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

Preclinical data suggest that combined epidermal growth factor 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 CLIA-approved lab. There were 10 men; median number of prior therapies, 5. Overall, 2 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, 3 of 20 patients (15%) achieved stable disease (SD) ≥6 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/m2 IV weekly. In summary, erlotinib and cetuximab treatment was associated with SD ≥6 months/PR in 5 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.

http://mct.aacrjournals.org/content/early/2013/08/20/1535-7163.MCT-12-1208.abstract

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