Erlotinib antitumor activity in non-small cell lung cancer models is independent of HER1 and HER2 overexpression.

BACKGROUND The human epidermal growth factor receptors HER1/EGFR and HER2 offer potential targets for treating non-small cell lung cancer (NSCLC). The antitumor efficacy of erlotinib (Tarceva, F. Hoffmann-La Roche, Ltd., Basel, Switzerland), a HER1/EGFR tyrosine-kinase inhibitor, was investigated in relation to HER1/EGFR and HER2 expression in five NSCLC xenograft models. MATERIALS AND METHODS Tumor-bearing mice were randomized to daily oral erlotinib, 50 mg/kg, or vehicle (controls) for 20-50 days. The antitumor efficacy of erlotinib was measured through tumor volume, serum tumor markers and tumor biomarkers. Tumor HER1/EGFR and HER2 expression were analyzed immunohistochemically. RESULTS Erlotinib reduced tumor volume in three NSCLC models. It also reduced serum tumor marker levels and the extent of inhibition correlated with tumor growth inhibition. HER1/EGFR and HER2 expression differed between the five tumor models, suggesting that expression level does not predict response to treatment. CONCLUSION Erlotinib showed differing antitumor activity in five NSCLC models, suggesting that its antitumor effect is independent of HER1/EGFR and HER2 overexpression.