Clin Cancer Res:瑞普替尼在携带KIT/PDGFRA突变的晚期胃肠道间质瘤患者中的显著疗效

2021-10-24 Nebula MedSci原创

瑞普替尼在晚期 GIST 患者的突变亚组中提供了具有临床意义的治疗活性

大多数胃肠道间质瘤 (GIST) 患者携带KIT/PDGFRA基因激活突变,并且最初对酪氨酸激酶抑制剂 (TKI) 治疗有反应。继发性突变的获得导致难治性/复发性疾病。3期INVICTUS 研究表征了晚期 GIST 患者肿瘤的基因组异质性,并评估了瑞普替尼(Ripretinib)在携带 KIT/PDGFRA 突变的患者亚组中的疗效。

在该研究中,研究人员收集了受试患者的肿瘤组织和液体活检样本,提取了循环肿瘤 DNA,进行了二代测序。本文旨在分析 KIT/PDGFRA 突变状态与患者临床结果的相关性。

突变检出情况

总体上,共招募了129位患者(85位服用瑞普替尼 150 mg/日;44位服用安慰剂)。肿瘤组织和液体活检样本联合检测到的最常见的原发突变位于 KIT 的第11号外显子(瑞普替尼组 61.2%,安慰剂组 77.3%)和 KIT 的第9号外显子(瑞普替尼组 18.8%,安慰剂组 15.9%)。

根据突变状态分层的两组患者的无进展生存期

无论受试患者的突变状态如何,接受瑞普替尼治疗的患者的无进展生存期(PFS)获益都优于安慰剂组(HR 0.16;11号外显子突变 p<0.0001,9号外显子突变 p=0.0023, 13号外显子突变 p<0.0001, 17号外显子突变 p<0.0001)。在没有 KIT/PDGFRA 突变(野生型)的患者中,瑞普替尼组和安慰剂组患者的PFS分别波动在2-23个月和0.9-10.1个月。

综上所述,瑞普替尼在晚期 GIST 患者的突变亚组中提供了具有临床意义的治疗活性,证明了瑞普替尼可抑制既往接受过三种或更多种 TKI 治疗有广泛 KIT/PDGFRA 突变的晚期 GIST 患者

原始出处:

Sebastian Bauer, et al. Clinical Activity of Ripretinib in Patients with Advanced Gastrointestinal Stromal Tumor Harboring Heterogeneous KIT/PDGFRA Mutations in the Phase III INVICTUS Study. Clin Cancer Res October 20 2021 DOI:10.1158/1078-0432.CCR-21-1864

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    2021-10-26 liuyiping
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    2021-10-26 shuangle
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    2021-10-24 ms9000000212834100

    大多数胃肠道间质瘤 (GIST) 患者携带KIT/PDGFRA基因激活突变,

    0

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予以局限性GIST患者新辅助系统疗法与适度的生存益处和较低的术后90天死亡率相关,且不影响R0切除的可能性。