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

2021 Year in Review - Renal-Cell Carcinoma - 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

Reference

  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
Reduced Starting Dose of Tyrosine Kinase Inhibitors in Patients with Metastatic Renal-Cell Carcinoma
JHOP - June 2022 Vol 12, No 3 published on June 16, 2022 in Original Article, Renal-Cell Carcinoma, Dose Escalation/Reduction
Minimal Activity with Sapanisertib in Refractory Renal-Cell Carcinoma
2021 Year in Review - Renal-Cell Carcinoma published on January 20, 2022 in Renal-Cell Carcinoma
Active Therapy Improves Survival versus BSC After Disease Progression on Nivolumab and Cabozantinib
2021 Year in Review - Renal-Cell Carcinoma published on January 20, 2022 in Renal-Cell Carcinoma
Real-World Treatment Patterns Have Drastically Changed Over the Past 5 Years
2021 Year in Review - Renal-Cell Carcinoma published on January 20, 2022 in Renal-Cell Carcinoma
Functional Imaging Predicts Outcomes in Patients Treated with Antiangiogenic Therapy
2021 Year in Review - Renal-Cell Carcinoma published on January 20, 2022 in Renal-Cell Carcinoma
Development of a Prognostic Biomarker Score for Nivolumab in Relapsed/Refractory Disease
2021 Year in Review - Renal-Cell Carcinoma published on January 20, 2022 in Renal-Cell Carcinoma
Nivolumab Rechallenge Associated with Moderate Efficacy
2021 Year in Review - Renal-Cell Carcinoma published on January 20, 2022 in Renal-Cell Carcinoma
Stereotactic Radiotherapy Delays Treatment Switch in Those with Oligoprogression
2021 Year in Review - Renal-Cell Carcinoma published on January 20, 2022 in Renal-Cell Carcinoma
Study 218: Higher Lenvatinib Starting Dose Trended Toward Better Outcomes
2021 Year in Review - Renal-Cell Carcinoma published on January 20, 2022 in Renal-Cell Carcinoma
BREAKPOINT: Cabozantinib Efficacious After Treatment with First-Line Immunotherapy
2021 Year in Review - Renal-Cell Carcinoma published on January 20, 2022 in Renal-Cell Carcinoma
© Amplity Health. All rights reserved.

Subscribe Today!

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

I'd like to receive: