Clini Cancer Research:二代ROS1-TKI,repotrectinib,治疗初治或ROS1突变的NSCLC

2020-07-04 QQY MedSci原创

目的:虽然一线克唑替尼治疗使ROS1+肺癌患者获益,但高克唑替尼耐药性ROS1-G2032R (ROS1G2032R)突变发生率和中枢神经系统(CNS)进展给肺癌治疗带来挑战。本研究拟评估一种新型二代

目的:虽然一线克唑替尼治疗使ROS1+肺癌患者获益,但高克唑替尼耐药性ROS1-G2032R (ROS1G2032R)突变发生率和中枢神经系统(CNS)进展给肺癌治疗带来挑战。本研究拟评估一种新型二代ROS1/TRK/ALK酪氨酸激酶抑制剂(TKI)repotrectinib用于ROS1+患者来源的临床前模型的抗肿瘤活性。

设计:在ROS1+突变患者来源的临床前模型(包括初治和ROS1G2032R模型)中评估repotrectinib的抗肿瘤活性,并进一步在一个正在进行的I/II期临床试验(NCT03093116)招募的患者中进行验证。在脑转移小鼠模型中评估repotrectinib的颅内抗肿瘤活性。

结果:与已应用于临床可用的克唑替尼、色瑞替尼和恩曲替尼相比,repotrectinib能有效地抑制初治YU1078模型的体内外肿瘤生长和ROS1下游信号。虽然repotrectinib和劳拉替尼在YU1078来源的异种移植模型中的肿瘤回归具有可比性,但repotrectinib明显延迟了停药后的肿瘤复发。此外,repotrectinib可有效的穿过血脑屏障,在CNS中发挥显著的抗肿瘤活性。值得注意的是,repotrectinib在体外和体内对ROS1G2032R突变均表现出选择性的强效活性。这些结果在正在进行的I/II期临床试验中得到了验证。

结论:Repotrectinib是一种新一代的ROS1-TKI,对初治和ROS1G2032R突变的肺癌具有较好的抗肿瘤活性和选择性,并能有效地穿透血脑屏障。本研究结果提示repotrectinib可有效用作NSCLC的一线疗法和已有ROS1-TKI治疗后进展的挽救疗法。

原始出处:

Mi Ran Yun,et al. Repotrectinib Exhibits Potent Antitumor Activity in Treatment-Naive and Solvent-Front–Mutant ROS1-Rearranged Non–Small Cell Lung Cancer. Clinical Cancer Research. DOI: 10.1158/1078-0432.CCR-19-2777 Published July 2020

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    2020-07-06 lsndxfj
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    2020-07-06 lsj628
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    2020-07-06 jichang
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    2020-07-04 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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