盘点:非小细胞肺癌近期重要研究进展一览

2018-04-12 MedSci MedSci原创

肺癌是我国的头号癌症杀手,在我国每年新增的65.3万例肺癌患者中,非小细胞肺癌(NSCLC)患者占到了85%。靶向药物出现以来,随着时间的推移,肺癌患者不可避免地出现了耐药、疾病进展等情况,迫切需要新型药物延长生命。这里梅斯小编整理了一些近期关于非小细胞肺癌的重要研究进展与大家一同分享。【1】贝伐单抗对非小细胞肺癌化疗效果如何近期,Radiology杂志发表的额一项研究验证了双输入灌注CT是否

肺癌是我国的头号癌症杀手,在我国每年新增的65.3万例肺癌患者中,非小细胞肺癌NSCLC)患者占到了85%。靶向药物出现以来,随着时间的推移,肺癌患者不可避免地出现了耐药、疾病进展等情况,迫切需要新型药物延长生命。这里梅斯小编整理了一些近期关于非小细胞肺癌的重要研究进展与大家一同分享。

【1】贝伐单抗对非小细胞肺癌化疗效果如何

近期,Radiology杂志发表的额一项研究验证了双输入灌注CT是否能预测进行化疗的非小细胞肺癌(NSCLC)患者的治疗反应和预后。研究共纳入了66例III期或IV期的NSCLC并行化疗的患者(男性42例,女性24例;平均年龄63.4岁)。根据治疗方法将患者分为3组:北伐单抗(BV)组(n=20)、非BV的铂类化疗药组(n=25)及非BV治疗组(n=21)。结果显示,在BV治疗组,治疗前BAP与两期化疗后的肿瘤减小率具有独立相关性(P = .006);治疗前BAP与高危死亡风险及病情进展具有明显相关性。在3组中,治疗前PAP及临床指标均不能预测放疗效果或预后。表明由双输入灌注CT获得的治疗前BAP可能有助于预测进行BV治疗的NSCLC患者的治疗反应。

【2】奥斯替尼一线治疗EGFR突变阳性非小细胞肺癌疗效显著

奥斯替尼为口服、第三代、不可逆、表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI),用于EGFR-TKI敏感性以及EGFR T790M耐药突变非小细胞肺癌。一项III期临床研究探究了奥斯替尼用于先前未经治疗的EGFR突变阳性晚期非小细胞肺癌的疗效。研究共纳入了556名未经治疗的EGFR突变阳性患者随机接受奥斯替尼(80mg每天1次)或标准EGFR-TKI(吉非替尼250mg每天1次或厄洛替尼150mg每天1次)。结果显示,奥斯替尼治疗可显著延长患者无进展生存期。组间客观缓解率相近。奥斯替尼平均响应时间为17.2个月,标准治疗为8.5个月。奥斯替尼组18个月的生存率为83%,标准治疗为71%。3级及以上不良事件率,奥斯替尼组为24%,标准治疗组为45%。表明奥斯替尼一线治疗EGFR突变阳性非小细胞肺癌的疗效显著优于现有疗法,其安全性高,不良事件少。

【3】血清EMMPRIN的表达或可用于非小细胞肺癌的检测

既往研究表明EMMPRIN过表达涉及肿瘤的恶性生物学行为。本研究旨在揭示EMMPRIN在非小细胞肺癌(NSCLC)中的表达状态及其对NSCLC的诊断价值。结果显示,NSCLC组织和血清中EMMPRIN的表达水平高于正常对照组,EMMPRIN的表达与NSCLC的淋巴结转移和晚期分期明显相关。ROC曲线表明,EMMPRIN用于区分非小细胞肺癌的阈值为80.3 pg/mL,敏感性为97.22%,特异性为95%。血清和组织中EMMPRIN的表达水平较高似乎是NSCLC发生的危险因素。表明EMMPRIN的过度表达与NSCLC的淋巴结转移和晚期相关,血清EMMPRIN的检测有助于NSCLC的诊断

