Afatinib plus Cetuximab Delays Resistance Compared to Single-Agent Erlotinib or Afatinib in Mouse Models of TKI-Naïve EGFR L858R-Induced Lung Adenocarcinoma

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Valentina PirazzoliKaterina Politi

Abstract

The EGFR tyrosine kinase inhibitors (TKIs), erlotinib and afatinib, have transformed the treatment of advanced EGFR-mutant lung adenocarcinoma. However, almost all patients who respond develop acquired resistance on average approximately 1 year after starting therapy. Resistance is commonly due to a secondary mutation in EGFR (EGFR(T790M)). We previously found that the combination of the EGFR TKI afatinib and the EGFR antibody cetuximab could overcome EGFR(T790M)-mediated resistance in preclinical models. This combination has shown a 29% response rate in a clinical trial in patients with acquired resistance to first-generation TKIs. An outstanding question is whether this regimen is beneficial when used as first-line therapy. Using mouse models of EGFR-mutant lung cancer, we tested whether the combination of afatinib plus cetuximab delivered upfront to mice with TKI-naïve EGFR(L858R)-induced lung adenocarcinomas delayed tumor relapse and drug-resistance compared with single-agent TKIs. Afatinib plus cetuximab markedly delayed the time to relapse and incidence of drug-resistant tumors, which occurred in only 63.6% of the mice, in contrast to erlotinib or afatinib treatment where 100% of mice developed resistance. Mechanisms of t...Continue Reading

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Citations

Sep 27, 2016·Trends in Cancer·Erika Ilagan, Brendan D Manning
Feb 1, 2017·Current Oncology Reports·Bin-Chi LiaoJames Chih-Hsin Yang
Nov 9, 2017·Nature Reviews. Clinical Oncology·Ibiayi Dagogo-Jack, Alice T Shaw
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Apr 3, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alexis B CortotJacques Cadranel
Mar 21, 2020·Cancer Research·Jacqueline H StarrettKaterina Politi
May 26, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alexis B CortotJacques Cadranel
Sep 15, 2021·Cold Spring Harbor Perspectives in Medicine·Anna Arnal-EstapéKaterina Politi

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