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Critical Appraisal of Ramucirumab (IMC-1121B) for Cancer Treatment: From Benchside to Clinical Use

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Abstract

Although antiangiogenic treatments have produced milestone advances in the treatment of several diseases, and have significantly extended the median survival of cancer patients, these agents share some weaknesses, including a limited impact on the overall cure rate, a fleeting effect because of redundant pathways or early appearance of resistance mechanisms, and the lack of predictive factors for treatment selection. Recent data suggest that antibodies targeting the vascular endothelial growth factor axis exert their activity through the inhibition of vascular endothelial growth factor receptor-2 phosphorylation, which has a pivotal role in the neoangiogenic process. Ramucirumab, a fully humanized monoclonal antibody specifically directed against the extracellular domain of the receptor, administered intravenously every 2 or 3 weeks, is emerging as a novel antiangiogenic opportunity. Starting with preclinical data and early clinical results, this concise review focuses on the development of the novel compound across multiple cancers (including gastrointestinal malignancies, breast cancer, lung carcinoma, and genitourinary tumors), and presents available data from randomized phase II and phase III trials. REGARD was the first phase III study to report on the efficacy of single-agent ramucirumab in patients with advanced cancer. Many other ongoing phase III trials are testing the efficacy of this interesting antiangiogenic compound as a single agent or in combination with chemotherapy in different cancer types.

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Conflict of interest

None of the authors have competing interests to disclose and no funding or editorial help was received in support of this manuscript. All authors approved the final version of the manuscript. Dr. Giuseppe Aprile was involved in the REGARD trial as clinical investigator. He has received consultancy and speaker’s honoraria from Roche, Eli-Lilly, Amgen, and Merck-Serono. Dr. Carmelo Pozzo has received consultancy honoraria from Eli-Lilly. Dr. Francesco Giuliani has been an invited speaker for Roche, Amgen, Merck-Serono, and Sanofi-Aventis. Dr. Marta Bonotto and Dr. Elena Ongaro have no financial interests to disclose.

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  1. Department of Medical Oncology, University and General Hospital, Piazzale S Maria della Misericordia, 33100, Udine, Italy

    Giuseppe Aprile, Marta Bonotto & Elena Ongaro

  2. Medical Oncology, Catholic University of the Sacred Heart, Rome, Italy

    Carmelo Pozzo

  3. Department of Medical Oncology, National Cancer Institute “G. Paolo II”, Bari, Italy

    Francesco Giuliani

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  1. Giuseppe Aprile
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Correspondence to Giuseppe Aprile.

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Aprile, G., Bonotto, M., Ongaro, E. et al. Critical Appraisal of Ramucirumab (IMC-1121B) for Cancer Treatment: From Benchside to Clinical Use. Drugs 73, 2003–2015 (2013). https://doi.org/10.1007/s40265-013-0154-8

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