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The role of antiangiogenic agents in the treatment of patients with advanced colorectal cancer according to K-RAS status

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Abstract

Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer worldwide. Recently, it has been found that about 40 % of patients with CRC have mutations in the K-RAS gene. Several clinical trials have showed that patients with metastatic colorectal cancer (mCRC) who present tumour-promoting mutations in signalling pathways involving the epidermal growth factor receptor (EGFR), which includes activating K-RAS mutations, do not respond to anti-EGFR drugs such as panitumumab and cetuximab. Hence, K-RAS status is now considered an important negative predictive factor for response to anti-EGFR drugs. Moreover, K-RAS status seems to have also a prognostic role in CRC, but this fact is somewhat controversial. Activity of antiangiogenic agents seems not to be influenced by K-RAS gene status. Tumour angiogenesis has attracted interest in attempts to improve the management of mCRC. The vascular endothelial growth factor (VEGF) pathway is fundamental to the regulation of angiogenesis, and research has focused on developing agents that selectively target it. In this way, the anti-VEGF antibody bevacizumab in combination with chemotherapy has provided important clinical benefits in terms of response rate, progression-free survival and overall survival to patients with mCRC. Efficacy data of bevacizumab in K-RAS wild-type patients seem to be comparable with the efficacy data observed with anti-EGFR therapies in a cross-trial comparison. Although there is a lack of prospective and randomized data in this setting, the combination of chemotherapy plus antiangiogenic agents could be considered as an effective alternative for the treatment of mCRC with independence of K-RAS gene status. Here, we review the available data we have in the literature of the use of antiangiogenic strategies in the treatment of mCRC nowadays.

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Acknowledgments

The authors wish to thank Ana Martín from HealthCo SL (Madrid, Spain) for her help in preparing the first draft of this manuscript. The necessary scientific meetings were supported financially by Roche Farma, S.A. of Spain. We also thank Simone Boniface of in Science Communications, Springer Healthcare, who provided post-submission medical writing support. This support was funded by Roche. Roche Farma, S.A. of Spain, was given the opportunity to comment on the first draft of the manuscript, but all the decisions about its content were taken by the authors based on editorial merit. All authors have approved the final version of the submitted manuscript.

Conflict of interest

The authors declare that they do not have any conflict of interest that may inappropriately influence this work. Dr. EG received unrestricted grants for research from GSK, Novartis, Pfizer, and Bayer and honoraria for lectures and advisory boards from Amgen, Merck and Roche.

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Authors and Affiliations

  1. Medical Oncology Service, Hospital General Universitario Gregorio Marañón, C/Doctor Esquerdo, 46, 28007, Madrid, Spain

    Pilar García-Alfonso

  2. Medical Oncology Service, Hospital Universitario Ramón y Cajal, Madrid, Spain

    Enrique Grande

  3. Medical Oncology Service, Hospital Miguel Servet, Zaragoza, Spain

    Eduardo Polo

  4. Medical Oncology Service, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain

    Ruth Afonso

  5. Medical Oncology Service, Hospital Universitario Virgen Macarena, Sevilla, Spain

    Juan José Reina

  6. Medical Oncology Service, Complejo Hospitalario Universitario Xeral-Ciés, Vigo, Spain

    Mónica Jorge

  7. Medical Oncology Service, Hospital Arnau de Vilanova, Valencia, Spain

    Juan Manuel Campos

  8. Medical Oncology Service, Hospital Universitario La Paz, Madrid, Spain

    Virginia Martínez

  9. Medical Oncology Service, Hospital Clínico San Juan, Alicante, Spain

    Cristina Ángeles

  10. Medical Oncology Service, Hospital del Mar, Barcelona, Spain

    Clara Montagut

Authors
  1. Pilar García-Alfonso
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  2. Enrique Grande
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  3. Eduardo Polo
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  4. Ruth Afonso
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  5. Juan José Reina
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  6. Mónica Jorge
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  7. Juan Manuel Campos
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  8. Virginia Martínez
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  9. Cristina Ángeles
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  10. Clara Montagut
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Corresponding author

Correspondence to Pilar García-Alfonso.

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García-Alfonso, P., Grande, E., Polo, E. et al. The role of antiangiogenic agents in the treatment of patients with advanced colorectal cancer according to K-RAS status. Angiogenesis 17, 805–821 (2014). https://doi.org/10.1007/s10456-014-9433-6

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  • DOI: https://doi.org/10.1007/s10456-014-9433-6

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