Lenvatinib was first approved in the U.S. on Feb. 13, 2015 for patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer. Approval for the additional indication for lenvatinib was based on Study 205, a phase II study suggesting the once-daily combination of lenvatinib, 18 mg, and everolimus, 5 mg, improved progression-free survival, objective response rate, and clinically meaningful overall survival compared to everolimus alone. Findings from that study were published in The Lancet Oncology (2015; 16:1473-82).
"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 [renal cell carcinoma] treatment for the past decade," principal investigator Robert Motzer, MD, of Memorial Sloan Kettering Cancer Center, New York said in a press release.
In Study 205, lenvatinib plus everolimus nearly tripled progression-free survival, compared to everolimus alone, with a 14.6-month median progression-free survival in patients treated with the combination. The objective response rate was 37% in the combination arm, compared to 6% in the single-treatment group.
Median overall survival increased 10.1 months in the combination group compared to the monotherapy arm.
Among the serious risks associated with the combination treatment: 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 embryo fetal toxicity.
Greater than 30% of those treated with lenvatinib and everolimus experienced diarrhea, fatigue, arthralgia/myalgia, decreased appetite, vomiting, nausea, stomatitis/oral inflammation, hypertension, peripheral edema, cough, abdominal pain, dyspnea, rash, weight decreased, hemorrhagic events, and proteinuria. At least 5% of subjects treated with the combination had renal failure.
Dr. Choueiri has received honoraria from the National Comprehensive Cancer Network and UpToDate and is a consultant/adviser for Bayer, Bristol-Myers Squibb, Eisai, Foundation Medicine, GlaxoSmithKline, Merck, Novartis, Pfizer, Prometheus, and Roche/Genentech. Dr. Motzer is a consultant/adviser for Eisai, GlaxoSmithKline, Novartis, and Pfizer.
More from Urology Times:
To get weekly news from the leading news source for urologists, subscribe to the Urology Times eNews.