Lenvatinib versus Placebo in Radioiodine-Refractory Thyroid Cancer

• Published in: The New England journal of medicine Vol. 372; no. 7; pp. 621 - 630
• Main Authors: Schlumberger, Martin, Tahara, Makoto, Wirth, Lori J, Robinson, Bruce, Brose, Marcia S, Elisei, Rossella, Habra, Mouhammed Amir, Newbold, Kate, Shah, Manisha H, Hoff, Ana O, Gianoukakis, Andrew G, Kiyota, Naomi, Taylor, Matthew H, Kim, Sung-Bae, Krzyzanowska, Monika K, Dutcus, Corina E, de las Heras, Begoña, Zhu, Junming, Sherman, Steven I
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 12.02.2015
• Subjects: Adult; Aged; Appetite loss; Asthenia; Biomarkers; Clinical trials; Diarrhea; Disease-Free Survival; Double-blind studies; Drug dosages; Drug therapy; Fatigue; FDA approval; Female; Fibroblast growth factor receptors; Growth factor receptors; Humans; Hypertension; Iodine; Iodine Radioisotopes - therapeutic use; Kaplan-Meier Estimate; Laboratories; Male; Metastasis; Middle Aged; Nausea; Oncology; Patients; Phenylurea Compounds - adverse effects; Phenylurea Compounds - therapeutic use; Platelet-derived growth factor; Product development; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Quinolines - adverse effects; Quinolines - therapeutic use; Response rates; Side effects; Survival; Survival analysis; Thyroid cancer; Thyroid Neoplasms - drug therapy; Thyroid Neoplasms - radiotherapy; Vascular endothelial growth factor; Vascular endothelial growth factor receptors; Writers
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa1406470

In a phase 3, placebo-controlled study, lenvatinib was associated with a significant increase in progression-free survival (18.3 months vs. 3.6 months). Toxic effects with lenvatinib were substantial and included hypertension, diarrhea, and unexplained death. The 10-year survival rate among patients with differentiated thyroid cancer that is refractory to radioiodine (iodine-131) therapy is 10% from the time of detection of metastasis. 1 – 3 Although treatment options have historically been limited, efforts have first targeted vascular endothelial growth factor (VEGF) and its receptor (VEGFR), since this signaling network has been associated with the aggressiveness and metastasis of thyroid cancer. 4 – 6 However, other molecular pathways of tumor growth and maintenance beyond VEGF-driven angiogenesis contribute to the pathogenesis of thyroid cancer, including BRAF, NRAS, HRAS, RET/PTC, fibroblast growth factor receptor (FGFR), and platelet-derived growth factor receptor (PDGFR). 7 – 16 Because . . .