Eisai Confirms 24 mg as Optimal Starting Dose of Lenvima (Lenvatinib) for Radioactive Iodine-Refractory Differentiated Thyroid Cancer in Post-Marketing Study

November 24, 2020 /BioValleyBIOON/ -- Eisai recently in European medicalTumorThe results of the Phase II clinical Study 211 (NCT02702388) evaluating Lenvima® (lenvatinib) for the treatment of radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC) were presented at the European Society for Medical Oncology (ESMO) Asia 2020 Virtual Congress.

Lenvima is an oral multi-receptor tyrosine kinase inhibitor. This study compared the efficacy and safety of two starting doses of Lenvima (18 mg vs. 24 mg, once daily). The results showed that in patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-R DTC), evaluated by the objective response rate (ORR) at Week 24 of treatment, compared with the United StatesFDACompared with the approved starting dose (24 mg), the lower starting dose (18 mg) did not meet the non-inferiority threshold. The data from this study support the selection of 24 mg as the appropriate starting dose for patients with radioiodine-refractory differentiated thyroid cancer (RAI-refractory DTC).

Following the granting of priority review status and approval of Lenvima for the treatment of patients with locally recurrent or metastatic, progressive radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), Study 211 served as a study for the U.S. Food and Drug Administration (FDA), a post-marketing commitment undertaken by the European Medicines Agency (EMA) and other regional regulatory authorities.

The primary objective of this randomized, double-blind, multicenter Phase II study was to determine whether a starting dose of Lenvima 18 mg once daily provides comparable efficacy (assessed by the overall response rate at Week 24 [ORRWK24]) and improved safety (assessed by treatment-emergent adverse events [TEAEs] of Grade ≥3) compared with a starting dose of 24 mg once daily.

In the primary efficacy analysis, the ORRWK24 was 57.3% (95% CI: 46.1–68.5) in the 24 mg dose group and 40.3% (95% CI: 29.3–51.2) in the 18 mg dose group. Based on the ORRWK24 results, the 18 mg dose group did not demonstrate non-inferiority to the 24 mg dose group (HR=0.50 [95% CI: 0.26–0.96]). The overall ORR was 64.0% (95% CI: 53.1–74.9) in the 24 mg dose group and 46.8% (95% CI: 35.6–57.9) in the 18 mg dose group.

In the primary safety analysis, the incidence of ≥ Grade 3 treatment-emergent adverse events (TEAEs) during the 24-week treatment period was similar between the 24 mg dose group and the 18 mg dose group, with no new or unexpected safety signals observed.

Thyroid Cancer (Image source: lifebridgehealth.org)

EisaiTumorDr. Takashi Owa, Chief Drug Development and Chief Discovery Officer of the Business Group, stated, “These study data reaffirm that the approved dose of Lenvima (24 mg once daily) provides clinically significant benefits and consistent safety in patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC). Through such studies, we are able to enhance healthcare providers’ understanding of our medicine, thereby helping them better serve patients with this difficult-to-treat cancer.”

Thyroid cancer is the most common endocrine malignancyTumor, global data indicate that its incidence is on the rise. It is estimated that by 2020, there will be 52,890 new cases of thyroid cancer in the United States, with women being three times more likely to develop thyroid cancer than men. The most common types of thyroid cancer, papillary and follicular carcinomas (including Hürthle cell carcinoma), are classified as differentiated thyroid cancer (DTC) and account for approximately 90% of all cases. Although most patients with DTC can be cured through surgery and radioactive iodine (RAI) therapy, those with persistent or recurrent disease have a poorer prognosis.

Lenvima is a kinase inhibitor discovered and developed by Eisai. This drug is an oral multi-receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). In addition to inhibiting normal cellular functions, Lenvima also inhibits other kinases associated with pathological angiogenesis, tumor growth, and cancer progression, including fibroblast growth factor (FGF) receptors FGFR1-4, platelet-derived growth factor receptor α (PDGFRα), KIT, and RET. Lenvima can reduceTumorRelevant macrophages increase activated cytotoxic T cells.

To date, the approved indications for Lenvima include: thyroid cancer, hepatocellular carcinoma (HCC), combination with everolimus for the treatment of renal cell carcinoma (second-line therapy), and combination with Keytruda (pembrolizumab, PD-1Tumorimmunotherapy) for the treatment of advanced endometrial cancer. In Europe, lenvatinib is marketed under the brand name Kisplyx for the treatment of renal cell carcinoma.

Eisai and Merck & Co., Inc. (known as MSD outside the United States and Canada) entered into a strategic collaboration in March 2018 to jointly develop and commercialize Lenvima globally. In March and August 2018, Lenvima received approval in Japan, the United States, and the European Union, respectively, becoming the first new first-line treatment approved in these markets in the past decade for advanced or unresectable hepatocellular carcinoma (HCC). In August of this year, the two companies submitted a new indication application for Lenvima in Japan for the treatment of unresectable thymic carcinoma. In June 2020, Lenvima was granted orphan drug designation in Japan for the treatment of unresectable thymic carcinoma.

In China, Lenvima (Lenvatinib) was approved in September 2018 as a monotherapy for the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC) who have not previously received systemic therapy. China is the world'sLiver CancerThe country with the largest patient population. In November 2018, Lenvima was launched in China, marking the first new systemic therapy for the first-line treatment of unresectable hepatocellular carcinoma (HCC) in China in nearly a decade.

In December 2019, the new indication of Lenvima for the treatment of differentiated thyroid cancer (DTC) was approved, marking the second indication for this drug to be approved in China. (Bioon.com)

Original Source: Eisai Announces New Investigational Data from Study 211 Evaluating the Starting Dose of LENVIMA® (lenvatinib) in Differentiated Thyroid Cancer at ESMO Asia 2020