Lenvatinib alone and in combination with everolimus resulted in improved progression-free survival in patients with metastatic renal cell carcinoma (mRCC) whose disease has progressed after 1 previous treatment with VEGF-targeted therapy, a new study published online ahead of print in the journal The Lancet Oncology has shown.1

Because mRCC is currently treated sequentially with single agents that target VEGF or mTOR, researchers sought to evaluate lenvatinib, everolimus, or the combination of both as second-line treatment for patients with mRCC.

For the multicenter, open-label, phase 2 study, researchers enrolled 153 patients with advanced or metastatic, clear-cell RCC that had progressed on or within 9 months of stopping VEGF-targeted therapy.

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Patients were randomly assigned 1:1:1 to receive lenvatinib 24 mg/day orally, everolimus 10 mg/day orally, or lenvatinib 18 mg/day plus everolimus 5 mg/day continuously in 28-day cycles until unacceptable toxicity or disease progression.

Results showed that the combination significantly improved median progression-free survival by 9.1 months compared with everolimus alone (HR=0.40; 95% CI: 0.24–0.68; P=.0005), but it did not significantly prolong progression-free survival compared with lenvatinib alone (HR = 0.66; 95% CI: 0.30–1.10; P=.12).

Researchers found that lenvatinib alone significantly improved progression-free survival compared with everolimus alone (HR = 0.61; 95% CI: 0.38–0.98; P=.048)

In regard to safety, grade 3 and 4 adverse events were less commonly associated with single-agent everolimus than single-agent lenvatinib or lenvatinib plus everolimus.

The most common grade 3 or 4 treatment-emergent adverse event was diarrhea, proteinuria, and anemia in the combination group, lenvatinib alone group, and single-agent everolimus group, respectively.

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Of note, one study drug-related death occurred in both the combination group and the single-agent lenvatinib group.

Lenvatinib is already approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with progressive, radioactive iodine-refractory differentiated thyroid cancer.


  1. Motzer RJ, Hutson TE, Glen H, et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial [published online ahead of print October 15, 2015]. Lancet Oncol. doi: 10.1016/S1470-2045(15)00290-9.