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Clin Cancer Res:色瑞替尼对ALK阳性的非小细胞肺癌有显著的抗肿瘤活性

2015-03-04 范伟译 MedSci原创

目的:间变性淋巴瘤激酶(ALK)的重组在针对ALK抑制剂克唑替尼和色瑞替尼敏感性的非小细胞肺癌(NSCLC)上是重要的靶标。为确定克唑替尼和色瑞替尼先后次序的治疗效果,我们对采用两种药剂治疗ALK阳性患者的案例进行了回顾性分析。 实验设计:我们确定了四个机构中由克唑替尼和色瑞替尼治疗的73名ALK阳性的非小细胞肺癌患者。对克唑替尼和色瑞替尼治疗的医疗记录进行了审查,确定总生存期(OS)和无进展生

目的:间变性淋巴瘤激酶(ALK)的重组在针对ALK抑制剂克唑替尼和色瑞替尼敏感性的非小细胞肺癌(NSCLC)上是重要的靶标。为确定克唑替尼和色瑞替尼先后次序的治疗效果,我们对采用两种药剂治疗ALK阳性患者的案例进行了回顾性分析。

实验设计:我们确定了四个机构中由克唑替尼和色瑞替尼治疗的73名ALK阳性的非小细胞肺癌患者。对克唑替尼和色瑞替尼治疗的医疗记录进行了审查,确定总生存期(OS)和无进展生存期(PFS)。

结果:73例ALK阳性的患者中,克唑替尼的中位无进展生存期(mPFS)是8.2个月[95% 置信区间(CI)7.4-10.6 ]。从克唑替尼停药到色瑞替尼开始治疗时间间隔的中位数为25天(范围1-694)。色瑞替尼的中位无进展生存期是7.8个月(6.5-9.1)。在53例克唑替尼和色瑞替尼之间无间隔疗法中,色瑞替尼的中位无进展生存期是7.8个月(5.4-9.8)。采用克唑替尼和色瑞替尼先后次序治疗的中位组合无进展生存期是17.4个月(15.5-19.4)。23例接受克唑替尼后活检/色瑞替尼前活检的患者,色瑞替尼治疗有或无ALK抵抗突变的患者无进展生存期没有差异(mPFS 分别为5.8个月vs 6.5个月;P = 0.510)。在总体研究人群中,中位总生存期为49.4个月(35.5-63.1)。

结论:色瑞替尼对ALK阳性的非小细胞肺癌即使是之前采用克唑替尼治疗后采用色瑞替尼治疗的患者具有显著的抗肿瘤活性(中位组合无进展生存期为17.0个月)。额外的研究需要进一步确定具体的ALK耐药突变对色瑞替尼耐受反应的影响。

原始出处

Gainor JF, Tan DS, De Pas T, Solomon B, Ahmad A, Lazzari C, De Marinis F, Spitaleri G, Schultz K, Friboulet L, Yeap BY, Engelman JA, Shaw AT. Progression-Free and Overall Survival in ALK-Positive NSCLC Patients Treated with Sequential Crizotinib and Ceritinib. Clin Cancer Res. 2015 Feb 27. pii: clincanres.3009.2014.

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    2015-12-16 xjy02
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  5. [GetPortalCommentsPageByObjectIdResponse(id=1987512, encodeId=a68a198e512e2, content=<a href='/topic/show?id=540623233e' target=_blank style='color:#2F92EE;'>#ALK阳性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2323, encryptionId=540623233e, topicName=ALK阳性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Wed Dec 16 23:50:00 CST 2015, time=2015-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2059497, encodeId=9a1f205949ede, 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=61, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99381, encryptionId=2cc599381bd, topicName=非小细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=智智灵药, createdTime=Thu Jan 07 13:50:00 CST 2016, time=2016-01-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2034515, encodeId=b6052034515dc, content=<a href='/topic/show?id=3a9382989a2' target=_blank style='color:#2F92EE;'>#肿瘤活性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82989, encryptionId=3a9382989a2, topicName=肿瘤活性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=医者仁心, createdTime=Tue Jun 09 03:50:00 CST 2015, time=2015-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1674938, encodeId=dcc416e49387a, content=<a href='/topic/show?id=5521556518b' target=_blank style='color:#2F92EE;'>#抗肿瘤活性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55651, encryptionId=5521556518b, topicName=抗肿瘤活性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cf5227147934, createdName=cmj17wellington, createdTime=Wed Jul 29 11:50:00 CST 2015, time=2015-07-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=23744, encodeId=068223e447f, content=很不错学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=134, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=ac181616815, createdName=ljjj1053, createdTime=Sat May 16 19:58:00 CST 2015, time=2015-05-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2042517, encodeId=3f07204251e2c, content=<a href='/topic/show?id=676686e030a' target=_blank style='color:#2F92EE;'>#色瑞替尼#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86703, encryptionId=676686e030a, topicName=色瑞替尼)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=467c360, createdName=yuanming7, createdTime=Wed Oct 28 20:50:00 CST 2015, time=2015-10-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=17674, encodeId=a44e1e674f2, content=主要用于克唑替尼耐药后,再用色瑞替尼,这样患者的OS获益应该比较长。, beContent=null, objectType=article, channel=null, level=null, likeNumber=132, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Thu Mar 05 14:06:00 CST 2015, time=2015-03-05, status=1, ipAttribution=)]
    2015-05-16 ljjj1053

