Triple-drug chemotherapy regimens in combination with an anti-EGFR agent in metastatic colorectal cancer - prospects from phase II clinical trials

Ignacio Matos, Alba Noguerido, Javier Ros, Nuria Mulet, Guillem Argilés, Élena Elez, Josep Tabernero

Research output: Contribution to journalArticleResearch

5 Citations (Scopus)

Abstract

© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. Introduction: The addition of monoclonal antibody (mAb) epidermal growth factor receptor (EGFR) inhibitors to classic chemotherapy doublet backbones has improved survival of metastatic colorectal cancer (mCRC). However, the role of triple-drug chemotherapy regimens in combination with an anti-EGFR mAb inhibitor is not yet clear. Areas covered: The activity of triple-drug chemotherapy regimens when combined with an anti-EGFR mAb in mCRC patients is examined. We describe the overall safety and tolerability profiles based on a literature review of all published phase I and II clinical trials in this setting. Drug exposure, tumor mutational status, and metastases resectability are discussed. A review of PubMed and abstracts of major oncology congresses from 2009 to 2018, with MeSH and full-text search terms for clinical trials of anti-EGFR for ‘metastatic’ or ‘advanced’ ‘colorectal cancer/adenocarcinoma’ was implemented. Only English language publications were included. Expert opinion: Efficacy data from phase II trials are promising, but the safety profiles are not as encouraging; the development of severe diarrhea and acneiform rash limit the drug exposure that is critical for improved outcomes. Phase II studies of these triplet chemotherapy/anti-EGFR mAb combinations have focused on conversion therapy in liver-limited disease or in the first-line setting in advanced disease. The identification of biomarkers of response and toxicity may support the use of personalized medicine and more precise design of phase III trials.
Original languageEnglish
Pages (from-to)463-471
JournalExpert Opinion on Investigational Drugs
Volume28
DOIs
Publication statusPublished - 4 May 2019

Keywords

  • antibody therapies
  • biomarkers
  • epidermal grow factor receptor
  • Metastatic colorectal cancer
  • triple-drug chemotherapy

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