Cometriq

Analyst Outlook

Cometriq (cabozantinib; Exelixis) is likely to be approved as a second-line therapy for patients with

advanced renal cell cancer (RCC), however, uptake will be dampened by the presence of programmed

death-1 (PD-1) inhibitor Opdivo (nivolumab; Bristol-Myers Squibb/Ono Pharmaceutical), which looks

set to become the standard of care in this setting. Inability to show a significant increase in overall

survival (OS) in patients treated with Cometriq versus the current standard of care means that

Cometriq is likely to be chosen behind Opdivo in the RCC treatment paradigm, and used in the third-
line setting as a salvage chemotherapy.

Drug Overview

Cometriq is an orally available small molecule inhibitor currently being developed by Exelixis as

second-line therapy for patients with relapsed or metastatic RCC. Cometriq has been shown to

suppress tumour growth and metastasis by inhibiting the activity of multiple tyrosine kinases

including MET, AXL, and vascular endothelial growth factor receptors (VEGFR). Vascular endothelial

growth factor (VEGF) production is upregulated in RCC and results in increased tumor vascularization

and disease progression. Standard first-line therapies such as Sutent (sunitinib; Pfizer) work by

targeting VEGF/VEGFR signalling; however, tumors often develop resistance to these anti-angiogenic

treatments. Aberrant expression of MET and AXL tyrosine kinases is associated with drug resistance

and poor disease prognosis; by targeting MET and AXL as well as VEGF/VEGFR signalling, Cometriq

may provide an alternative treatment option for patients in the relapsed setting (Choueiri et al., 2015).