLC中未满足的需求。疗效具有临床意义,具有持久疗效,有效率为39%,中位无进展生存期为18.2个月。在这些患者群体中观察到EGFR TKI耐药机制的疗效,这些患者通常难以治疗,且有多种耐药机制。”

Girard博士还强调了HER3-DXd在不同耐药机制中的功效。他说:“这项研究的惊人发现实际上是HER3-DXd在所有报道的耐药机制中的有效性EGFR相关的总缓解率为47%,而非EGFR, MET相关的患者的总缓解率为45%。”“在这项研究中,MET扩增的患者数量有限。预测性生物标志物仍有待评估;在这种情况下,HER3免疫组化似乎不是候选者。”

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    2021-09-18 shock_melon
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time=2021-06-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600894, encodeId=804e1600894ba, content=<a href='/topic/show?id=973e99390a4' target=_blank style='color:#2F92EE;'>#非小细胞肺癌患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99390, encryptionId=973e99390a4, topicName=非小细胞肺癌患者)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2e0218815946, createdName=zxxiang, createdTime=Thu Jun 10 12:16:10 CST 2021, time=2021-06-10, status=1, ipAttribution=)]
  4. 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time=2021-06-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600894, encodeId=804e1600894ba, content=<a href='/topic/show?id=973e99390a4' target=_blank style='color:#2F92EE;'>#非小细胞肺癌患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99390, encryptionId=973e99390a4, topicName=非小细胞肺癌患者)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2e0218815946, createdName=zxxiang, createdTime=Thu Jun 10 12:16:10 CST 2021, time=2021-06-10, status=1, ipAttribution=)]
    2021-06-25 jklm09
  5. 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time=2021-06-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600894, encodeId=804e1600894ba, content=<a href='/topic/show?id=973e99390a4' target=_blank style='color:#2F92EE;'>#非小细胞肺癌患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99390, encryptionId=973e99390a4, topicName=非小细胞肺癌患者)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2e0218815946, createdName=zxxiang, createdTime=Thu Jun 10 12:16:10 CST 2021, time=2021-06-10, status=1, ipAttribution=)]
    2022-04-01 docwu2019
  6. 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time=2021-06-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600894, encodeId=804e1600894ba, content=<a href='/topic/show?id=973e99390a4' target=_blank style='color:#2F92EE;'>#非小细胞肺癌患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99390, encryptionId=973e99390a4, topicName=非小细胞肺癌患者)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2e0218815946, createdName=zxxiang, createdTime=Thu Jun 10 12:16:10 CST 2021, time=2021-06-10, status=1, ipAttribution=)]
    2021-06-12 quxin068
  7. 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topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Fri Jun 25 04:16:10 CST 2021, time=2021-06-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1912619, encodeId=e05d19126197e, content=<a href='/topic/show?id=4de7112046c' target=_blank style='color:#2F92EE;'>#mAb#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11204, encryptionId=4de7112046c, topicName=mAb)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Fri Apr 01 00:16:10 CST 2022, time=2022-04-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1939213, encodeId=4beb193921384, content=<a href='/topic/show?id=1c292818fd' target=_blank style='color:#2F92EE;'>#ASC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2818, encryptionId=1c292818fd, topicName=ASC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=74808, createdName=quxin068, createdTime=Sat Jun 12 22:16:10 CST 2021, time=2021-06-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1990755, encodeId=50e41990e5587, content=<a href='/topic/show?id=5739822223f' target=_blank style='color:#2F92EE;'>#肺癌患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82222, encryptionId=5739822223f, topicName=肺癌患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f612331, createdName=gds2009, createdTime=Sun Feb 13 22:16:10 CST 2022, time=2022-02-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1786783, encodeId=29b91e867830a, content=<a 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time=2021-06-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600894, encodeId=804e1600894ba, content=<a href='/topic/show?id=973e99390a4' target=_blank style='color:#2F92EE;'>#非小细胞肺癌患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99390, encryptionId=973e99390a4, topicName=非小细胞肺癌患者)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2e0218815946, createdName=zxxiang, createdTime=Thu Jun 10 12:16:10 CST 2021, time=2021-06-10, status=1, ipAttribution=)]
