Opdivo (nivolumab – BMS) and Cometriq (cabozantinib -Exelixis) demonstrated positive results in studies of patients with kidney cancer. Renal cell carcinoma is the most common type of kidney cancer in adults, accounting for more than 100,000 deaths annually. Globally, the five-year survival rate for those diagnosed with metastatic, or advanced kidney cancer, is 12.1 percent.
In the case of Opdivo, CheckMate-025, an open-label, randomized Phase III study evaluating Opdivo (nivolumab) versus everolimus in previously-treated patients with advanced or metastatic renal cell carcinoma (RCC) was stopped early because an assessment conducted by the independent Data Monitoring Committee (DMC) concluded that the study met its endpoint, demonstrating superior overall survival in patients receiving Opdivo compared to the control arm.
Cometriq hit its primary endpoint of besting standard everolimus in extending the lives of patients with renal cell carcinoma already treated with a VEGF inhibitor. In top-line results, Exelixis’ treatment charted a statistically significant increase in progression-free survival compared to everolimus, sold by Novartis ($NVS) as Afinitor, and reduced the relative risk of tumor growth or death by 42%.
Cabozantinib met its primary endpoint based on results from 375 of the study’s 658 enrolled patients, as determined by the trial’s independent radiology committee, but the company will have to wait for final data on the secondary goal of overall survival. At the interim analysis, overall survival trends are favoring cabozantinib over everolimus, Exelixis said, but the company will have to wait for 2016 to make any conclusions on the data.
Opdivo is a PD-1 immune check point inhibitor, which blocks signals transmitted by cancer cells that abrogate the anti-tumor cytotoxic t-cell immune response.
Cabozantinib is an anticancer drug for inhibiting tumor growth, angiogenesis and metastasis. It is orally bioavailable and has a potential anti-neoplastic activity. The small anti-cancer compound targets multiple receptor tyrosine kinases (RTK) including the vascular endothelial growth factor receptor 2 (VEGFR-2) and hepatocyte growth factor receptor (MET). They are responsible for development and progression of many cancers.
Hepatocyte growth factor (HGF / scatter factor – SF) induces the epithelial-mesenchymal switch via loss of E-cadherin. This is the first step in motility and invasion. HGF binds to the MET receptor triggering a signal transduction cascade, which cabozantinib inhibits.
Cabozantinib won approval in 2012 to treat a rare form of thyroid cancer, the first step in what Exelixis hoped would be a string of regulatory successes that would expand its indications. But two years later, cabozantinib missed its primary endpoint in a big Phase III trial in prostate cancer, roughly halving Exelixis’ market cap and leading the biotech to lay off about 70% of its workforce and shift its bets to kidney cancer. The top-line success in renal cell carcinoma sent Exelixis’ shares up as much as 50%.
Cometriq and Opdivo represent just two of the most exciting pathways that have been elucidated in cancer development over the past 10 years.