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Transl Lung Cancer Res: TP53共突变(TP53 mt+)对携带T790M耐药突变的EGFR mt+ NSCLC患者二线或以上使用奥希替尼治疗的影响

2022-02-08 yd2015 MedSci原创

研究表明,在EGFR mt+和T790M耐药突变的患者中,使用奥希替尼治疗,TP53 mt+对PFS和OS有负性预测作用。

在EGFR突变(EGFR mt+)的非小细胞肺癌(NSCLC)中,TP53共突变(TP53 mt+)的阴性预后和预测价值正日益被认识。数据一致表明,TP53 mt+对一线使用第一代和第二代酪氨酸激酶抑制剂(TKI)治疗的客观缓解率(ORR)、无进展生存期(PFS)和总生存期(OS)有负面预测作用。

然而,其对使用第三代TKI Osimertinib(奥希替尼)治疗的预测作用尚不明确。因此,有来自德国的团队开展了相关研究,评估TP53 mt+对携带T790M耐药突变的EGFR mt+ NSCLC患者二线或以上使用奥希替尼治疗的影响。相关结果发表在Translational Lung Cancer Research杂志上。

研究纳入77例IV期EGFR mt+ NSCLC 患者,所有77例(100%)患者均为敏感突变,为del19 (n=58/77;75%)或L858R (n=19/77;25%)。EGFR mt+的存在与女性(n=50/77;65%)和从未/轻度吸烟情况(n=54/77;71.4%)相关。在32/77例(42%)患者中发现TP53 mt+。37 /77(48%)例患者在开始使用奥希替尼前接受了阿法替尼、34/77(44.1%)厄洛替尼和6/77(7.8%)吉非替尼治疗。中位年龄为64岁(范围为28-92岁)。所有患者(n=77)在T790M发生时二线(n=51)或后线治疗(n=26)接受奥希替尼治疗。

在二线或后线治疗中,奥希替尼的ORR为45% (n=32/72), 39% (n=28/72)的患者疾病稳定(SD), 16.7% (n=12/72)的患者疾病进展。根据TP53状态分层,38% (n=11/29) TP53 mt+的患者和49% (n=21/43) TP53WT的患者在二线或后线治疗中获得ORR(完全缓解(CR)/部分缓解(PR))。

TP53 mt+患者采用第1代或第2代TKI的一线治疗PFS为13个月(n=31),而TP53WT患者PFS为17个月(n=39) (P=0.249)。在奥希替尼二线及后线治疗中,EGFR del19突变患者与EGFR L858R突变患者的中位PFS类似,分别为11个月(n=19)和10个月(n=53)(P = 0.957)。

根据TP53状态分层,在奥希替尼二线及后线治疗中,TP53 mt+患者的中位PFS较TP53WT患者显著缩短(9个月 vs 14个月,P=0.008)。

从最初诊断开始,整个队列的中位OS为46个月。与L858R突变患者相比,EGFR del 19突变患者的中位OS在数值上更长,从二线及后线治疗开始计算[22个月(n=53)],而L858R突变患者[15个月(n=19)],但差异无统计学意义(P=0.223)。

当根据TP53状态分层时,在奥希替尼二线及后线治疗中,TP53 mt+患者的中位OS显著缩短(16个月,n=32),而TP53WT患者的中位OS则为24个月(n=45) (P=0.025)。

TP53 mt+是PFS (HR 0.393; P=0.003)和OS(HR 0.352;P=0.002)有统计学意义的独立阴性预测因素。

综上,研究表明,在EGFR mt+和T790M耐药突变的患者中,使用奥希替尼治疗,TP53 mt+对PFS和OS有负性预测作用。

 

原始出处:

Roeper J, Christopoulos P, Falk M, Heukamp LC, Tiemann M, Stenzinger A, Thomas M, Griesinger F. TP53 co-mutations as an independent prognostic factor in 2nd and further line therapy—EGFR mutated non-small cell lung cancer IV patients treated with osimertinib. Transl Lung Cancer Res 2022;11(1):4-13. doi: 10.21037/tlcr-21-754

