尽管转移性肾细胞癌（mRCC）有了更多的治疗选择，但大多数患者最终都会出现疾病进展。在难治性情况下，重新尝试可能是一种令人信服的策略。卡博替尼在一线和后续治疗中是常规治疗，但其在重新尝试治疗中的活性尚不清楚。本回顾性研究评估了卡博替尼重新尝试治疗的疗效和安全性，定义为停药≥3个月或≥1种其他治疗后再次接受治疗的情况下的第二次治疗。主要终点是重新尝试治疗的中位进展无进展生存期（PFS）。次要终点包括总生存期、客观缓解率和重新尝试治疗的安全性。在2017年至2022年间，我们纳入了51例接受卡博替尼重新尝试治疗的mRCC患者。诊断时的中位年龄为54岁，78%为男性，90%为清细胞型mRCC，92%曾进行过肾切除术。15例（29%）在治疗中间停药后重新接受治疗，而36例（70.6%）在第一次卡博替尼暴露（CABO-1）和重新尝试（CABO-2）之间有≥1种其他治疗方法。CABO-1的中位PFS为15.1个月（mo，95%置信区间为11.2-22.1），而CABO-2为14.4个月（95%CI为9.8-NR）。CABO-1的中位总生存期为67.6个月（95% CI为52.2-NR），而CABO-2为27.4个月（95%CI为17.2-NR）；CABO-1的客观缓解率为70.6%，而CABO-2为60%。CABO-2的PFS在CABO-1的PFS>12个月的患者以及因毒性停药的患者中较高，但无统计学意义。没有出现意外的不良事件。卡博替尼的重新尝试是一种可行的治疗选择，对mRCC患者可能有潜在的临床益处。版权所有©2023 Elsevier Ltd.保留所有权利。

Despite metastatic renal cell carcinoma (mRCC) expanded treatment options, disease progression ultimately occurs for most patients. Rechallenge may be a compelling strategy in a refractory setting. Cabozantinib is the standard of care in first and later lines of therapy, but its activity in rechallenge is unknown.This retrospective study assessed the efficacy and safety of cabozantinib rechallenge, as defined by a second exposure after an interval of ≥3 months without treatment or ≥1 other treatment line, in patients with mRCC. The primary endpoint was median progression-free survival (PFS) at rechallenge. Secondary endpoints included overall survival, objective response rate, and safety at rechallenge.We included 51 mRCC patients who received cabozantinib in a rechallenge setting between 2017 and 2022. Median age at diagnosis was 54 years, 78% were male, 90% had clear cell mRCC, and 92% had prior nephrectomy. 15 patients (29%) were rechallenged after a pause in treatment, whereas 36 (70.6%) had ≥1 other treatment lines between first cabozantinib exposure (CABO-1) and rechallenge (CABO-2). Median PFS was 15.1 months (mo, 95% Confidence interval 11.2-22.1) at CABO-1 and 14.4mo (95%CI 9.8-NR) at CABO-2. Median overall survival was 67.6mo for CABO-1 (95% CI 52.2-NR) and 27.4mo for CABO-2 (95%CI 17.2-NR); objective response rate was 70.6% for CABO-1 and 60% for CABO-2. CABO-2 PFS was higher for patients with CABO-1 PFS > 12 months, and for those who discontinued CABO-1 because of toxicity, without statistical significance. There were no unexpected adverse events.Cabozantinib rechallenge is a feasible treatment option with potential clinical benefit for mRCC patients.Copyright © 2023 Elsevier Ltd. All rights reserved.