FDA Approves Lenvatinib for Advanced Renal Cell Carcinoma

Nick Mulcahy

May 13, 2016

The US Food and Drug Administration (FDA) has approved lenvatinib (Lenvima, Eisai), in combination with everolimus, for the treatment of patients with advanced renal cell carcinoma who were previously treated with an anti-angiogenic therapy, the company announced today.

Lenvatinib, a multiple receptor tyrosine kinase inhibitor, was approved for refractory differentiated thyroid cancer last year.

The new approval, for use in advanced renal cell carcinoma, is based on results of a phase 2 registration study (Study 205) in which the combination of lenvatinib and everolimus demonstrated improved progression-free survival (PFS), objective response rate, and overall survival (OS) compared with everolimus alone.

"Lenvatinib plus everolimus is the first and only FDA-approved regimen that successfully combines treatments that employ tyrosine kinase and [mammalian target of rapamycin] inhibition, the primary targets of advanced [renal cell carcinoma] treatment for the past decade," said Robert Motzer, MD, from the Memorial Sloan Kettering Cancer Center, New York City, and the principal investigator of the study.

In Study 205, patients treated with a combination of lenvatinib and everolimus (n = 51) had a median PFS of 14.6 months (95% confidence interval [CI]: 5.9 - 20.1) compared with 5.5 months (95% CI: 3.5 - 7.1) for those treated with everolimus alone (n = 50); Hazard ratio [HR], 0.37; 95% CI: 0.22 - 0.62.

Thus, the combination resulted in a 63% reduction in the risk for disease progression or death compared with everolimus alone.

The objective response rate was 37% (95% CI: 24 - 52) with the combination compared with 6% (95% CI: 1 - 17) with everolimus alone.

Patients treated with the combination had a median OS of 25.5 months (95% CI: 16.4 - 32.1) compared with 15.4 months (95% CI: 11.8 - 20.6) for those treated with everolimus alone (HR, 0.67; 95% CI: 0.42 - 1.08).

In Study 205, the most common adverse reactions observed in patients treated with the combination (> 30%) were diarrhea, fatigue, arthralgia/myalgia, decreased appetite, vomiting, nausea, stomatitis/oral inflammation, hypertension, peripheral edema, cough, abdominal pain, dyspnea, rash, weight decrease, hemorrhagic events, and proteinuria.

The most common serious adverse reactions ( 5%) were renal failure (11%), dehydration (10%), anemia (6%), thrombocytopenia (5%), diarrhea (5%), vomiting (5%), and dyspnea (5%).

Adverse reactions led to dose reductions or interruption in 89% of patients receiving the combination and 54% in patients receiving everolimus alone.

The most common adverse reactions (≥ 5%) resulting in dose reductions in patients treated with the combination were diarrhea (21%), fatigue (8%), thrombocytopenia (6%), vomiting (6%), nausea (5%), and proteinuria (5%).

The company also states that serious adverse events related to treatment with the combination of lenvatinib and everolimus may include hypertension, cardiac dysfunction, arterial thromboembolic events, hepatotoxicity, proteinuria, diarrhea, renal failure and impairment, gastrointestinal perforation and fistula formation, QT interval prolongation, hypocalcemia, reversible posterior leukoencephalopathy syndrome, hemorrhagic events, impairment of thyroid-stimulating hormone suppression/thyroid dysfunction, and embryofetal toxicity.

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