Cabometyx (cabozantinib; Exelixis/Ipsen/Takeda) is an orally available small molecule inhibitor which has been shown to suppress tumor growth and metastasis by inhibiting the activity of multiple tyrosine kinases including MET, AXL, and vascular endothelial growth factor receptor (VEGFR). VEGF production is upregulated in renal cell carcinoma and results in increased tumor vascularization and disease progression.
Standard first-line therapies such as Sutent (sunitinib; Pfizer) work by targeting VEGF/VEGFR signaling; 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 signaling, Cabometyx may provide an alternative treatment option for patients in the relapsed setting.
Cabometyx (cabozantinib; Exelixis/Ipsen/Takeda) was originally approved as a monotherapy for the second-line treatment of renal cell carcinoma (RCC), though it has subsequently been approved for first-line use based on positive data from the Phase II CABOSUN trial (ClinicalTrials.gov identifier: NCT01835158). Cabometyx's uptake has been strong, and this is set to continue with the drugs inclusion in combination therapies currently in development.
The Phase III CheckMate 9ER trial (ClinicalTrials.gov identifier: NCT03141177) is investigating the safety and efficacy of both Cabometyx + Opdivo (nivolumab; Bristol-Myers Squibb/Ono Pharmaceutical) doublet therapy and Cabometyx + Opdivo + Yervoy (ipilimumab; Bristol-Myers Squibb/Ono Pharmaceutical) triplet therapy.
If approved, he Cabometyx + Opdivo + Yervoy combination would be the only triplet therapy available for the treatment of RCC, though the considerable cost of this regimen may prove too high for cost-conservative markets.
The impact on Cabometyx sales from its inclusion in a combination therapy will be dampened as it will reach the market after the competing Tecentriq (atezolizumab; Roche/Chugai) + Avastin (bevacizumab; Genentech/Roche/Chugai), Keytruda (pembrolizumab; Merck & Co) + Inlyta (axitinib; Pfizer),
and Bavencio (avelumab; Merck KGaA/Pfizer) + Inlyta combinations.
Key Topics Covered:
- Drug Overview
- Product Profiles
- Cabometyx : Renal cell carcinoma (RCC)
- Cabometyx : Hepatocellular carcinoma (HCC)
LIST OF FIGURES
- Cabometyx for RCC - SWOT analysis
- The authors drug assessment summary of Cabometyx for RCC
- Cabometyx sales for RCC across the US, Japan, and five major EU markets, by country, 2017-26
- Cabometyx for HCC - SWOT analysis
- The authors drug assessment summary of Cabometyx for HCC
LIST OF TABLES
- Cabometyx drug profile
- Cabometyx Phase III data in RCC
- Cabometyx's ongoing trials in RCC
- Cabometyx sales for RCC across the US, Japan, and five major EU markets, by country ($m), 2017-26
- Cabometyx drug profile
- Cabometyx Phase III trial in HCC
- Cabometyx Phase II data in HCC
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