Lenvatinib Improves Progression-Free Survival in Patients with Thyroid Cancer

Chicago—Patients with radioiodine-resistant, advanced differentiated thyroid cancer who received lenvatinib had a significantly greater progression-free survival compared with patients who received placebo, according to a multicenter, randomized, double-blind, placebo-controlled trial.

The median progression-free survival was 18.3 months in the lenvatinib group and 3.6 months in the placebo group (hazard ratio [HR], 0.21; P<.0001). After 26 months of treatment, 41% of patients in the lenvatinib group and 86% of patients in the placebo group had disease progression. The median overall survival was not reached in either group but favored the lenvatinib group, although the differences were not statistically significant (HR, 0.73; P=.1032).

All subgroups benefited from lenvatinib treatment, according to Martin Schlumberger, MD, the study’s lead author, who presented the results during an oral abstract session at the ASCO meeting. Eisai Co., Ltd., the manufacturer of lenvatinib, funded the trial.

Lenvatinib is an orally active, selective inhibitor of receptor tyrosine kinases. In December 2012, the drug received orphan drug designation from the FDA for follicular, medullary, anaplastic, and metastatic or locally advanced papillary thyroid cancer.

Of 60,000 thyroid cancer diagnoses each year, 85% are of the differentiated subtype. The standard treatment of surgery and radioiodine therapy typically cures the disease, although 5% to 15% of patients are resistant to radioiodine therapy. Dr. Schlumberger said patients with radioiodine-resistant, advanced differentiated thyroid cancer have a 10-year survival rate of 10%. Treatment options are limited for this group.

The SELECT [Study of Lenvatinib in Differentiated Cancer of the Thyroid] trial included 392 patients who had disease progression within the past 13 months. They were randomized to receive 24 mg of lenvatinib daily (n=261) or 24 mg of placebo daily (n=131) and remained on therapy until disease progression.

At baseline, the groups were well-balanced. The median age of participants was 64 years in the lenvatinib group and 61 years in the placebo group, while 52% and 43% of patients, respectively, were female. Approximately 25% of patients had previously received vascular endothelial growth factor (VEGF)-targeted therapy.

For the 299 patients who had never received VEGF-targeted therapy, the median progression-free survival was 18.7 months in the lenvatinib group and 3.6 months in the placebo group (HR, 0.20; P<.0001). For the 93 patients who had previously received VEGF-targeted therapy, the median progression-free survival was 15.1 months in the lenvatinib group and 3.6 months in the placebo group (HR, 0.22; P<.0001).

The objective response rate was 65% in the lenvatinib group and 2% in the placebo group (P<.0001). Of the patients who received lenvatinib, 2% had a complete response and 63% had a partial response. Of the patients who received placebo, none had a complete response and 2% had a partial response. Progressive disease was found in 7% of patients in the lenvatinib group and 40% in the placebo group.
The median duration of treatment was 13.8 months in the lenvatinib group and 3.9 months in the placebo group, while the median dose was 16.8 mg per day and 24 mg per day, respectively. The median time to first dose reduction was 3 months in the lenvatinib group and was not reached in the placebo group.

Serious treatment-emergent adverse events were found in 51% of patients in the lenvatinib group and 24% of patients in the placebo group. Fatal treatment-emergent adverse events were found in 8% and 5% of patients, respectively. Of the 20 deaths that occurred in the lenvatinib group, 6 were considered treatment related: general health deterioration (n=4), pulmonary embolism (n=1), and hemorrhagic stroke (n=1).—Tim Casey