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Thorac Cancer:EGFR突变肺癌EGFR-TKIs治疗进展后应用免疫检查点抑制剂治疗的疗效

2021-12-19 yd2015 MedSci原创

研究表明,EGFR-TKI治疗进展后使用ICI治疗似乎对L858R亚型效果更佳。

晚期非小细胞肺癌(NSCLC)目前进入精准治疗时代。对于EGFR阳性患者,EGFR-TKI为标准一线治疗。但是对于EGFR-TKI治疗进展后使用免疫检查点抑制剂(ICIs)治疗的疗效尚不清楚。因此,有来自日本的学者开展了相关回顾性研究,评估EGFR阳性NSCLC患者使用EGFR-TKI进展后使用ICIs治疗的疗效。相关结果发表在Thoracic Cancer杂志上。

研究回顾性收集2015年12月-2020年3月期间符合条件的患者。研究共纳入25例患者。有15名男性(60%),中位年龄为67岁(38 - 80岁)。11例(44%)患者有吸烟史,10例(40%)患者术后复发。所有病例诊断时组织学类型均为腺癌。ICI单药治疗为nivolumab有21例,pembrolizumab有2例,atezolizumab有2例。ICI给药前PD-L1评分(TPS)低于1%的有8例(32%),1%或以上的有4例(16%),其余13例未评估。

ICI治疗的中位持续时间为1.4个月。所有患者按治疗时间分为两组,治疗时间小于90天为无反应组,≥90天为反应组。在无应答和有应答患者中,EGFR 19外显子缺失患者的比例分别为62.5%和11.1%;L858R 分别有25.0%和66.7%, T790M阳性分别为31.3%和33.3%。利率PD-L1阳性分别为12.5%和22.2%。

ICI治疗期间的最佳反应显示,有1例(4%)完全缓解(CR), 4例(16%)部分缓解(PR), 4例(16%)病情稳定(SD), 16例(64%)进展性疾病(PD)。ORR为20%,DCR为36%。比较不同EGFR亚型突变,EGFR 19外显子缺失和L858R的ORR分别为9.1%和30.0%,DCR分别为27.3%和50.0%。ICIs对L858R肿瘤具有较高的抗肿瘤作用。4例不常见突变或复合突变中,1例(25%)为PR, 3例(75%)为PD。此外,PD-L1阳性和PD-L1阴性患者的应答率无差异。有趣的是,在非吸烟者中观察到较高的应答率。

对于EGFR亚型,19外显子缺失组ICI治疗的中位持续时间为1.0个月(95% CI: 0.60-1.41), L858R组为3.3个月(95% CI: 0.98 5.62) (HR 0.35, 95% CI: 0.13 0.93, p = 0.026)。因此,L858R组的ICI治疗持续时间明显长于19号外显子缺失组。≥70岁患者较<70岁患者的ICIs治疗时间较长(HR 0.34, 95% CI: 0.12 0.95, p = 0.027)。而在性别或T790M亚组差异无统计学意义([HR 0.53, 95% CI: 0.21 1.31, p = 0.152], [HR = 0.59, 95% CI: 0.23 1.50, p = 0.255])。

ICI治疗开始的OS分析发现,19外显子缺失和L858R患者的中位OS分别为15.7个月(95% CI: 8.76 22.64)和14.8个月(95% CI: 0.00 34.61) (HR 1.00, 95% CI: 0.29 3.47, p = 0.997)。当比较ICI应答者和非应答者的OS时,应答者的OS较长。

综上,研究表明,EGFR-TKI治疗进展后使用ICI治疗似乎对L858R亚型效果更佳。

 

原始出处:

Takashi Ito, Hiromi Nagashima, Masachika Akiyama, et al. Treatment with immune checkpoint inhibitors after EGFR-TKIs in EGFR-mutated lung cancer. Thorac Cancer. 2021;1–8. DOI: 10.1111/1759-7714.14267.

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    2022-09-03 hbwxf
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    2022-07-30 yyj062
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    2022-07-01 jklm09
  4. 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createdName=cjlflight, createdTime=Mon Dec 20 16:21:51 CST 2021, time=2021-12-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1340597, encodeId=7e3b134059ed1, content=<a href='/topic/show?id=dd1a29055c8' target=_blank style='color:#2F92EE;'>#免疫检查点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29055, encryptionId=dd1a29055c8, topicName=免疫检查点)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKUdkK5dVTue7YQDvwqM1ugOuEpDZEzvXhoGClFiavehcrNAYDuPbks3MkKLPpyAEicgic80KguxwicYQ/132, createdBy=ec952500165, createdName=ms5187542471278033, createdTime=Fri Dec 17 10:55:19 CST 2021, time=2021-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1383098, encodeId=870f1383098ef, content=<a href='/topic/show?id=0c8265e2b3' target=_blank style='color:#2F92EE;'>#EGFR-TKI#</a>, beContent=null, 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content=<a href='/topic/show?id=22b3e9887e' target=_blank style='color:#2F92EE;'>#GFR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, 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=Fri Dec 17 10:55:19 CST 2021, time=2021-12-17, status=1, ipAttribution=)]
    2022-06-17 yhj-time
  5. 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content=<a href='/topic/show?id=22b3e9887e' target=_blank style='color:#2F92EE;'>#GFR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, 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=Fri Dec 17 10:55:19 CST 2021, time=2021-12-17, status=1, ipAttribution=)]
    2022-01-03 1361f79ee3m

    更新了知识,L858耐药后应用免疫效果比19缺失的效果更好,但OS二者相差不多

    0

  6. 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createdName=cjlflight, createdTime=Mon Dec 20 16:21:51 CST 2021, time=2021-12-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1340597, encodeId=7e3b134059ed1, content=<a href='/topic/show?id=dd1a29055c8' target=_blank style='color:#2F92EE;'>#免疫检查点#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29055, encryptionId=dd1a29055c8, topicName=免疫检查点)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTKUdkK5dVTue7YQDvwqM1ugOuEpDZEzvXhoGClFiavehcrNAYDuPbks3MkKLPpyAEicgic80KguxwicYQ/132, createdBy=ec952500165, createdName=ms5187542471278033, createdTime=Fri Dec 17 10:55:19 CST 2021, time=2021-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1383098, encodeId=870f1383098ef, content=<a href='/topic/show?id=0c8265e2b3' target=_blank style='color:#2F92EE;'>#EGFR-TKI#</a>, beContent=null, 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content=<a href='/topic/show?id=22b3e9887e' target=_blank style='color:#2F92EE;'>#GFR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=96, 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=Fri Dec 17 10:55:19 CST 2021, time=2021-12-17, status=1, ipAttribution=)]
    2021-12-20 cjlflight

    学习了

    0

  7. 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盐酸二甲双胍是一种新型的抗癌药物。预临床和回顾性研究表明,它可以改善包括肺癌在内的多种肿瘤的预后。特别是关于二甲双胍与表皮生长因子受体(EGFR)-酪氨酸激酶抑制剂(TKIs)之间的协同作用的证据越来越多。Arrieta等人开展一非盲的随机化2期试验,评估采用EGFR-TKIs联合二甲双胍治疗 vs 单纯EGFR-TKIs治疗的晚期肺腺癌患者的无进展生存期(PFS)。招募年满18岁的组织学确诊的无

Sci Rep:EGFR-TKIs治疗EGFR突变型非小细胞肺癌的神经生长因子表达及其临床意义

在EGFR突变型NSCLC患者中,可溶性神经生长因子与对第一代EGFR-TKIs耐药相关,而不是第二代EGFR-TKIs。

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