AACR 2020:波奇替尼治疗NSCLC的EGFR 20ins的II期研究

2020-04-29 MedSci MedSci原创

EGFR突变是非小细胞肺癌中最常见的靶点,不过同样是EGFR突变,为何部分患者靶向治疗的效果更差或者很快耐药。其中一项重要的原因就是EGFR上还存在一些罕见突变,比如20ins、G719x、L861Q

EGFR突变是非小细胞肺癌中最常见的靶点,不过同样是EGFR突变,为何部分患者靶向治疗的效果更差或者很快耐药。其中一项重要的原因就是EGFR上还存在一些罕见突变,比如20ins、G719x、L861Q和S768I等等。一代EGFR TKI药物已然无法满足这类患者的需要,这类罕见难治的EGFR突变还能用哪些靶向药?

Poziotinib(波奇替尼)是一种针对罕见EGFR和HER2外显子20插入突变的新型靶向药,ZENITH20 Ⅱ期试验正在评估波奇替尼单药治疗20ins的疗效,试验招募EGFR(n=50) 或 HER2 20ins(n=13)非小细胞肺癌患者,每日口服16mg波奇替尼,EGFR组和HER2组的大多数患者既往接受过铂类化疗(86%和77%)、TKI治疗(34%和15%)或PD-1/PD-L1治疗(54%和62%)。

EGFR组的44例可评估患者中,ORR为55%,经确认的ORR为43%,意向治疗人群的中位无进展生存期为5.5个月,数据截止时仍有19例患者在接受治疗,其中6例患者治疗时间超过1年。HER2组的12例可评估患者中,ORR为50%,经确认的ORR为42%,中位PFS为5.1个月,5例患者仍在接受治疗。这项研究中,波奇替尼治疗EGFR 20ins的ORR创历史新高。安全性上,最常见的全等级不良反应包括腹泻(69.8%)、口腔黏膜炎(69.8%)、甲沟炎(60.3%)和皮肤干燥(58.7%),安全可控。

此次共报告115例EGFR 20ins的晚期NSCLC患者的数据。

波奇替尼为20插入突变(ins)的靶向药物。既往有消息报道该药在II期研究中未达到预设的主要研究终点,一起看看研究数据。该II期研究共纳入了115例EGFR 20ins的晚期NSCLC患者,这些患者都属于标准治疗失败(主要是化疗和免疫)。既往中位治疗线数为2。

结果显示,ORR为14.8%,DCR为68.7%,错失了预设的主要研究终点(ORR的95%CI下限>17%)17例患者达到确认的PR,5例患者为未确认PR,53.9%患者为SD。总共有65%患者出现肿瘤缩小。中位DOR为7.4个月,中位PFS为4.2个月。

虽然ORR未达到预设终点,但是波奇替尼在大部分患者中(65%)都成功缩小了肿瘤,并且疗效也较持久。

不过,2019WCLC公布了一项奥希替尼联合耐昔妥珠单抗治疗EGFR 20ins的Ⅰ期扩展队列结果,最终4例患者可评估疗效,2例患者部分缓解,ORR为50%,中位PFS为5.3个月。

来自中山大学肺癌研究中心的张力教授团队分析了奥希替尼治疗EGFR 20 ins患者疗效的回顾性研究。研究中有6例EGFR 20-ins的NSCLC患者接受奥希替尼治疗,都是晚期肺腺癌患者,主要是女性(5/6),中位年龄为64岁。其中4例患者出现肺和胸膜的转移。患者5为脑转移,患者6为骨转移。两例患者接受奥希替尼一线治疗,其他都是≥2线治疗,且其中两例患者在奥希替尼治疗前接受过其他EGFR TKI治疗。中位随访时间为6.2个月。四例(67.7%)患者获得部分缓解(PR),两例患者(33.3%)获得稳定疾病(SD),疾病控制率100%。

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    2021-04-04 tamgche
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    2020-05-01 10518094zz
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    2020-05-01 liuyiping
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    2020-05-01 Luyuxie_14
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    2020-04-29 肿肿

    NSCLC下一步突破在于新靶点了,靶向治疗和免疫治疗基本见顶了,再有新的就需要新机制了

    0

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AACR重磅:局部晚期或转移性胃/GEJ癌患者使用抗TTX-030联合化学免疫疗法的一线治疗的安全性有效性评估

TTX-030、布加利单抗和FOLFOX的组合作为1L治疗LA/M胃/GEJ癌,无论CPS状态如何,都表现出良好的疗效

AACR重磅之KEYNOTE-042:帕博丽珠单抗持续延长了中国晚期/转移性PD-L1阳性NSCLC患者的生存期——Keynote-042中国研究的4年随访数据结果

一线帕博丽珠单抗继续延长了中国晚期/转移性PD-L1阳性NSCLC患者的OS,并在随访近4年后提供了持久的反应。

AACR重磅:高基因扩增和肿瘤突变负荷组合作为接受替雷丽珠单抗治疗患者的泛癌生物标志物

TMB和HA的组合对用替雷利珠单抗治疗各种实体瘤类型的临床获益有预测作用。

AACR重磅之RATIONALE-304:肿瘤突变负荷(TMB)与替雷利珠单抗(TIS)+化疗(chemo)与单独化疗在晚期非鳞状非小细胞肺癌(nsq-NSCLC)一线治疗的临床结局研究

tTMB和bTMB都没有与PFS获益显著相关,表明在TIS+化疗作为晚期nsq-NSCLC一线治疗的情况下,tTMB和bTMB的临床效用有限。