Lenvatinib Lands New Indication for Differentiated Thyroid Cancer in China

Lenvatinib (Lenvima) is now indicated for the treatment of differentiated thyroid cancer (DTC) in China as a result of application acceptance by the National Medical Products Administration of China, according to a press release from Eisai Co., Ltd.¹

The indication was based on data from the SELECT trial, a global phase III multicenter, randomized, double-blind, placebo-controlled study of lenvatinib in patients with locally recurrent or metastatic radioactive iodine (RAI)-refractory DTC.

In the trial, lenvatinib significantly prolonged progression-free survival (PFS). The median PFS observed in the lenvatinib group was 18.3 months compared with the 3.6 months observed in the placebo group (HR, 0.21, 99% CI, 0.14-0.31;P< 0.001). Lenvatinib also led to a higher objective response rate (ORR) of 64.8% versus 1.5% with placebo. Additionally, responses were rapid, occurring within a median of 2 months after initiation of treatment. The occurrence of complete responses (CRs) in the lenvatinib totaled 1.5% (n = 4). No CRs were seen in the placebo group.

Adverse events (AEs) occurred in both study groups. The most common reported all-grades AEs were hypertension, diarrhea, fatigue, asthenia, weight loss, decreased appetite, and nausea.

Patients in the SELECT trial were randomized 2:1 to either 24 mg of lenvatinib once daily or an equal dosage of placebo once daily. Patients who experienced disease progression in the placebo group were eligible to switch to treatment with lenvatinib. The trial enrolled 261 patients in the lenvatinib arm and 113 patients in the placebo group. The study evaluated these patients for the primary endpoint, PFS, in addition to the 2 key secondary endpoints, ORR and overall survival.²

All trial patients were required to have DTC; measurable disease according to RECIST 1.1; 131I-refractory/resistant disease; adequate renal, liver, bone marrow, and blood coagulation function; and show radiographic evidence of disease progression within 12 months before randomization. Participants were also required to have prior treatment with 1 or fewer vascular endothelial growth factor (VEGF) targeted therapies.²

In the press release, Eisai Co., Ltd stated, &ldquo;In China, approximately 190,000 new cases of thyroid cancer are diagnosed each year, and approximately 8,600 are likely to die annually. Although treatment is possible for most types of thyroid cancer, there are few treatment options available once thyroid cancer has progressed, therefore it remains a disease with significant unmet medical needs.&rdquo;

The SELECT trial is ongoing in China. The study has passed its originally targeted completion date of March 2019.²

Lenvatinib, a VEGF kinase inhibitor, is approved for the treatment of thyroid cancer in over 55 countries, including the United States (US). In the US, the drug is also indicated for the treatment of renal cell carcinoma and hepatocellular carcinoma, while these indications are also approved in more than 50 countries each as well. Recently,&nbsp;lenvatinib was approved in combination with pembrolizumab (Keytruda)for treatment of advanced endometrial cancer in the US, Australia, and Canada.¹

References

1. Eisai: Additional Indication for Lenvima (Lenvatinib) for Differentiated Thyroid Cancer Accepted in China [press release]. Tokyo, Japan: Eisai Co., Ltd; December 2, 2019. https://bit.ly/2Lr2Nka. Accessed December 5, 2019.
2. A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Lenvatinib (E7080) in 131I-Refractory Differentiated Thyroid Cancer (DTC) (SELECT). ClinicalTrials.gov. https://bit.ly/2OVqjYI. Accessed December 5, 2019.