The European Commission ( EC ) has issued a marketing authorisation for Kisplyx ( Lenvatinib ) in combination with Everolimus ( Afinitor ) for the treatment of adult patients with advanced renal cell carcinoma ( RCC ) following one prior vascular endothelial growth factor (VEGF)-targeted therapy.
Lenvatinib was granted an accelerated assessment by the European Medicines Agency in October 2015.
Marketing authorisation follows the evaluation of results from a pivotal phase II trial, which showed that Lenvatinib plus Everolimus significantly extended progression-free survival in patients with unresectable advanced renal cell carcinoma versus Everolimus alone.
The study evaluated 153 people living with advanced renal cell carcinoma who had progressed after one previous VEGF therapy.
Patients experienced a median progression-free survival of 14.6 months when treated with Lenvatinib in combination with Everolimus ( n=51 ), compared with 5.5 months for those who received Everolimus alone ( n=50 ) ( hazard ratio, HR=0.40; 95% CI: 0.24-0.67; p=0.0005 ).
Updated median overall survival in the study population was 25.5 months in the Lenvatinib plus Everolimus group compared with 15.4 months in the Everolimus group ( HR=0.59; 95% CI 0.36 – 0.97 ).
For Lenvatinib in combination with Everolimus, the most common any-grade treatment-emergent adverse events ( TEAEs ) reported in the Lenvatinib plus Everolimus group were diarrhoea, decreased appetite and fatigue.
The most common TEAEs of grade 3 or higher were diarrhoea, fatigue and hypertension.
Exploratory subgroup analyses of the phase II study presented at the American Society of Clinical Oncology ( ASCO ) Annual Meeting 2016, found that progression-free survival benefit was maintained across all subgroups regardless of high risk poor prognosis renal cancer subgroups ( MSKCC risk, baseline tumour size, metastasis site ).
Renal cell carcinoma represents 2-3% of all cancer diagnoses and originates in the lining of the tubules, the very small tubes in the kidney that are involved in the blood filtration process to remove waste products.
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 ).
Recent additional data in human RCC xenograft models indicate that Lenvatinib in combination with Everolimus causes significant antitumour effects through the potent antiangiogenic activity of lenvatinib and direct antitumour activity of Everolimus.
Everolimus is a selective mTOR ( mammalian target of rapamycin ) inhibitor. mTOR is a key serine-threonine kinase, the activity of which is known to be upregulated in a number of human cancers. ( Xagena )
Source: Eisai, 2016