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    2022-06-18 bsmagic9140
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    2022-11-13 zhlpower
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  5. [GetPortalCommentsPageByObjectIdResponse(id=1657604, encodeId=174d165e60417, content=<a href='/topic/show?id=3ca31e71903' target=_blank style='color:#2F92EE;'>#TRA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=117, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17719, encryptionId=3ca31e71903, topicName=TRA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=757b24868428, createdName=bsmagic9140, createdTime=Sat Jun 18 17:03:54 CST 2022, time=2022-06-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1795271, encodeId=f7a41e95271c7, content=<a href='/topic/show?id=98f91e05925' target=_blank style='color:#2F92EE;'>#T790M#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17059, encryptionId=98f91e05925, topicName=T790M)], attachment=null, authenticateStatus=null, createdAvatar=, 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  6. 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time=2022-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1458463, encodeId=7a8e1458463a8, content=<a href='/topic/show?id=50a81e6869e' target=_blank style='color:#2F92EE;'>#TP53#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17686, encryptionId=50a81e6869e, topicName=TP53)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2d276073420, createdName=zblhy, createdTime=Wed Feb 09 11:03:54 CST 2022, time=2022-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1534616, encodeId=aa191534616ee, content=<a href='/topic/show?id=22b3e9887e' target=_blank style='color:#2F92EE;'>#GFR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, 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=Wed Feb 09 11:03:54 CST 2022, time=2022-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1191138, encodeId=60ac119113865, content=新技术,有推广价值, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=89ae6481716, createdName=ms3000000637975859, createdTime=Tue Feb 08 19:40:28 CST 2022, time=2022-02-08, status=1, ipAttribution=)]
    2022-02-09 zhishijing
  7. 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time=2022-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1458463, encodeId=7a8e1458463a8, content=<a href='/topic/show?id=50a81e6869e' target=_blank style='color:#2F92EE;'>#TP53#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17686, encryptionId=50a81e6869e, topicName=TP53)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2d276073420, createdName=zblhy, createdTime=Wed Feb 09 11:03:54 CST 2022, time=2022-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1534616, encodeId=aa191534616ee, content=<a href='/topic/show?id=22b3e9887e' target=_blank style='color:#2F92EE;'>#GFR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, 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=Wed Feb 09 11:03:54 CST 2022, time=2022-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1191138, encodeId=60ac119113865, content=新技术,有推广价值, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=89ae6481716, createdName=ms3000000637975859, createdTime=Tue Feb 08 19:40:28 CST 2022, time=2022-02-08, status=1, ipAttribution=)]
  8. [GetPortalCommentsPageByObjectIdResponse(id=1657604, encodeId=174d165e60417, content=<a href='/topic/show?id=3ca31e71903' target=_blank style='color:#2F92EE;'>#TRA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=117, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17719, encryptionId=3ca31e71903, topicName=TRA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=757b24868428, createdName=bsmagic9140, createdTime=Sat Jun 18 17:03:54 CST 2022, time=2022-06-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1795271, encodeId=f7a41e95271c7, content=<a href='/topic/show?id=98f91e05925' target=_blank style='color:#2F92EE;'>#T790M#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17059, encryptionId=98f91e05925, topicName=T790M)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c838337, createdName=zhlpower, createdTime=Sun Nov 13 07:03:54 CST 2022, time=2022-11-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1795276, encodeId=b1951e952761a, content=<a href='/topic/show?id=66d21e06102' target=_blank style='color:#2F92EE;'>#T790M耐药#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17061, encryptionId=66d21e06102, topicName=T790M耐药)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6595338, createdName=xuruicheng, createdTime=Sun Dec 18 12:03:54 CST 2022, time=2022-12-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2067611, encodeId=1a5a206e61117, content=<a href='/topic/show?id=d0841e75535' target=_blank style='color:#2F92EE;'>#Transl#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17755, encryptionId=d0841e75535, topicName=Transl)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/101173734/363C99735735B7F4CB11D5F78F580525/100, createdBy=aab22500211, createdName=ms3025846204744509, createdTime=Sat Mar 19 19:03:54 CST 2022, time=2022-03-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2069063, encodeId=b35b20690634e, content=<a href='/topic/show?id=bbd816043f2' target=_blank style='color:#2F92EE;'>#SCLC患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16043, encryptionId=bbd816043f2, topicName=SCLC患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Mon Apr 11 21:03:54 CST 2022, time=2022-04-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1372458, encodeId=85c713e2458fa, content=<a href='/topic/show?id=9d861362e53' target=_blank style='color:#2F92EE;'>#p53#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=119, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13627, encryptionId=9d861362e53, topicName=p53)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5d70341, createdName=zhishijing, createdTime=Wed Feb 09 11:03:54 CST 2022, time=2022-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1410919, encodeId=90c214109192e, content=<a href='/topic/show?id=a4ed130e7d0' target=_blank style='color:#2F92EE;'>#NSCLC患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13077, encryptionId=a4ed130e7d0, topicName=NSCLC患者)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=06332789533, createdName=xiongliangxl, createdTime=Wed Feb 09 11:03:54 CST 2022, time=2022-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1458463, encodeId=7a8e1458463a8, content=<a href='/topic/show?id=50a81e6869e' target=_blank style='color:#2F92EE;'>#TP53#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17686, encryptionId=50a81e6869e, topicName=TP53)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2d276073420, createdName=zblhy, createdTime=Wed Feb 09 11:03:54 CST 2022, time=2022-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1534616, encodeId=aa191534616ee, content=<a href='/topic/show?id=22b3e9887e' target=_blank style='color:#2F92EE;'>#GFR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, 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=Wed Feb 09 11:03:54 CST 2022, time=2022-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1191138, encodeId=60ac119113865, content=新技术,有推广价值, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=89ae6481716, createdName=ms3000000637975859, createdTime=Tue Feb 08 19:40:28 CST 2022, time=2022-02-08, status=1, ipAttribution=)]