    很不错学习了

    0

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  7. [GetPortalCommentsPageByObjectIdResponse(id=1987512, encodeId=a68a198e512e2, content=<a href='/topic/show?id=540623233e' target=_blank style='color:#2F92EE;'>#ALK阳性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2323, encryptionId=540623233e, topicName=ALK阳性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Wed Dec 16 23:50:00 CST 2015, time=2015-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2059497, encodeId=9a1f205949ede, 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=61, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99381, encryptionId=2cc599381bd, topicName=非小细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=智智灵药, createdTime=Thu Jan 07 13:50:00 CST 2016, time=2016-01-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2034515, encodeId=b6052034515dc, content=<a href='/topic/show?id=3a9382989a2' target=_blank style='color:#2F92EE;'>#肿瘤活性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82989, encryptionId=3a9382989a2, topicName=肿瘤活性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=医者仁心, createdTime=Tue Jun 09 03:50:00 CST 2015, time=2015-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1674938, encodeId=dcc416e49387a, content=<a href='/topic/show?id=5521556518b' target=_blank style='color:#2F92EE;'>#抗肿瘤活性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55651, encryptionId=5521556518b, topicName=抗肿瘤活性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cf5227147934, createdName=cmj17wellington, createdTime=Wed Jul 29 11:50:00 CST 2015, time=2015-07-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=23744, encodeId=068223e447f, content=很不错学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=134, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=ac181616815, createdName=ljjj1053, createdTime=Sat May 16 19:58:00 CST 2015, time=2015-05-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2042517, encodeId=3f07204251e2c, content=<a href='/topic/show?id=676686e030a' target=_blank style='color:#2F92EE;'>#色瑞替尼#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86703, encryptionId=676686e030a, topicName=色瑞替尼)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=467c360, createdName=yuanming7, createdTime=Wed Oct 28 20:50:00 CST 2015, time=2015-10-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=17674, encodeId=a44e1e674f2, content=主要用于克唑替尼耐药后,再用色瑞替尼,这样患者的OS获益应该比较长。, beContent=null, objectType=article, channel=null, level=null, likeNumber=132, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Thu Mar 05 14:06:00 CST 2015, time=2015-03-05, status=1, ipAttribution=)]
    2015-03-05 lovetcm

    主要用于克唑替尼耐药后,再用色瑞替尼,这样患者的OS获益应该比较长。

    0

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Bristol-Myers Squibb最新PD1抑制药物ornivolumab(Opdivo),原本用于黑色素瘤,最新一项研究用于鳞状非小细胞肺癌的结果显示,在总生存期方面显著优于传统的化疗药物紫杉醇,该试验在早期阶段即中止研究,所有对照组患者全部转向ornivolumab治疗。这项研究给鳞状非小细胞肺癌的治疗带来巨大的变化,这是鳞状非小细胞肺癌近几十年来最大的突破之一。该药物有望被FDA优先审

JTO:Alectinib能用于ALK阳性的耐药的非小细胞肺癌脑转移治疗

Crizotinib和 Ceritinib是两种重要的ALK抑制剂,主要用于ALK阳性的非小细胞肺癌(NSCLC),然而,也面临患者快速耐药问题。以往研究表明Ceritinib对Crizotinib耐药的ALK阳性的NSCLC患者。那么,患者也对Ceritinib耐药,该如何处理呢?下一代ALK抑制剂Alectinib可能能解决这个问题。本研究发表在JTO上,主要用于ALK重排阳性的NSCLC患者

Lancet Oncology:III期临床试验显示非小细胞肺癌治疗现有方案仍最理想

肺癌是世界上最常见的恶性肿瘤之一,非小细胞肺癌约占所有肺癌的80 %,约75 %的患者发现时已处于中晚期,5年生存率很低。化疗与放射治疗是肺癌的主要治疗方法。为了探究对不能进行手术的III期非小细胞肺癌患者进行标准剂量或高剂量适形放射治疗同时给予卡铂与紫杉醇化疗以及额外补充西妥昔单抗的治疗效果,比较整体生存率,美国华盛顿大学的Jeffrey D Bradley研究组牵头,美国和加拿大共185个

Lung Cancer:EGFR酪氨酸激酶抑制剂用于EGFR阳性突变的非小细胞肺癌的安全性分析

目的:三个表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKIs)- 阿法替尼,厄洛替尼,和吉非替尼用于EGFR阳性突变的非小细胞肺癌(NSCLC)患者的治疗。由于患者长期接触表皮生长因子受体酪氨酸激酶抑制剂,这些药物对这些人产生的毒理学性质可能不同于那些未长期接触的患者。我们对这三个表皮生长因子受体酪氨酸激酶抑制剂治疗EGFR阳性突变的NSCLC患者发生严重不良反应的频率(AES)进行比较。

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