Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Abdominal Imaging, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Oncologist. 2021 Jun;26(6):476-482. doi: 10.1002/onco.13770. Epub 2021 Apr 21.
Lenvatinib (Len) plus everolimus (Eve) is an approved therapy for metastatic renal cell carcinoma (mRCC) after first-line vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs), but limited data exist on the efficacy of Len ± Eve after progression on immune checkpoint inhibitors (ICIs) and VEGFR-TKIs.
We retrospectively reviewed the records of patients with mRCC at our institution who were treated with Len ± Eve after ICI and VEGFR-TKI. A blinded radiologist assessed objective response as defined by RECIST version 1.1. Descriptive statistics and the Kaplan-Meier method were used.
Fifty-five patients were included in the analysis. Of these patients, 81.8% had clear-cell histology (ccRCC), and 76.4% had International Metastatic RCC Database Consortium intermediate-risk disease. Median number of prior therapies was four (range, 2-10); all patients had prior ICIs and VEGFR-TKIs, and 80% were previously treated with ICI and at least two VEGFR-TKIs, including cabozantinib. One patient (1.8%) achieved a complete response, and 11 patients (20.0%) achieved a partial response, for an overall response rate (ORR) of 21.8%; 35 patients (63.6%) achieved stable disease. In all patients, median progression-free survival (PFS) was 6.2 months (95% confidence interval [CI], 4.8-9.4) and median overall survival (OS) was 12.1 months (95% CI, 8.8-16.0). In patients with ccRCC, ORR was 24.4%, PFS was 7.1 months (95% CI, 5.0-10.5), and OS was 11.7 months (95% CI, 7.9-16.1). 50.9% of patients required dose reductions and 7.3% discontinued treatment because of toxicity.
Len ± Eve demonstrated meaningful clinical activity and tolerability in heavily pretreated patients with mRCC after disease progression with prior ICIs and VEGFR-TKIs.
As the therapeutic landscape for patients with metastatic renal cell carcinoma continues to evolve, this single-center, retrospective review highlights the real-world efficacy of lenvatinib with or without everolimus in heavily pretreated patients. This article supports the use of lenvatinib with or without everolimus as a viable salvage strategy for patients whose disease progresses after treatment with immune checkpoint inhibitors and vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies, including cabozantinib.
仑伐替尼（Len）联合依维莫司（Eve）是一线血管内皮生长因子受体酪氨酸激酶抑制剂（VEGFR-TKIs）治疗转移性肾细胞癌（mRCC）后的一种获批疗法，但在免疫检查点抑制剂（ICIs）和 VEGFR-TKIs 进展后，仑伐替尼 ± 依维莫司的疗效数据有限。
我们对在我院接受 ICI 和 VEGFR-TKI 后接受仑伐替尼 ± 依维莫司治疗的 mRCC 患者的记录进行了回顾性分析。一位盲法放射科医生根据 RECIST 版本 1.1 评估了客观缓解。采用描述性统计和 Kaplan-Meier 方法。
55 例患者纳入分析。这些患者中，81.8%为透明细胞组织学（ccRCC），76.4%为国际转移性肾细胞癌数据库联盟中危疾病。中位治疗前治疗次数为 4 次（范围，2-10）；所有患者均接受过 ICIs 和 VEGFR-TKIs 治疗，80%的患者既往接受过 ICI 和至少两种 VEGFR-TKIs 治疗，包括卡博替尼。1 例患者（1.8%）达到完全缓解，11 例患者（20.0%）达到部分缓解，总缓解率（ORR）为 21.8%；35 例患者（63.6%）疾病稳定。所有患者的中位无进展生存期（PFS）为 6.2 个月（95%置信区间[CI]，4.8-9.4），中位总生存期（OS）为 12.1 个月（95%CI，8.8-16.0）。在 ccRCC 患者中，ORR 为 24.4%，PFS 为 7.1 个月（95%CI，5.0-10.5），OS 为 11.7 个月（95%CI，7.9-16.1）。50.9%的患者需要减少剂量，7.3%的患者因毒性而停止治疗。
仑伐替尼 ± 依维莫司在既往接受 ICIs 和 VEGFR-TKIs 治疗后疾病进展的 mRCC 患者中显示出有意义的临床活性和可耐受性。
随着转移性肾细胞癌患者的治疗前景不断发展，这项单中心回顾性研究强调了仑伐替尼联合或不联合依维莫司在大量预处理患者中的真实疗效。本文支持将仑伐替尼联合或不联合依维莫司作为免疫检查点抑制剂和血管内皮生长因子受体酪氨酸激酶抑制剂治疗后疾病进展患者的可行挽救策略，包括卡博替尼。
