Dreamin’ of Cabo.
Top Line: We recently saw lenvatinib successfully challenge sorafenib, the longtime reigning champion of systemic therapy for hepatocellular carcinoma (HCC). Now there’s a new VEGF inhibitor vying for the title.
The Study: This phase 3 trial randomized 707 patients with previously treated HCC to cabozantinib versus placebo in a 2:1 fashion. Sorry if this is not the Cabo you were hoping for, but it wasn’t a bad option for these patients. At least in theory. Cabozantinib is a multi-tyrosine kinase inhibitor of not only VEGF but also MET and AXL. All three of these TKs are induced by tumor hypoxia, with the last two prime culprits for resistance to traditional antiangiogenic agents (read: sorafenib). Among other crimes, MET and AXL promote epithelial-to-mesenchymal transition, invasion, and metastasis putting them squarely on the rad bio most-wanted list. So how did cabo do clinically? Median progression free survival was extended from a meager 2 to a modest 5 months, and even the ambitious primary endpoint of overall survival was significantly improved from a median of 8 to 10 months.
Bottom Line: Cabozantinib is a new inhibitor of multiple tyrosine kinases including VEGF, MET, and AXL with proven activity and even a survival advantage for patients with previously treated HCC. | Abou-Alfa, N Engl J Med 2018
The Study: This phase 3 trial randomized 707 patients with previously treated HCC to cabozantinib versus placebo in a 2:1 fashion. Sorry if this is not the Cabo you were hoping for, but it wasn’t a bad option for these patients. At least in theory. Cabozantinib is a multi-tyrosine kinase inhibitor of not only VEGF but also MET and AXL. All three of these TKs are induced by tumor hypoxia, with the last two prime culprits for resistance to traditional antiangiogenic agents (read: sorafenib). Among other crimes, MET and AXL promote epithelial-to-mesenchymal transition, invasion, and metastasis putting them squarely on the rad bio most-wanted list. So how did cabo do clinically? Median progression free survival was extended from a meager 2 to a modest 5 months, and even the ambitious primary endpoint of overall survival was significantly improved from a median of 8 to 10 months.
Bottom Line: Cabozantinib is a new inhibitor of multiple tyrosine kinases including VEGF, MET, and AXL with proven activity and even a survival advantage for patients with previously treated HCC. | Abou-Alfa, N Engl J Med 2018
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