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2期试验

原文发布日期：2025-02-27

英文摘要：

摘要翻译：

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2期试验

a phase 2 trial

原文发布日期：2025-02-27

英文摘要：

Cabozantinib is an oral multikinase inhibitor approved for treatment in metastatic renal cell carcinoma (RCC). We conducted a phase 2, nonrandomized, single-arm clinical trial (NCT04022343) of cabozantinib treatment for 12 weeks in 17 patients with locally advanced, biopsy-proven, nonmetastatic clear cell RCC before surgical resection. The primary end point was the objective response rate (complete and partial responses) at week 12 and secondary end points included safety, tolerability, clinical and surgical outcomes, and quality of life. Six patients (35%) experienced a partial response and 11 patients (65%) had stable disease. The most common adverse events were diarrhea (n = 12, 70.6%), anorexia, fatigue and hypertension (n = 10, 58.8%), nausea and palmar-plantar erythrodysesthesia syndrome (n = 9, 52.9%). No treatment grade 4 or 5 adverse events related to cabozantinib or surgery occurred. The 1-year disease-free survival and overall survival were 82.4% (95% CI 54.7–93.9%) and 94.1% (95% CI 65–99.1%), respectively. Cabozantinib treatment activated CD8+ T cells in the blood, depleted myeloid populations and induced immune niches for TCF1+ stem-like CD8+ T cells. Cabozantinib was clinically active and safe in the neoadjuvant setting in patients with locally advanced nonmetastatic clear cell RCC.

摘要翻译：

cabozantinib是一种口服多激酶抑制剂，已获准用于治疗转移性肾细胞癌（RCC）。我们开展了一项II期、非随机化、单臂临床试验（NCT04022343），评估了cabozantinib在17名经组织学证实的基底细胞癌患者中的疗效，这些患者有局部晚期症状但尚未手术切除。主要终点是12周时的客观缓解率（完全反应和部分反应），次要终点包括安全性、耐受性、临床效果、外科效果及生活质量。研究结果显示，35%的患者发生部分缓解，65%的患者病情稳定。最常见的不良事件包括腹泻（n=12, 70.6%）、厌食、疲劳和高血压（n=10, 58.8%）、恶心和手掌-脚板综合征（n=9, 52.9%）。未发生与cabozantinib或手术相关的4级或5级不良事件。1年后无病生存率和总生存率分别为82.4%（95%CI 54.7–93.9%）和94.1%（95%CI 65–99.1%）。cabozantinib治疗激活了血浆中的CD8+ T细胞，减少了髓系人群，并诱导了TCF1+干细胞型CD8+ T细胞的免疫微环境。在局部晚期基底细胞癌患者的新辅助 setting中，cabozantinib显示出临床活性和安全性。