Lenvatinib Receives Approval for Advanced RCC

May 16, 2016

The FDA approved lenvatinib (Lenvima) in combination with everolimus for the treatment of advanced renal cell carcinoma.

The US Food and Drug Administration (FDA) approved lenvatinib (Lenvima) in combination with everolimus for the treatment of advanced renal cell carcinoma (RCC). The approval is for patients who were previously treated with an anti-angiogenic therapy.

"Lenvatinib plus everolimus is the first and only FDA-approved regimen that successfully combines treatments that employ tyrosine kinase and mTOR inhibition, the primary targets of advanced RCC treatment for the past decade," said Robert Motzer, MD, of Memorial Sloan Kettering Cancer in New York, in a press release. Motzer led a phase II study of the lenvatinib/everolimus combination in advanced RCC, the results of which led to the FDA approval. Lenvatinib received both breakthrough therapy designation and a priority review from the FDA.

That study included a lenvatinib/everolimus group (51 patients), a lenvatinib monotherapy group (52 patients), and an everolimus monotherapy group (50 patients). The median progression-free survival with the combination was 14.6 months compared with only 5.5 months with everolimus alone, for a hazard ratio of 0.37 (95% CI, 0.22–0.62). According to a paper published in the Lancet Oncology in 2015, the lenvatinib-alone group also had significantly better PFS than everolimus, but the FDA approval is for the combination only.

The objective response rate was 37% in the combination therapy patients, compared with 6% in the everolimus-alone patients; most of the combination therapy responses were partial responses, at 35%, and 2% were complete responses.

Though it did not reach significance, the lenvatinib/everolimus patients also had a longer median overall survival, at 25.5 months compared with 15.4 months with everolimus alone (hazard ratio, 0.67 [95% CI, 0.42–1.08]).

The most common adverse events (AEs) in the combination therapy patients included diarrhea, fatigue, arthralgia/myalgia, decreased appetite, and others. The most common serious AEs in that group included renal failure in 11% of patients, dehydration in 10%, anemia in 6%, and several others. Most patients (89%) receiving lenvatinib and everolimus required a dose reduction or interruption; the most common AEs leading to such interruptions or reductions were diarrhea (21%), fatigue (8%), and thrombocytopenia (6%). In the everolimus monotherapy group, 54% of patients required a dose reduction or interruption.

“Rates of [RCC] have been on the rise over the past several decades, and unfortunately, advanced RCC remains an incurable disease,” said Sumanta Kumar Pal, MD, of City of Hope in Duarte, California, in the press release. “Since the VEGF pathway is known to be involved in the growth of renal cell tumors, it is important to have a diverse offering of therapeutic options, including treatments that continue to target VEGF inhibition.”