Abstract | BACKGROUND: 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. 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.).
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Authors | 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 |
Journal | The New England journal of medicine
(N Engl J Med)
Vol. 372
Issue 7
Pg. 621-30
(Feb 12 2015)
ISSN: 1533-4406 [Electronic] United States |
PMID | 25671254
(Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Iodine Radioisotopes
- Phenylurea Compounds
- Protein Kinase Inhibitors
- Quinolines
- lenvatinib
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Topics |
- Adult
- Aged
- Disease-Free Survival
- Female
- Humans
- Iodine Radioisotopes
(therapeutic use)
- Kaplan-Meier Estimate
- Male
- Middle Aged
- Phenylurea Compounds
(adverse effects, therapeutic use)
- Protein Kinase Inhibitors
(adverse effects, therapeutic use)
- Quinolines
(adverse effects, therapeutic use)
- Thyroid Neoplasms
(drug therapy, radiotherapy)
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