Cabozantinib in patients with advanced and progressing hepatocellular carcinoma

Ghassan K. Abou-Alfa, Tim Meyer, Ann Lii Cheng, Anthony B. El-Khoueiry, Lorenza Rimassa, Baek Yeol Ryoo, Irfan Cicin, Philippe Merle, Yen Hsun Chen, Joong Won Park, Jean Frederic Blanc, Luigi Bolondi, Heinz Josef Klümpen, Stephen L. Chan, Vittorina Zagonel, Tiziana Pressiani, Min Hee Ryu, Alan P. Venook, Colin Hessel, Anne E. Borgman-HageyGisela Schwab, Robin K. Kelley

Research output: Contribution to journalArticle

Abstract

BACKGROUND Cabozantinib inhibits tyrosine kinases, including vascular endothelial growth factor receptors 1, 2, and 3, MET, and AXL, which are implicated in the progression of hepatocellular carcinoma and the development of resistance to sorafenib, the standard initial treatment for advanced disease. This randomized, double-blind, phase 3 trial evaluated cabozantinib as compared with placebo in previously treated patients with advanced hepatocellular carcinoma. METHODS A total of 707 patients were randomly assigned in a 2:1 ratio to receive cabozantinib (60 mg once daily) or matching placebo. Eligible patients had received previous treatment with sorafenib, had disease progression after at least one systemic treatment for hepatocellular carcinoma, and may have received up to two previous systemic regimens for advanced hepatocellular carcinoma. The primary end point was overall survival. Secondary end points were progression-free survival and the objective response rate. RESULTS At the second planned interim analysis, the trial showed significantly longer overall survival with cabozantinib than with placebo. Median overall survival was 10.2 months with cabozantinib and 8.0 months with placebo (hazard ratio for death, 0.76; 95% confidence interval [CI], 0.63 to 0.92; P=0.005). Median progression-free survival was 5.2 months with cabozantinib and 1.9 months with placebo (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.52; P
Original languageEnglish
Pages (from-to)54-63
Number of pages10
JournalNew England Journal of Medicine
Volume379
Issue number1
DOIs
Publication statusPublished - Jul 5 2018

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    Abou-Alfa, G. K., Meyer, T., Cheng, A. L., El-Khoueiry, A. B., Rimassa, L., Ryoo, B. Y., Cicin, I., Merle, P., Chen, Y. H., Park, J. W., Blanc, J. F., Bolondi, L., Klümpen, H. J., Chan, S. L., Zagonel, V., Pressiani, T., Ryu, M. H., Venook, A. P., Hessel, C., ... Kelley, R. K. (2018). Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. New England Journal of Medicine, 379(1), 54-63. https://doi.org/10.1056/NEJMoa1717002