The Efficacy of Lenvatinib Plus Everolimus in Patients with Metastatic Renal Cell Carcinoma Exhibiting Primary Resistance to Front-Line Targeted Therapy or Immunotherapy

Abstract

Background: Patients with primary refractory metastatic renal cell carcinoma (mRCC) have a dismal prognosis and poor response to subsequent treatments. While there are several approved second-line therapies, it remains critical to choose the most effective treatment regimen.

Patients and methods: We identified 7 patients with clear cell mRCC who had primary resistance to vascular endothelial growth factor (VEGF)-targeted tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitor (ICI) combination therapy. The patients were treated with lenvatinib (a multitargeted TKI) plus everolimus (a mammalian target of rapamycin inhibitor). Among these 7 patients, 2 had prior TKI therapy, 3 had prior ICI therapy, and 2 had prior TKI and ICI therapy. We collected the patients' clinical characteristics, molecular profiles, treatment durations, and toxicity outcomes.

Results: The median time to progression on prior therapies was 1.5 months. Lenvatinib plus everolimus was used either as a second-line (n = 4) or third-line (n = 3) therapy. As best responses, 3 patients had partial responses and 3 achieved stable disease. Patients were followed for ≥17 months; progression-free survival ranged from 3 to 15 months, and overall survival ranged from 4 to 17 months.

Conclusion: These 7 cases provide real-world data for the use of lenvatinib plus everolimus in patients with mRCC with primary resistance to first-line VEGF-targeted TKIs or ICI combination therapy.

Keywords: Immune checkpoint inhibitor; Kidney cancer; Primary refractory; Second-line therapy tyrosine kinase inhibitor; mTOR inhibitor.

Figure 1.

Patients with mRCC that was primarily refractory to first-line therapy were identified (n=7) and treated with the combination of lenvatinib and everolimus. Their time on the combination therapy (blue bars) and their efficacy outcomes are shown here. mRCC, metastatic renal cell carcinoma.

Figure 2.

Representative images from 2 patients with primary refractory mRCC (to prior TKI [Patient 1; images a and b] or ICI therapy [Patient 5; images c and d]) who had a partial response after lenvatinib plus everolimus treatment. Images shown are of the pretreatment scans (a, c), with tumors clearly visible, and the posttreatment scan (b, d), where tumor size is much reduced. ICI, immune checkpoint inhibitor; mRCC, metastatic renal cell carcinoma; TKI, tyrosine kinase inhibitors.