Implementing anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer: challenges and future perspectives

E. Martinelli, D. Ciardiello, G. Martini, T. Troiani, C. Cardone, P. P. Vitiello, N. Normanno, A. M. Rachiglio, E. Maiello, T. Latiano, F. De Vita, F. Ciardiello

Research output: Contribution to journalReview article

Abstract

Epidermal growth factor receptor (EGFR) inhibitors are valuable therapeutics in metastatic colorectal cancer (mCRC). Anti-EGFR monoclonal antibodies (MoAbs), such as cetuximab or panitumumab, in combination with chemotherapy are effective treatment options for patients with RAS and BRAF wild-type mCRC. Nevertheless, several issues are still open concerning the optimal use of anti-EGFR drugs in the continuum of care of mCRC. Novel approaches for increasing the efficacy of anti-EGFR therapies include better molecular selection of EGFR-dependent mCRC, intensification of chemotherapy, combination of anti-EGFR MoAbs and immune checkpoint inhibitors, and reintroduction of EGFR blockade or ‘rechallenge’ in selected patients who have previously responded to anti-EGFR MoAb therapy. An extensive translational research program was conducted in the Cetuximab After Progression in KRAS wIld-type colorectal cancer patients-Gruppo Oncologico dell' Italia Meridionale (CAPRI-GOIM) study with the aims of determining which subgroups of patients could benefit from the continuous inhibition of EGFR, from evaluating the role of liquid biopsy-based and its concordance with tissue-based molecular testing, and from investigating novel potential mechanisms of resistance to anti-EGFR therapies. In this review, we summarize the translational and clinical findings of the CAPRI-GOIM program in the context of the current knowledge of therapeutic strategies and of ongoing research on more appropriate uses of anti-EGFR therapies in RAS and BRAF wild-type mCRC patients.

Original languageEnglish
Pages (from-to)30-40
Number of pages11
JournalAnnals of Oncology
Volume31
Issue number1
DOIs
Publication statusPublished - Jan 2020

Keywords

  • anti-epidermal growth factor receptor monoclonal antibodies
  • liquid biopsy
  • metastatic colorectal cancer
  • molecular selection
  • predictive biomarkers
  • rechallenge therapy

ASJC Scopus subject areas

  • Hematology
  • Oncology

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  • Cite this

    Martinelli, E., Ciardiello, D., Martini, G., Troiani, T., Cardone, C., Vitiello, P. P., Normanno, N., Rachiglio, A. M., Maiello, E., Latiano, T., De Vita, F., & Ciardiello, F. (2020). Implementing anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer: challenges and future perspectives. Annals of Oncology, 31(1), 30-40. https://doi.org/10.1016/j.annonc.2019.10.007