The efficacy of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma exhibiting primary resistance to front-line targeted therapy or immunotherapy

Hamieh, Lana; Beck, R. L.; Le, Viet Ha; Hsieh, Jan-Sing

doi:10.17650/1726-9776-2020-16-3-53-61

Cited by 2 publications

(2 citation statements)

References 23 publications

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“…In the three‐arm, randomized, phase II, registration trial (Study 205), 51 patients with mRCC received lenvatinib plus everolimus [14]. Besides a case series of seven patients, there are no real‐world data on the efficacy or safety of lenvatinib plus everolimus for patients with ccRCC or nccRCC [28]. Our cohort included 42 patients who received lenvatinib plus everolimus and 13 patients who received lenvatinib alone, making it one of the largest real‐world experiences using lenvatinib for ccRCC and nccRCC.…”

Section: Discussionmentioning

confidence: 99%

Lenvatinib with or Without Everolimus in Patients with Metastatic Renal Cell Carcinoma After Immune Checkpoint Inhibitors and Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitor Therapies

et al. 2021

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Introduction. 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 AE Eve after progression on immune checkpoint inhibitors (ICIs) and VEGFR-TKIs. Methods. We retrospectively reviewed the records of patients with mRCC at our institution who were treated with Len AE 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. Results. 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. Conclusion.Len AE Eve demonstrated meaningful clinical activity and tolerability in heavily pretreated patients with mRCC after disease progression with prior ICIs and VEGFR-TKIs. The Oncologist 2021;26:1-7 Implications for Practice: 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.

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Section: Discussionmentioning

confidence: 99%

Lenvatinib with or Without Everolimus in Patients with Metastatic Renal Cell Carcinoma After Immune Checkpoint Inhibitors and Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitor Therapies

et al. 2021

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“…The clinical efficacy of Lenvatinib is well established now and has been found to extend HCC patient survival by 13.6 months, while for Sorafenib this was 12.3 months [8,11]. This modest survival benefit may, however, be lost due to drug resistance, as has been observed for Sorafenib [12]. Lenvatinib primarily affects angiogenesis, and additional studies implied that orally administered Lenvatinib exhibited anti-angiogenic activity in thyroid cancer, lung cancer and HCC [8,10,13].…”

Section: Introductionmentioning

confidence: 93%

MT1JP-mediated miR-24-3p/BCL2L2 axis promotes Lenvatinib resistance in hepatocellular carcinoma cells by inhibiting apoptosis

Takata

et al. 2021

Cell Oncol.

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Purpose Lenvatinib is a long-awaited alternative to Sorafenib for first-line targeted therapy of patients with advanced hepatocellular carcinoma (HCC). However, resistance to Lenvatinib results in tumor progression and has become a major obstacle to improving the prognosis of HCC patients. Exploring the mechanisms underlying Lenvatinib resistance is considered essential for the treatment of advanced HCC. Methods Lenvatinib resistant HCC (LR-HCC) cells were generated and potential long non-coding RNAs (Lnc-RNAs) upregulated in LR-HCC cells were identified by RNA sequencing. The effects of upregulated Lnc-RNAs were evaluated in vitro in cell models and in vivo in experimental animals using quantitative cell viability and apoptosis assays. Results We found that Lnc-RNA MT1JP (MT1JP) was upregulated in LR-HCC cells and inhibited the apoptosis signaling pathway. In addition, we found that sponging of microRNA-24-3p by MT1JP released Bcl-2 like 2 (BCL2L2), an anti-apoptotic protein, thereby forming a positive-feedback loop. The role of this feedback loop was validated using rescue assays. Additionally, we found that upregulation of MT1JP and BCL2L2 impaired the sensitivity of HCC cells to Lenvatinib both vitro and vivo. Conclusions Our results suggest a novel molecular feedback loop between MT1JP and apoptosis signaling in Lenvatinib sensitive HCC cells.

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The efficacy of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma exhibiting primary resistance to front-line targeted therapy or immunotherapy

Cited by 2 publications

References 23 publications

Lenvatinib with or Without Everolimus in Patients with Metastatic Renal Cell Carcinoma After Immune Checkpoint Inhibitors and Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitor Therapies

Lenvatinib with or Without Everolimus in Patients with Metastatic Renal Cell Carcinoma After Immune Checkpoint Inhibitors and Vascular Endothelial Growth Factor Receptor-Tyrosine Kinase Inhibitor Therapies

MT1JP-mediated miR-24-3p/BCL2L2 axis promotes Lenvatinib resistance in hepatocellular carcinoma cells by inhibiting apoptosis

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