Faculty Collaboration Database

Combining erlotinib and cetuximab is associated with activity in patients with non-small cell lung cancer (including squamous cell carcinomas) and wild-type EGFR or resistant mutations. Mol Cancer Ther 2013 Oct;12(10):2167-75

Date

08/22/2013

Pubmed ID

23963360

Pubmed Central ID

PMC4138057

DOI

10.1158/1535-7163.MCT-12-1208

Scopus ID

2-s2.0-84885621292 (requires institutional sign-in at Scopus site)   33 Citations

Abstract

Preclinical data suggest that combined EGF receptor (EGFR) targeting with an EGFR tyrosine kinase inhibitor and an anti-EGFR monoclonal antibody may be superior over single-agent targeting. Therefore, as part of a phase I study, we analyzed the outcome of 20 patients with non-small cell lung cancer treated with the combination of erlotinib and cetuximab. EGFR mutation status was ascertained in a Clinical Laboratory Improvement Amendment-approved laboratory. There were 10 men; median number of prior therapies was five. Overall, two of 20 patients (10%) achieved partial response (PR), one of whom had a TKI-resistant EGFR insertion in exon 20, time to treatment failure (TTF) = 24+ months, and the other patient had squamous cell histology (EGFR wild-type), TTF = 7.4 months. In addition, three of 20 patients (15%) achieved stable disease (SD) ≥6 six months (one of whom had wild-type EGFR and squamous cell histology, and two patients had an EGFR TKI-sensitive mutation, one of whom had failed prior erlotinib therapy). Combination therapy with ertotinib plus cetuximab was well tolerated. The most common toxicities were rash, diarrhea, and hypomagnesemia. The recommended phase II dose was erlotinib 150 mg oral daily and cetuximab 250 mg/m(2) i.v. weekly. In summary, erlotinib and cetuximab treatment was associated with SD ≥ six months/PR in five of 20 patients with non-small cell lung cancer (25%), including individuals with squamous histology, TKI-resistant EGFR mutations, and wild-type EGFR, and those who had progressed on prior erlotinib after an initial response. This combination warrants further study in select populations of non-small cell lung cancer.

Author List

Wheler JJ, Tsimberidou AM, Falchook GS, Zinner RG, Hong DS, Fok JY, Fu S, Piha-Paul SA, Naing A, 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
Antibodies, Monoclonal, Humanized
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Cetuximab
Drug Resistance, Neoplasm
ErbB Receptors
Erlotinib Hydrochloride
Female
Humans
Male
Maximum Tolerated Dose
Middle Aged
Mutation
Neoplasm Staging
Quinazolines