  8. [GetPortalCommentsPageByObjectIdResponse(id=1952129, encodeId=20e51952129df, content=<a href='/topic/show?id=e56658621e' target=_blank style='color:#2F92EE;'>#deruxtecan#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5862, encryptionId=e56658621e, topicName=deruxtecan)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1ce4238, createdName=dangious, createdTime=Fri May 06 06:16:10 CST 2022, time=2022-05-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1652485, encodeId=01be1652485b7, content=<a href='/topic/show?id=13d01e24509' target=_blank style='color:#2F92EE;'>#TEC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17245, encryptionId=13d01e24509, topicName=TEC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=852f24292001, createdName=shock_melon, createdTime=Sat Sep 18 12:16:10 CST 2021, time=2021-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2059986, encodeId=28702059986fd, content=<a href='/topic/show?id=2cc599381bd' target=_blank style='color:#2F92EE;'>#非小细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99381, encryptionId=2cc599381bd, topicName=非小细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e07307, createdName=lingaifan, createdTime=Sun Jan 02 10:16:10 CST 2022, time=2022-01-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1852678, encodeId=533518526e808, 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=25, replyNumber=0, topicName=null, topicId=null, 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objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2818, encryptionId=1c292818fd, topicName=ASC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=74808, createdName=quxin068, createdTime=Sat Jun 12 22:16:10 CST 2021, time=2021-06-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1990755, encodeId=50e41990e5587, content=<a href='/topic/show?id=5739822223f' target=_blank style='color:#2F92EE;'>#肺癌患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82222, encryptionId=5739822223f, topicName=肺癌患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f612331, createdName=gds2009, createdTime=Sun Feb 13 22:16:10 CST 2022, time=2022-02-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1786783, encodeId=29b91e867830a, content=<a 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time=2021-06-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600894, encodeId=804e1600894ba, content=<a href='/topic/show?id=973e99390a4' target=_blank style='color:#2F92EE;'>#非小细胞肺癌患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99390, encryptionId=973e99390a4, topicName=非小细胞肺癌患者)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2e0218815946, createdName=zxxiang, createdTime=Thu Jun 10 12:16:10 CST 2021, time=2021-06-10, status=1, ipAttribution=)]
  9. [GetPortalCommentsPageByObjectIdResponse(id=1952129, encodeId=20e51952129df, content=<a href='/topic/show?id=e56658621e' target=_blank style='color:#2F92EE;'>#deruxtecan#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5862, encryptionId=e56658621e, topicName=deruxtecan)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1ce4238, createdName=dangious, createdTime=Fri May 06 06:16:10 CST 2022, time=2022-05-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1652485, encodeId=01be1652485b7, content=<a href='/topic/show?id=13d01e24509' target=_blank style='color:#2F92EE;'>#TEC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17245, encryptionId=13d01e24509, topicName=TEC)], attachment=null, authenticateStatus=null, createdAvatar=null, 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objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2818, encryptionId=1c292818fd, topicName=ASC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=74808, createdName=quxin068, createdTime=Sat Jun 12 22:16:10 CST 2021, time=2021-06-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1990755, encodeId=50e41990e5587, content=<a href='/topic/show?id=5739822223f' target=_blank style='color:#2F92EE;'>#肺癌患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82222, encryptionId=5739822223f, topicName=肺癌患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f612331, createdName=gds2009, createdTime=Sun Feb 13 22:16:10 CST 2022, time=2022-02-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1786783, encodeId=29b91e867830a, content=<a href='/topic/show?id=8f3b13801a6' target=_blank style='color:#2F92EE;'>#Patritumab#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13801, encryptionId=8f3b13801a6, topicName=Patritumab)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e0a1165, createdName=jiangfeng5067, createdTime=Fri Aug 13 13:16:10 CST 2021, time=2021-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1534550, encodeId=79f0153455064, content=<a href='/topic/show?id=22b3e9887e' target=_blank style='color:#2F92EE;'>#GFR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, 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 Jun 10 12:16:10 CST 2021, time=2021-06-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600894, encodeId=804e1600894ba, content=<a href='/topic/show?id=973e99390a4' target=_blank style='color:#2F92EE;'>#非小细胞肺癌患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99390, encryptionId=973e99390a4, topicName=非小细胞肺癌患者)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2e0218815946, createdName=zxxiang, createdTime=Thu Jun 10 12:16:10 CST 2021, time=2021-06-10, status=1, ipAttribution=)]
    2021-06-10 liuyiping
  10. 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