TY - JOUR
T1 - Triple-drug chemotherapy regimens in combination with an anti-EGFR agent in metastatic colorectal cancer - prospects from phase II clinical trials
AU - Matos, Ignacio
AU - Noguerido, Alba
AU - Ros, Javier
AU - Mulet, Nuria
AU - Argilés, Guillem
AU - Elez, Élena
AU - Tabernero, Josep
PY - 2019/5/4
Y1 - 2019/5/4
N2 - © 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.
AB - © 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.
KW - antibody therapies
KW - biomarkers
KW - epidermal grow factor receptor
KW - Metastatic colorectal cancer
KW - triple-drug chemotherapy
U2 - 10.1080/13543784.2019.1599860
DO - 10.1080/13543784.2019.1599860
M3 - Article
C2 - 30905200
VL - 28
SP - 463
EP - 471
JO - Expert Opinion on Investigational Drugs
JF - Expert Opinion on Investigational Drugs
SN - 1354-3784
ER -