EGFR status and daily dose: Effect on tumor growth inhibition in cancer patients treated with dacomitinib (PF-00299804).

e18093 Background: Dacomitinib (D) is a highly selective, irreversible small molecule pan-human epidermal growth factor (EGFR/HER) inhibitor. The effect of mean D daily dose (exposure) on tumor growth dynamics was analyzed using a longitudinal exposure-response tumor growth inhibition model. Methods: Estimated parameters included tumor shrinkage rate (KD), which changes over time as resistance to therapy develops according to an exponential decay function where λ = slope of the dynamic shrinkage rate change; and tumor growth rate constant (KL). eDose, the effect of mean D daily dose changes on tumor shrinkage rate, was tested in the base model to establish the best relationship between tumor shrinkage and drug exposure. Model parameters were estimated using a population (pop) approach. Pop pharmacodynamic analyses included data from 4 clinical trials (3 phase I and 1 phase II) of D (15–45 mg QD) in patients (pts) with advanced solid tumors. Multiple tumor size (SLD) measurements were collected from each p...