Lenvatinib Meets Primary Endpoint in Phase III Differentiated Thyroid Cancer Study

Thyroid

The investigational agent lenvatinib (E7808) met its primary endpoint of progression-free survival (PFS) in the phase III SELECT trial, which compared lenvatinib to placebo in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC), according to Eisai Inc., the company that is developing the agent.

In the trial, lenvatinib demonstrated a statistically significant improvement in PFS, which Eisai plans to submit for marketing authorization in the United States, Japan, and Europe, the company said in a statement. In a phase II study of Lenvatinib, a selective inhibitor of VEGFR 1-3, FGFR 1-4, PDGFR-β, KIT and RET, treatment with the drug resulted in an overall response rate (ORR) of 59% and a PFS of 12.6 months for patients with advanced RR-DTC.

"These results show the potential role of the investigational drug lenvatinib in this rare, hard-to-treat cancer," Kenichi Nomoto, PhD, President, Oncology Product Creation Unit, Eisai Product Creation Systems, said in a press release. "RR-DTC remains an unmet need with a limited number of treatment options."

The randomized, placebo-controlled phase III SELECT study compared the PFS of patients with RR-DTC and radiographic evidence of disease progression within the prior 12 months. The 392 patients enrolled in the trial were treated with once-daily oral lenvatinib (24mg) versus placebo. Secondary endpoints of the study included ORR, overall survival, and safety. The five most common adverse reactions were hypertension, diarrhea, decreased appetite, decreased weight, and nausea, according to preliminary safety analyses. The study took place at over 100 sites in Europe, North and South America, and Asia.

In a phase II study investigating lenvatinib in 58 patients with advanced RR-DTC whose disease had progressed during the prior 12 months, the starting dose of lenvatinib was 24 mg once daily in repeated 28 day cycles until disease progression or development of unmanageable toxicities. Toxicities were managed with dose reduction in 35% of patients and 23% were ultimately withdrawn from the study due to toxicity.

Investigator assessed partial responses were observed in 29 patients (50%). A majority of responses (65%) were identified on the first imaging after initiation of therapy, at approximately 8 weeks. In 17 patients who had received prior treatment with VEGFR inhibitors, the response rate was 41%. For the 41 patients without prior VEGFR-targeted treatment, the response rate was 54%. At an 8-month follow-up presented at the 2012 ASCO Annual meeting, the median PFS was 12.6 months.

In the study, the most frequent reported treatment-related adverse events in this study were: hypertension 74% (Grade 3: 10%), proteinuria 60% (Grade 3: 10%), decreased weight 57% (Grade 3: 7%), diarrhea 55% (Grade 3: 10%) and fatigue 53% (Grade 3: 7%).

Lenvatinib was grated Orphan Drug Designation in the United States in December 2012 for follicular, medullary, anaplastic, and metastatic or locally advanced papillary thyroid cancer. It is currently under investigation as a potential treatment for thyroid, hepatocellular, endometrial and other solid tumor types.