TY - JOUR
T1 - Revisiting clinical trials using EGFR inhibitor-based regimens in patients with advanced non-small cell lung cancer
T2 - A retrospective analysis of an MD Anderson Cancer Center phase I population
AU - Wheler, Jennifer
AU - Falchook, Gerald
AU - Tsimberidou, Apostolia M.
AU - Hong, David
AU - Naing, Aung
AU - Piha-Paul, Sarina
AU - Chen, Su S.
AU - Heymach, John
AU - Fu, Siqing
AU - Stephen, Bettzy
AU - Fok, Jansina Y.
AU - Janku, Filip
AU - Kurzrock, Razelle
PY - 2013/5
Y1 - 2013/5
N2 - 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 EGFRmutant 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.
AB - 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 EGFRmutant 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.
KW - EGFR mutation
KW - EGFR wild-type
KW - Non-small cell lung cancer
KW - Phase I trials
KW - Resistance
KW - Squamous cell
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UR - http://www.scopus.com/inward/citedby.url?scp=84880303931&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.1028
DO - 10.18632/oncotarget.1028
M3 - Article
C2 - 23800712
AN - SCOPUS:84880303931
SN - 1949-2553
VL - 4
SP - 772
EP - 784
JO - Oncotarget
JF - Oncotarget
IS - 5
ER -