Resistance to Afatinib and Cetuximab Combination Therapy in EGFR-mutant Lung Adenocarcinoma
Valentina Pirazzoli1, Ken Takezawa2, Elisa de Stanchina3, William Pao2 and Katerina Politi1
1Department of Pathology and Yale Cancer Center, Yale School of Medicine, New Haven, CT 06520, USA; 2Department of Medicine, Division of Hematology and Oncology, Vanderbilt University, Nashville, TN 37232, USA; 3Antitumor Assessment Core Facility, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA
BACKGROUND
The Epidermal Growth Factor Receptor (EGFR) T790M mutation confers acquired resistance to tyrosine kinase inhibitors (TKIs) in approximately 50% of drug-resistant EGFR mutant lung adenocarcinomas. Experiments using genetically engineered mouse models of EGFR mutant lung cancer have revealed that T790M-mediated resistance can be overcome using a second generation TKI, afatinib, in combin-ation with the anti-EGFR antibody, cetuximab. This drug combination is currently in clinical trials in patients with TKI-resistant tumors and is showing a promising ~ 40% response rate. Nevertheless, cases of afatinib+cetuximab resistance are beginning to emerge.
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