title: 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.
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.
authors: Corresponding Author: Jennifer Wheler, The University of Texas MD Anderson Cancer Center, Department of Investigational Cancer Therapeutics, Unit 455, 1400 Holcombe Boulevard, Houston, TX 77030. jjwheler@mdanderson.org.
authors: Jennifer J
authors: JJ
authors: Wheler
authors: Apostolia M
authors: AM
authors: Tsimberidou
authors: Gerald S
authors: GS
authors: Falchook
authors: Ralph G
authors: RG
authors: Zinner
authors: David S
authors: DS
authors: Hong
authors: Jansina Y
authors: JY
authors: Fok
authors: Siqing
authors: S
authors: Fu
authors: Sarina A
authors: SA
authors: Piha-Paul
authors: Aung
authors: A
authors: Naing
authors: Razelle
authors: R
authors: Kurzrock
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000068818:Cetuximab; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011799:Quinazolines / Q000008:administration & dosage*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000068818:Cetuximab
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