EU regulator backs lenvatinib and everolimus for kidney cancer

25 Jul 2016

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for lenvatinib in combination with everolimus for the treatment of adult patients with advanced renal cell carcinoma (RCC) following one prior vascular endothelial growth factor (VEGF)-targeted therapy

Clear cell renal cell carcinoma accounts for approximately 80-90% of all kidney malignancies, and (RCC) represents 2-3% of all cancer cases, with the highest incidence in Western countries. During the last two decades, until recently, there has been a 2% increase in incidence of RCC worldwide.

“Progression-free survival results were statistically significant”

Lenvatinib was granted an accelerated assessment by the European Medicines Agency in October 2015, and the combination with everolimus to treat RCC was approved in America by the FDA this May. Lenvatinib selectively inhibits the kinase activities of several different receptors including vascular endothelial growth factor receptors (VEGFR), fibroblast growth factor receptors (FGFR), RET, KIT and platelet-derived growth factor receptors (PDGFR).

The opinion was issued following the evaluation of results from a pivotal Phase 2 trial, which show lenvatinib plus everolimus significantly extends progression-free survival in patients with unresectable advanced renal cell carcinoma versus everolimus alone. “This is a positive step forward for people with advanced renal cell carcinoma. The phase 2 trial was the first in which these two types of cancer drugs have been successfully combined in renal cell carcinoma, and the progression-free survival results were statistically significant,” comments Dr. Hilary Glen, Beatson West of Scotland Cancer Centre, Glasgow, UK.

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Increased median progression-free survival

The Phase 2 study, on which the CHMP opinion is based, shows that people with advanced renal cell carcinoma who progressed on previous VEGF therapy treated with the combination of lenvatinib plus everolimus experienced a median progression-free survival of 14.6 months compared with 5.5 months for those who received everolimus alone.

In subgroup analyses of the Phase 2 study, progression-free survival benefit is maintained across all subgroups regardless of high-risk poor prognosis renal cancer subgroups (MSKCC risk, baseline tumor size, metastasis site). For the secondary endpoints, updated median overall survival in the intent-to-treat study population was 25.5 months in the lenvatinib plus everolimus group compared with 15.4 months in the everolimus group.

Higher adverse events with the combination therapy

Adverse events were generally higher for the lenvatinib plus everolimus combination compared with everolimus alone. The most common grade 3 treatment-emergent adverse events in the lenvatinib plus everolimus group included constipation (37%), diarrhea (20%), fatigue or asthenia (14%) and hypertension (14%). The most commons grade 3 TEAEs in the everolimus group included anemia (12%), dyspnea (8%), hypertriglyceridemia (8%) and hyperglycemia (8%).

Results indicate that lenvatinib in combination with everolimus causes significant antitumor effects through the potent antiangiogenic activity of lenvatinib and direct antitumor activity of everolimus.

Lenvatinib, discovered and developed by Eisai, is an oral molecular targeted therapy that possesses a potent selectivity and a new Type V binding mode of kinase inhibition different to that of other tyrosine kinase inhibitors (TKI).

Lenvatinib has been approved for the treatment of refractory thyroid cancer in the United States, Europe, Russia, Switzerland, Australia, Canada, Singapore, Japan and South Korea and has been submitted for regulatory approval in Brazil. Lenvatinib was granted Orphan Drug Designation in Japan for thyroid cancer, in the United States for the treatment of follicular, medullary, anaplastic, and locally advanced papillary thyroid cancer and in Europe for follicular and papillary thyroid cancer.

Source: eCancer News
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