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

• Published in: The oncologist (Dayton, Ohio) Vol. 26; no. 6; pp. 476 - 482
• Main Authors: Wiele, Andrew J., Bathala, Tharakeswara K., Hahn, Andrew W., Xiao, Lianchun, Duran, Munevver, Ross, Jeremy A., Jonasch, Eric, Shah, Amishi Y., Campbell, Matthew T., Msaouel, Pavlos, Tannir, Nizar M.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.06.2021; Oxford University Press
• Subjects: Analysis; Antimitotic agents; Antineoplastic agents; Cabozantinib; Carcinoma, Renal cell; Carcinoma, Renal Cell - drug therapy; Care and treatment; Complications and side effects; Diagnosis; Drug therapy; Everolimus - therapeutic use; Genitourinary Cancer; Humans; Immune Checkpoint Inhibitors; Kidney Neoplasms - drug therapy; Lenvatinib; Lenvatinib plus everolimus; Metastasis; Patient outcomes; Pharmaceutical industry; Phenols; Phenylurea Compounds; Protein Kinase Inhibitors - therapeutic use; Quinolines; Receptors, Vascular Endothelial Growth Factor - therapeutic use; Renal cell carcinoma; Retrospective Studies; Tyrosine; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A; United States; Cabozantinib; Immune checkpoint inhibitors; Lenvatinib; Lenvatinib plus everolimus; Renal cell carcinoma
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1002/onco.13770

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 ± 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 ± 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 ± Eve demonstrated meaningful clinical activity and tolerability in heavily pretreated patients with mRCC after disease progression with prior ICIs and VEGFR‐TKIs. 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. This article reports on the efficacy and safety of lenvatinib alone or in combination with everolimus in patients with clear‐cell and non–clear‐cell metastatic renal cell carcinoma who previously received immune checkpoint inhibitor and VEGFR‐TKI therapies.