Exposure–Response Analysis of Necitumumab Efficacy in Squamous Non‐Small Cell Lung Cancer Patients

We sought to describe the exposure-response relationship of necitumumab efficacy in squamous non-small cell lung cancer patients and evaluate intrinsic and extrinsic patient descriptors that may guide dosing. SQUIRE was a phase 3 study comparing necitumumab in combination with gemcitabine and cisplatin versus gemcitabine and cisplatin alone in 1014 patients. An integrated model for tumor size dynamics and overall survival was developed, where reduction in tumor size results in a decrease in survival hazard. Change in tumor size was characterized using linear growth and first order shrinkage. Overall survival was described using a combination of a Weibull function and Gompertz function for the hazard, with dynamic tumor size being a predictor for the hazard. Although bodyweight resulted in higher clearance and lower exposure, simulations showed that an 800 mg flat dose provided optimal response regardless of bodyweight. This article is protected by copyright. All rights reserved.