Clin Cancer Res:采用卡博替尼单药治疗晚期软组织肉瘤

2022-01-27 Nebula MedSci原创

卡博替尼单药在特定亚型的软组织肉瘤中具有抗肿瘤活性

软组织肉瘤 (STS) 是一种罕见的异质性的间质肿瘤。几十年来,不可切除的晚期 STS 的主要治疗方法是姑息性化疗。在各种肉瘤细胞系中均报道了高水平的活化的 MET 受体,再加上 STS 患者的血管内皮生长因子 (VEGF) 水平升高,提示采用多受体酪氨酸激酶抑制剂卡博替尼双重靶向 VEGF 和 MET 通路将在该人群中产生临床益处。

研究人员开展了一项开放标签、多机构、单臂的 II 期单卡博替尼治疗的临床试验,受试患者是至少接受过一次标准系统治疗的侵袭性晚期 STS。予以受试者卡博替尼 60mg 口服,1次/日,28天为一疗程。主要终点是总缓解率和6个月无进展生存期(PFS)。次要终点是几种循环生物标志物的变化。

可评估患者的最佳反应

中位治疗疗程为 4 个(范围 1-99)。在 54 位可评估患者中,有 6 位(11.1%)患者获得了客观缓解(全部为部分缓解)。6 个月 PFS 为 49.3%(95% CI 36.2%-67.3%)

无进展生存期

最常见的 3-4 级副反应有高血压(7.4%)和中性粒细胞减少(16.7%)。在一个治疗疗程后,患者的循环肝细胞生长因子 (HGF)、可溶性 MET 和 VEGF-A 水平普遍升高,但可溶性 VEGFR2 水平降低了,且无论临床预后如何。

副反应

综上所述,在特定组织学亚型(肺泡软肉瘤、未分化多形性肉瘤、骨骼外粘液样软骨肉瘤和平滑肌肉瘤)的 STS 患者中,卡博替尼单药展现出了一定的抗肿瘤活性,强调了 STS 的生物分子多样性。

原始出处:

Geraldine O'Sullivan Coyne, et al. Clinical Activity of Single-Agent Cabozantinib (XL184), a Multi-receptor Tyrosine Kinase Inhibitor, in Patients with Refractory Soft-Tissue Sarcomas. Clin Cancer Res January 15 2022 28 (2) 279-288; DOI:10.1158/1078-0432.CCR-21-2480

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