Lenvatinib: New Hope for Radioiodine-resistant Differentiated Thyroid Cancer

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Lenvatinib: New Hope for Radioiodine-resistant Differentiated Thyroid Cancer
Lenvatinib: New Hope for Radioiodine-resistant Differentiated Thyroid Cancer

CHICAGO, IL—Lenvatinib, a new targeted tyrosine kinase inhibitor, delays disease progression by 14.7 months and shows promising clinical efficacy against differentiated thyroid cancer (DTC) that has developed radioiodine resistance, according to findings from the phase 3 double-blind, randomized, placebo-controlled SELECT study, presented at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.

Based on the SELECT trial findings, the coauthors are confident lenvatinib will “eventually become a standard treatment for radioiodine-resistant differentiated thyroid cancer,” according to lead study author Martin Schlumberger, MD, professor of oncology at the University Paris Sud in Paris, France.

Median progression-free survival (PFS) for patients in the lenvatinib group was 18.3 months compared with 3.6 months among patients receiving placebo (hazard ratio [HR], 0.21; 95% CI: 0.14-0.31; P < 0.0001). The median overall survival (OS) has not yet been reached.

“Response rates were extremely high,” Dr. Schlumberger said.

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Although complete response (CR) was reported for only four patients (2%) in the lenvatinib study arm, 165 (63%) patients in that group had partial responses (PRs; tumor shrinkage), compared with two patients (2%) on placebo. Median time to lenvatinib response was 2.0 months.

Lenvatinib targets VEGFR1-3, FGFR 1-4, PDGFR-β, KIT and RET.

In the SELECT phase 3 trial, 392 patients with advanced, radioiodine-resistant differentiated thyroid cancer were randomly assigned 2:1 to receive placebo (n=131) or lenvatinib (n=261). Patients assigned to receive placebo were allowed to cross over and receive lenvatinib upon disease progression.

The most common adverse events associated with lenvatinib were hypertension (68%), diarrhea (60%), fatigue/asthenia (59%), decreased appetite and weight (50% and 46%), and nausea/vomiting (46%). Grade 3 or higher treatment-related adverse events seen in 5% or more of patients included hypertension (42%), proteinuria (10%), weight loss (10%), fatigue/asthenia 9%), diarrhea (8%), and appetite decrease (5%).

“The dose was reduced in 68% of patients and discontinued due to adverse events in 14.2% of patients,” Dr. Schlumberger reported.

Of 20 lenvatinib-treated patient deaths, six were considered to be treatment-related by investigators. These included one death each attributed to pulmonary embolism, hemorrhagic stroke, and four deaths classified as “general health deterioration,” Dr. Schlumberger reported.

Differentiated thyroid cancer is the most common type of thyroid malignancy, representing 85% of the 65,000 new thyroid cancers diagnosed each year in the United States. Up to 15% of patients with differentiated thyroid cancer develop radioiodine resistance and these patients have a 10-year survival rate of 10% from the time of detected metastasis, Dr. Schlumberger noted

The U.S. Food and Drug Administration approved sorafenib, another targeted tyrosine kinase inhibitor for radioiodine-resistant DTC in November 2013.

“As little as a year ago, this group of patients had no effective treatment options,” he added. “It's remarkable that we now have two active drugs in this setting, both of them tyrosine kinase inhibitors.”

Lenvatinib is currently undergoing phase 2 and phase 3 clinical trials for patients with liver, lung, and kidney cancers.

Reference

  1. Schlumberger M, Tahara M, Wirth LJ et al. Abstract LBA6008. Presented at: 2014 American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2014; Chicago, IL.

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