Clinical Activity of Lenvatinib with or without Everolimus in Heavily Pretreated Disease

2021 Year in Review - Renal-Cell Carcinoma

Lenvatinib is a tyrosine kinase inhibitor that is approved for use in combination with the mammalian target of rapamycin inhibitor everolimus for patients with advanced renal-cell carcinoma (RCC) that has been previously treated with an antiangiogenic therapy. However, the standard of care for advanced RCC in the frontline setting is increasingly including immune checkpoint inhibition. Data regarding the effectiveness of lenvatinib alone or in combination with everolimus after immunotherapy have not previously been reported. In this retrospective study conducted at The University of Texas MD Anderson Cancer Center, Houston, consecutive patients with metastatic RCC who received lenvatinib with or without everolimus between November 2016 and February 2020 were enrolled.1

A total of 55 patients received lenvatinib plus everolimus (76.4%) or lenvatinib alone (23.6%). Of these, 45 patients had clear-cell RCC and 10 patients had non–clear-cell RCC. This was a heavily pretreated patient population: patients had received a median of 4 previous lines of therapy (range, 2-10). Lenvatinib was administered as fourth-line treatment in 40% of patients, fifth-line treatment in 20% of patients, sixth-line treatment in 16.4% of patients, and seventh-line or later in 16.4% of patients. Before receipt of treatment with lenvatinib with or without everolimus, all patients had received an immune checkpoint inhibitor, and 80% had received an immune checkpoint inhibitor in addition to at least 2 tyrosine kinase inhibitors.1

From time of initiation of lenvatinib, median progression-free survival was 6.2 months (95% confidence interval [CI], 4.8-9.4). In patients with clear-cell RCC, median progression-free survival was 7.1 months (95% CI, 5.0-10.5) compared with 3.2 months for those with non–clear-cell RCC (95% CI, 3.1-not achieved). For all patients, median overall survival was 12.1 months (95% CI, 8.8-16.0). In those with clear-cell RCC, median overall survival was 11.7 months (95% CI, 7.9-16.1) compared with 12.5 months for those with non–clear-cell RCC (95% CI, 4.3-not achieved).1

Across all patients, confirmed overall response rate was 21.8%. One patient achieved a complete response. Overall response rate for clear-cell RCC was 24.4% and for non–clear-cell RCC was 10.0%.1

The most common grade 3 adverse events were proteinuria (18.2%), diarrhea (9.1%), and fatigue (9.1%). The most common grade 1 or 2 adverse events were fatigue (67.3%), nausea (38.2%), reduced appetite (36.4%), hypertension (34.5%), weight loss (23.6%), and diarrhea (21.8%). Discontinuations caused by adverse events were reported for 7.3% of patients.1

The investigators concluded that lenvatinib with or without everolimus had promising antitumor activity in late-line RCC, including in patients who had disease progression while receiving immune checkpoint inhibitors and cabozantinib.1


  1. Wiele AJ, Bathala TK, Hahn AW, et al. 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. Oncologist. 2021;26:476-482.

Related Items

Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: