Lenvatinib versus placebo in radioiodine-refractory thyroid cancer

Martin Schlumberger, Makoto Tahara, Lori J. Wirth, Bruce Robinson, Marcia S. Brose, Rossella Elisei, Mouhammed Amir Habra, Kate Newbold, Manisha H. Shah, Ana O. Hoff, Andrew G. Gianoukakis, Naomi Kiyota, Matthew H. Taylor, Sung Bae Kim, Monika K. Krzyzanowska, Corina E. Dutcus, Begoña De Las Heras, Junming Zhu, Steven I. Sherman

Research output: Contribution to journalArticle

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Abstract

Results The median progression-free survival was 18.3 months in the lenvatinib group and 3.6 months in the placebo group (hazard ratio for progression or death, 0.21; 99% confidence interval, 0.14 to 0.31; P<0.001). A progression-free survival benefit associated with lenvatinib was observed in all prespecified subgroups. The response rate was 64.8% in the lenvatinib group (4 complete responses and 165 partial responses) and 1.5% in the placebo group (P<0.001). The median overall survival was not reached in either group. Treatment-related adverse effects of any grade, which occurred in more than 40% of patients in the lenvatinib group, were hypertension (in 67.8% of the patients), diarrhea (in 59.4%), fatigue or asthenia (in 59.0%), decreased appetite (in 50.2%), decreased weight (in 46.4%), and nausea (in 41.0%). Discontinuations of the study drug because of adverse effects occurred in 37 patients who received lenvatinib (14.2%) and 3 patients who received placebo (2.3%). In the lenvatinib group, 6 of 20 deaths that occurred during the treatment period were considered to be drug-related.

Conclusions Lenvatinib, as compared with placebo, was associated with significant improvements in progression-free survival and the response rate among patients with iodine-131-refractory thyroid cancer. Patients who received lenvatinib had more adverse effects. (Funded by Eisai; SELECT ClinicalTrials.gov number, NCT01321554.)

Background Lenvatinib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, fibroblast growth factor receptors 1 through 4, platelet-derived growth factor receptor á, RET, and KIT, showed clinical activity in a phase 2 study involving patients with differentiated thyroid cancer that was refractory to radioiodine (iodine-131).

Methods In our phase 3, randomized, double-blind, multicenter study involving patients with progressive thyroid cancer that was refractory to iodine-131, we randomly assigned 261 patients to receive lenvatinib (at a daily dose of 24 mg per day in 28-day cycles) and 131 patients to receive placebo. At the time of disease progression, patients in the placebo group could receive open-label lenvatinib. The primary end point was progression-free survival. Secondary end points included the response rate, overall survival, and safety.

Original languageEnglish (US)
Pages (from-to)621-630
Number of pages10
JournalNew England Journal of Medicine
Volume372
Issue number7
DOIs
StatePublished - Feb 12 2015
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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    Schlumberger, M., Tahara, M., Wirth, L. J., Robinson, B., Brose, M. S., Elisei, R., Habra, M. A., Newbold, K., Shah, M. H., Hoff, A. O., Gianoukakis, A. G., Kiyota, N., Taylor, M. H., Kim, S. B., Krzyzanowska, M. K., Dutcus, C. E., De Las Heras, B., Zhu, J., & Sherman, S. I. (2015). Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. New England Journal of Medicine, 372(7), 621-630. https://doi.org/10.1056/NEJMoa1406470