Revisiting Clinical Trials Using EGFR Inhibitor-Based Regimens in Patients with Advanced Non-Small Cell Lung Cancer: A Retrospective Analysis of an MD Anderson Cancer Center Phase I Population
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Jennifer Wheler1, Gerald Falchook1, Apostolia M. Tsimberidou1, David Hong1, Aung Naing1, Sarina Piha-Paul1, Su S. Chen2, John Heymach3, Siqing Fu1, Bettzy Stephen1, Jansina Y. Fok1, Filip Janku1, Razelle Kurzrock4
1 Department of Investigational Cancer Therapeutics – a Phase I Clinical Trials Program, The University of Texas MD Anderson Cancer Center, Texas
2 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Texas
3 Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Texas
4 Moores Cancer Center, University of California, San Diego
Jennifer Wheler, email:
Keywords: EGFR mutation, EGFR wild-type, non-small cell lung cancer, phase I trials, resistance, squamous cell
Received: May 10, 2013 Accepted: June 2, 2013 Published: June 4, 2013
Purpose: Single-agent EGFR inhibitor therapy is effective mainly in patients with lung cancer and EGFR mutations. Treating patients who develop resistance, or who are insensitive from the outset, often because of resistant mutations, other aberrations or the lack of an EGFR mutation, probably requires rational combinations. We therefore investigated the outcome of EGFR inhibitor-based combination regimens in patients with heavily-pretreated non-small cell lung cancer (NSCLC) referred to a Phase I Clinic.
Methods: We reviewed the electronic records of patients with NSCLC treated with an EGFR inhibitor-based combination regimen: erlotinib and cetuximab; erlotinib, cetuximab and bevacizumab; erlotinib and dasatinib; erlotinib and bortezomib; or cetuximab and sirolimus.
Results: EGFR mutations were detected in 16% of patients (21/131). EGFR inhibitor-based combination regimens were administered to 15 patients with EGFR-mutant NSCLC and 24 with EGFR wild-type disease. Stable disease (SD) ≥6 months/partial remission (PR) was attained in 20% of EGFR-mutant patients (3/15; two with sensitive mutations and secondary resistance to prior erlotinib, and one with a resistant mutation), as well as 26% of evaluable patients (5/19) with wild-type disease. One of three evaluable patients with squamous cell histology achieved SD for 26.5 months (EGFR wild-type, TP53-mutant, regimen=erlotinib, cetuximab and bevacizumab).
Conclusions: Eight of 34 evaluable patients (24%) with advanced, refractory NSCLC evaluable for response achieved SD ≥6 months/PR (PR=3; SD ≥6 months=5) on EGFR inhibitor-based combination regimens (erlotinib, cetuximab; erlotinib, cetuximab and bevacizumab; and, erlotinib, bortezomib), including patients with secondary resistance to single-agent EGFR inhibitors, resistant mutations, wild-type disease, and, squamous histology.
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