Faculty Collaboration Database

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. Oncotarget 2013 May;4(5):772-84

Date

06/27/2013

Pubmed ID

23800712

Pubmed Central ID

PMC3742837

DOI

10.18632/oncotarget.1028

Scopus ID

2-s2.0-84880303931 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

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.

Author List

Wheler J, Falchook G, Tsimberidou AM, Hong D, Naing A, Piha-Paul S, Chen SS, Heymach J, Fu S, Stephen B, Fok JY, Janku F, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Angiogenesis Inhibitors
Antibodies, Monoclonal, Humanized
Antineoplastic Agents
Antineoplastic Combined Chemotherapy Protocols
Bevacizumab
Boronic Acids
Bortezomib
Carcinoma, Non-Small-Cell Lung
Cetuximab
Dasatinib
ErbB Receptors
Erlotinib Hydrochloride
Female
Humans
Lung Neoplasms
Male
Middle Aged
Protein Kinase Inhibitors
Pyrazines
Pyrimidines
Quinazolines
Retrospective Studies
Sirolimus
Survival
Thiazoles
Treatment Outcome