    2022-02-09 zblhy
  9. [GetPortalCommentsPageByObjectIdResponse(id=1657604, encodeId=174d165e60417, content=<a href='/topic/show?id=3ca31e71903' target=_blank style='color:#2F92EE;'>#TRA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=117, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17719, encryptionId=3ca31e71903, topicName=TRA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=757b24868428, createdName=bsmagic9140, createdTime=Sat Jun 18 17:03:54 CST 2022, time=2022-06-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1795271, encodeId=f7a41e95271c7, content=<a href='/topic/show?id=98f91e05925' target=_blank style='color:#2F92EE;'>#T790M#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=93, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17059, encryptionId=98f91e05925, topicName=T790M)], attachment=null, authenticateStatus=null, createdAvatar=, 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href='/topic/show?id=9d861362e53' target=_blank style='color:#2F92EE;'>#p53#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=119, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13627, encryptionId=9d861362e53, topicName=p53)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5d70341, createdName=zhishijing, createdTime=Wed Feb 09 11:03:54 CST 2022, time=2022-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1410919, encodeId=90c214109192e, content=<a href='/topic/show?id=a4ed130e7d0' target=_blank style='color:#2F92EE;'>#NSCLC患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13077, encryptionId=a4ed130e7d0, topicName=NSCLC患者)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=06332789533, createdName=xiongliangxl, createdTime=Wed Feb 09 11:03:54 CST 2022, time=2022-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1458463, encodeId=7a8e1458463a8, content=<a href='/topic/show?id=50a81e6869e' target=_blank style='color:#2F92EE;'>#TP53#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17686, encryptionId=50a81e6869e, topicName=TP53)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2d276073420, createdName=zblhy, createdTime=Wed Feb 09 11:03:54 CST 2022, time=2022-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1534616, encodeId=aa191534616ee, content=<a href='/topic/show?id=22b3e9887e' target=_blank style='color:#2F92EE;'>#GFR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, 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=Wed Feb 09 11:03:54 CST 2022, time=2022-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1191138, encodeId=60ac119113865, content=新技术,有推广价值, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=89ae6481716, createdName=ms3000000637975859, createdTime=Tue Feb 08 19:40:28 CST 2022, time=2022-02-08, status=1, ipAttribution=)]
    2022-02-09 liuyiping
  10. 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topicList=[TopicDto(id=17755, encryptionId=d0841e75535, topicName=Transl)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/101173734/363C99735735B7F4CB11D5F78F580525/100, createdBy=aab22500211, createdName=ms3025846204744509, createdTime=Sat Mar 19 19:03:54 CST 2022, time=2022-03-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2069063, encodeId=b35b20690634e, content=<a href='/topic/show?id=bbd816043f2' target=_blank style='color:#2F92EE;'>#SCLC患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16043, encryptionId=bbd816043f2, topicName=SCLC患者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Mon Apr 11 21:03:54 CST 2022, time=2022-04-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1372458, encodeId=85c713e2458fa, content=<a href='/topic/show?id=9d861362e53' target=_blank style='color:#2F92EE;'>#p53#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=119, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13627, encryptionId=9d861362e53, topicName=p53)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5d70341, createdName=zhishijing, createdTime=Wed Feb 09 11:03:54 CST 2022, time=2022-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1410919, encodeId=90c214109192e, content=<a href='/topic/show?id=a4ed130e7d0' target=_blank style='color:#2F92EE;'>#NSCLC患者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13077, encryptionId=a4ed130e7d0, topicName=NSCLC患者)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=06332789533, createdName=xiongliangxl, createdTime=Wed Feb 09 11:03:54 CST 2022, time=2022-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1458463, encodeId=7a8e1458463a8, content=<a href='/topic/show?id=50a81e6869e' target=_blank style='color:#2F92EE;'>#TP53#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=97, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17686, encryptionId=50a81e6869e, topicName=TP53)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2d276073420, createdName=zblhy, createdTime=Wed Feb 09 11:03:54 CST 2022, time=2022-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1534616, encodeId=aa191534616ee, content=<a href='/topic/show?id=22b3e9887e' target=_blank style='color:#2F92EE;'>#GFR#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=99, 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=Wed Feb 09 11:03:54 CST 2022, time=2022-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1191138, encodeId=60ac119113865, content=新技术,有推广价值, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=89ae6481716, createdName=ms3000000637975859, createdTime=Tue Feb 08 19:40:28 CST 2022, time=2022-02-08, status=1, ipAttribution=)]
    2022-02-08 ms3000000637975859

    新技术,有推广价值

    0

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