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Ramucirumab Clinical Development: an Emerging Role in Gastrointestinal Tumors

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Abstract

Ramucirumab (IMC-1121B, LY3009806) is a fully human G1 monoclonal antibody that specifically targets vascular endotelial growth factor receptor 2 (VEGFR-2) with a substantially greater binding affinity than that of its natural ligands. Early clinical trials in patients with advanced solid tumors demonstrated that biologically relevant blood target concentrations are achievable with tolerable doses, and also showed some preliminary evidence of clinical activity. Several pivotal phase III trials have now been concluded and have led regulatory agencies to grant marketing authorization to ramucirumab for use as second line therapy in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma (as single agent or in combination with paclitaxel), in patients with advanced colorectal carcinoma (CRC) (in combination with infusional fluorouracil and irinotecan (FOLFIRI regimen)) and in patients with advanced non-small cell lung cancer (NSCLC) (in combination with docetaxel). In contrast, ramucirumab failed to significantly improve survival versus placebo as second line therapy in patients with advanced hepatocellular carcinoma (HCC). The aim of this review is to summarize the clinical development and emerging role of ramucirumab in gastrointestinal (GI) tumors, including relevant aspects of its mechanism of action, pharmacology, safety profile, and antitumor activity in gastric, HCC, and CRC carcinomas.

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Authors and Affiliations

  1. Center affiliated to the Red Tematica de Investigacion Cooperativa en Cancer (RTICC), Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, Hospital Universitario Virgen del Rocio, Sevilla, Spain

    Amparo Sanchez-Gastaldo & Reyes Gonzalez-Exposito

  2. Center affiliated to the Red Tematica de Investigacion Cooperativa en Cancer (RTICC), Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, Hospital Universitario Doce de Octubre, Madrid, Spain

    Rocío Garcia-Carbonero

  3. Oncology Department, Hospital Universitario Doce de Octubre, Avenida de Cordoba km 5.4, 28041, Madrid, Spain

    Rocío Garcia-Carbonero

Authors
  1. Amparo Sanchez-Gastaldo
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  2. Reyes Gonzalez-Exposito
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  3. Rocío Garcia-Carbonero
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Corresponding author

Correspondence to Rocío Garcia-Carbonero.

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Funding

RGC is partially funded by Fondo de Investigacion Sanitaria - Instituto de Salud Carlos III (PI10/02164, PI13/02295), Servicio Andaluz de Salud (PI-0259/2007) and RTICC-Instituto de Salud Carlos III (Spain) (R12/0036/0028).

Conflict of Interest

RGC has provided scientific advice to Lilly S.A. ASG and RGE declared no conflicts of interest.

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Sanchez-Gastaldo, A., Gonzalez-Exposito, R. & Garcia-Carbonero, R. Ramucirumab Clinical Development: an Emerging Role in Gastrointestinal Tumors. Targ Oncol 11, 479–487 (2016). https://doi.org/10.1007/s11523-016-0419-8

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  • DOI: https://doi.org/10.1007/s11523-016-0419-8

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