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Clin Cancer Res:FGFR抑制剂Infigratinib单药治疗携带EGFR变异的复发性胶质瘤的疗效

2022-04-05 Nebula MedSci原创

携带 FGFR1 或 FGFR3 点突变以及 FGFR3-TACC3 融合变异的患者可从 Infigratinib 单药治疗中获得持久的疾病控制

神经胶质瘤是一种临床表现多样的原发性脑肿瘤,全世界每年约有10 万人被诊断为胶质瘤。胶质母细胞瘤是最常见的原发性脑肿瘤类型,其侵袭性特别强,标准治疗后的中位总生存期 (OS) 约只有 15-18 个月。约 8% 的神经胶质瘤携带成纤维细胞生长因子受体 (FGFR) 基因组变异(扩增、突变和/或融合),特别是 EGFR1 和 EGFR2。

本研究是一项多中心、开放标签、单臂的II期研究,评估了选择性EGFR1-3抑制剂 Infigratinib(BGJ398)在携带 EGFR 变异的复发性神经胶质瘤中的有效性和安全性。

招募了明确携带 EGFR 变异的复发性或进展的神经胶质瘤成年患者,予以口服 Infigratinib 125 mg(1-21/28天)。主要终点是调查者评估的 6 个月无进展生存率(PFS)。此外,研究人员还对预处理的肿瘤组织进行了全面的基因组谱分析,以探索其他与疗效相关的分子特征。


治疗效果

共招募了 26 位患者,6 个月无进展生存率为 16%,中位无进展生存期是 1.7 个月,客观缓解率为 3.8%。但是,4 位患者获得了持久的病情控制(至少 1 年):其中 3 位患者携带 FGFR1(K656E)[n=2]或 EGFR3(K650E)[n=1] 激活性点突变,而一位患者携带 FGFR3-TACC3 融合变异。高磷血症是最常见的治疗相关不良事件 (全级发生率:76.9%; 3级发生率:3.8%),是一种已知的 FGFR 抑制剂的靶内毒性。


最常见的治疗相关的不良反应

综上,FGFR 抑制剂 Infigratinib 单药治疗在携带 EGFR 变异的复发性神经胶质瘤患者中的疗效有限,但携带 FGFR1 或 FGFR3 点突变以及 FGFR3-TACC3 融合变异的患者可从 Infigratinib 单药治疗中获得持久的疾病控制

 

原始出处:

Lassman Andrew B,Sepúlveda-Sánchez Juan Manuel,Cloughesy Timothy et al. Infigratinib in Patients with Recurrent Gliomas and FGFR Alterations: A Multicenter Phase II Study.[J] .Clin Cancer Res, 2022, https://doi.org/10.1158/1078-0432.CCR-21-2664.

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    2022-12-14 zhouqu_8
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    2022-04-11 jklm09
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    2022-04-05 130a765fm69暂无昵称

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    2022-04-05 1251df21m40暂无昵称

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  9. 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