Axitinib is a novel, oral, multitargeted tyrosine kinase inhibitor, which inhibits vascular endothelial growth factor receptors 1, 2, and 3 at subnanomolar concentrations in vitro. In the phase III clinical trial in patients with metastatic renal cell carcinoma, axitinib showed a high objective response rate, and significantly prolonged progression-free survival compared with sorafenib. Thus, it is the first drug that has proven the concept of sequencing tyrosine kinase inhibitors in second-line treatment in a phase III prospective randomized trial. Although generally well tolerated and associated with a low incidence of grade 3 or 4 toxicities, axitinib shows a distinct pattern of adverse events that require monitoring and management. The most common adverse events observed with axitinib include diarrhea, hypertension, fatigue, nausea, and vomiting. This article summarizes the most important adverse events observed and proposes recommendations for their monitoring, prevention, and treatment. The recommendations are based on the existing literature and discussion by an expert group of international physicians and nurses specialized in oncologic treatment of metastatic renal cell carcinoma, which gathered in July 2011 in London, UK. Proactive assessment and management of adverse events during axitinib therapy can minimize treatment interruptions and ensure optimal effect of treatment.
*Renal Cancer Unit, Department of Medicine, Royal Marsden, London, UK
†H. Lee Moffitt Cancer Center, Tampa, FL
‡Cleveland Clinic Cancer Institute, Cleveland, OH
§Massachusetts General Hospital, Boston, MA
∥N.N. Blokhin Russian Cancer Research Center, Moscow, Russia
¶M.D. Anderson Cancer Center, Houston
#Texas Oncology PA Sammons Cancer Center/Baylor, Dallas, TX
**Department of Urology, University of Munich, Munich, Germany
J.L. is currently receiving consulting fees from Pfizer, Novartis, and GSK; grants (to his institution) from Pfizer and Novartis; and compensation for speaker’s bureau services from Pfizer and Novartis. M.F. is currently receiving consulting fees from Bayer/Onyx, Eisai, Novartis, Pfizer, and Prometheus, and compensation for speaker’s bureau services from Pfizer, Bayer, Prometheus, Novartis, and GSK; has received honoraria from Pfizer; compensation for speaker’s bureau services from Genentech, educational presentations from Novartis and Wyeth; and travel support from Pfizer and compensation from Novartis and Prometheus; and his institution is currently receiving a research funding from Altor, Amgen, Aveo, Bayer/Onyx, Eisai, Novartis, Pfizer, and Prometheus. L.W. is on the speaker’s bureau and has received travel support and honoraria from Pfizer. S.N. has received honoraria and travel support from Pfizer. K.O. has received has received honoraria and travel support from Pfizer. L.P. has received research funding, compensation for speaker’s bureau services, educational presentations, and honoraria from Pfizer and compensation from Novartis and GSK. V.G. has received honoraria and travel support from Pfizer. E.J. receives consulting fees from Aveo, BMS, GSK, Novartis, and research funding Pfizer and has received honoraria and travel support from Pfizer. His institution receives research funding from Aveo, GSK, Novartis, and Pfizer. L.A. is currently receiving consulting fees and compensation for speaker’s bureau services from Bayer; has received honoraria and travel support from Pfizer, and is employed by US Oncology. M.S. is a board member, is currently receiving consultancy fees, research funding, compensation for speaker’s bureau services; receives travel support; and received compensation for expert testimony, educational presentations, honoraria, and travel support from Pfizer. Pfizer sponsored a meeting held to discuss data, after which a paper was written based on the meeting results. All authors were paid honoraria and M.F., L.W., S.N., K.O., V.G., E.J., L.A., and M.S. received travel support for the meeting itself (section 2 disclosures), but not for the paper development (section 1 disclosure).
Reprints: James Larkin, MD, PhD, Renal Cancer Unit, Department of Medicine, Royal Marsden Hospital, London SW3 6JJ, UK. E-mail: firstname.lastname@example.org.