Cabometyx (cabozantinib) for Treatment of Patients with Advanced Renal Cell Carcinoma, United States of America
Cabometyx (cabozantinib), developed by Exelixis, is used for treatment of patients with advanced renal cell carcinoma (RCC). The new drug application (NDA) for Cabometyx (cabozantinib) was submitted to the US Food and Drug Administration (FDA) on 23 December 2015.
The FDA approved the drug for treatment of renal cell carcinoma in patients who have already received prior anti-angiogenic therapy on 25 April 2016. The European Medical Agency (EMA) also granted marketing authorisation approval (MAA) for Cabometyx on 28 January 2016.
Exelixis and Ipsen jointly announced the licensing agreement for further development and marketing of cabozantinib indications outside the US, Canada and Japan on 29 February 2016.
Renal cell carcinoma
Renal cell carcinoma, also known as renal adenocarcinoma, is a condition that involves malignant or cancerous cells forming in the lining of kidney tubules.
RCC is the seventh most common cancer in men and tenth most common cancer in women. An estimated 62,700 new cases will be diagnosed and approximately 14,240 patients will die from renal cell carcinoma in 2016.
The disease is associated with symptoms such as blood in urine, lumps in the abdominal region, loss of appetite, weight loss, anaemia, chronic pain in the abdomen, flank pain and swelling of the varicocele (veins around a testicle), excessive hair growth in females, pale skin and vision problems.
In most cases, the tumours of renal cell carcinoma regulate the function of Von Hippel Lindau (VHL) protein, which results in stabilisation of the hypoxia inducible transcription factors and leads to up-regulation of VEGF, MET and AXL.
The exact cause of the disease is unknown, but family history of the illness, high blood pressure, horseshoe kidney, polycystic kidney disease, smoking and Von Hippel Lindau disease are some of the factors that are known to increase the risk of developing kidney cancer.
Cabometyx's mechanism of action
Cabometyx is a tablet formulation available in 20mg, 40mg and 60mg dosages. It is a tyrosine kinase inhibitor, which inhibits activity of the RET, MET, VEGFR2 (vascular endothelial growth factor 2) and other receptor tyrosine kinases.
These receptor tyrosine kinases are responsible for normal cellular function and pathogenesis such as oncogenesis, tumour angiogenesis.
By inhibiting the activity of these receptor kinases, it blocks oncogenesis, metastasis and supply of blood vessels and nutrients to the tumours.
Clinical trials on Cabometyx
The US FDA and EMA approvals for CABOMETYX (cabozantinib) were based on results obtained from the METEOR phase III pivotal trial.
METEOR was an open label, randomised and phase III trial, which enrolled 658 patients with advanced renal cell carcinoma to evaluate the drug's safety and efficacy.
The clinical trial was conducted in more than 200 sites in 26 counties and patients were mainly enrolled from Western Europe, North America and Australia.
Patients in the trial were randomised in 1:1 ration to receive either 60mg of cabozantinib or 10mg of everolimus daily and were divided into different groups based on the number of VEGF receptor TKI therapies received prior to the randomisation.
The study met its primary end-point of improvement in the progression-free survival. Cabozantinib demonstrated a 42% reduction in the disease progression rate or death when compared to everolimus.
The period of progression-free survival for patients administered with cabozantinib was 7.4 months, compared with 3.8 months for the everolimus arm.
The overall survival period in patients of the cabozantinib arm was 20 months, while it was 15 months for those in the everolimus arm.