【4】非小细胞肺癌患者抗PD-1/PD-L1阻断治疗反应的分子决定因素


使用免疫检查点抑制(ICI)治疗晚期非小细胞肺癌有持续的治疗反应,可以改善患者预后。目前尚需最大化ICI作用的临床工具以及进一步理解治疗反应的分子决定因素。二代测序(NGS)技术正变得越来越普遍,但是其在发掘ICI治疗反应预测分子领域的作用尚未知。为此,研究人员收集了接受抗PD-1或抗PD-L1治疗以及NGS的晚期非小细胞肺癌患者的临床数据。对比了DCB患者和无持续临床获益(NDB)患者的肿瘤突变负荷(TMB)以及基因改变情况。49例患者进行了全基因组测序(WES)以比较靶向NGS和WES对TMB量化情况的评估效果。研究结果表明,使用NGS评估TME与WES与WES相关性良好。DCB患者与NDB患者相比TMB更高。DCB更常见,TMB超过50%的患者无进展生存更长。NDB患者拷贝数改变基因比例最高。EGFR和STK11改变与缺少获益有关。TMB和PD-L1表达是独立变量,TMB和PD-L1组合进一步增加ICI的临床获益。

【5】Nivolumab治疗晚期非小细胞肺癌的5年随访结果

在两项Ⅲ期临床试验中,Nivolumab,一种PD-1抑制剂抗体,与多西他赛相比可以改善进行过治疗的晚期非小细胞肺癌患者的总生存率。近期一项研究报道了Nivolumab治疗这类人群的5年随访结果并描述5年生存患者的特征。结果表明,所有患者5年总生存率为16%。鳞状细胞和非鳞状细胞非小细胞肺癌患者的5年总生存率相似。10例可以评估PD-L1表达的5年生存患者中,70%基线PD-L1表达≥1%。12例5年生存患者接受Nivolumab治疗后达到了部分缓解,2例病情稳定。9例5年生存患者完成了最高的96周期Nivolumab治疗,4例由于不良反应中断治疗,3例由于疾病进展中断治疗。在2016年11月数据库截止时,12例5年生存患者未接受其他治疗且在最后随访时也没有疾病进展的证据。


【6】ALT-803(IL-15强激动剂)联合nivolumab用于转移性非小细胞肺癌安全性可耐受

利用PD-1或PD-L1阻滞的免疫疗法用于未选择的非小细胞肺癌(NSCLC)时,高达80%的患者无反应,且其中好多患者在治疗初期会对治疗产生抗药性。靶向IL-2和IL-15Rβγ共享通路的药物可诱导某些癌症获得完全缓解和持久性反应,但尚无研究对这些药物与抗PD-1免疫疗法联合治疗的安全性或疗效进行评估。近日一项非随机的开放性Ib期试验研究对该药物联合疗法用于NSCLC患者的安全性、耐受性和活性进行评估。研究人员从USA的三家医院招募年满18岁的既往治疗过的组织学或细胞学确诊的IIIB或IV期NSCLC患者。予以抗PR-1单克隆抗体nivolumab 静脉 3mg/kg(后改为240mg)14天一疗程和IL-15强激动剂ALT-803 皮下用药 1/周(1-5周)6周一疗程,共4个疗程持续6个月。结果表明,ALT-803联合nivolumab用于门诊患者安全性可接受。采用PD-1单克隆抗体治疗的复发性或难治性疾病患者,补充ALT-803治疗后的临床活性,提示ALT-803联合nivolumab或许可成为NSCLC患者的新的可有效抗肿瘤的治疗方案。

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    学习

    0

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    2018-04-15 weiwei412720_57191401

    个性化医疗.是否能被推向新的日程

    0

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    2018-04-13 hanmeijinxiu

    学习了.谢谢分享!

    0

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    2018-04-12 清风拂面

    谢谢分享学习

    0

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    2018-04-12 wqkm

    ^_^^_^^_^

    0