Bilen Mehmet A, Vo BaoHan T, Liu Yuan, Greenwald Rachel, Davarpanah Amir H, McGuire Donald, Shiradkar Rakesh, Li Liping, Midya Adhishek, Nazha Bassel, Brown Jacqueline T, Williams Sierra, Session Wilena, Russler Greta, Caulfield Sarah, Joshi Shreyas S, Narayan Vikram M, Filson Christopher P, Ogan Kenneth, Kucuk Omer, Carthon Bradley Curtis, Del Balzo Luke, Cohen Athena, Boyanton Adriana, Prokhnevska Nataliya, Cardenas Maria Andrea, Sobierajska Ewelina, Jansen Caroline S, Patil Dattatraya H, Nicaise Edouard, Osunkoya Adeboye O, Kissick Haydn T, Master Viraj A
Winship Cancer Institute of Emory University, Atlanta, GA, USA.
Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.
Nat Cancer. 2025 Mar;6(3):432-444. doi: 10.1038/s43018-025-00922-5. Epub 2025 Feb 27.
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.
卡博替尼是一种口服多激酶抑制剂，已被批准用于治疗转移性肾细胞癌（RCC）。我们进行了一项2期非随机单臂临床试验（NCT04022343），对17例经活检证实为局部晚期、非转移性透明细胞RCC患者在手术切除前给予卡博替尼治疗12周。主要终点是第12周时的客观缓解率（完全缓解和部分缓解），次要终点包括安全性、耐受性、临床和手术结果以及生活质量。6例患者（35%）出现部分缓解，11例患者（65%）疾病稳定。最常见的不良事件是腹泻（n = 12，70.6%）、厌食、疲劳和高血压（n = 10，58.8%）、恶心和手足红斑感觉异常综合征（n = 9，52.9%）。未发生与卡博替尼或手术相关的4级或5级治疗不良事件。1年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%）。卡博替尼治疗激活了血液中的CD8 T细胞，消耗了髓系细胞群，并诱导了TCF1干细胞样CD8 T细胞的免疫微环境。在局部晚期非转移性透明细胞RCC患者的新辅助治疗中，卡博替尼具有临床活性且安全。
