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 III study comparing necitumumab in combination with gemcitabine and cisplatin vs. gemcitabine and cisplatin alone in 1,014 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. The 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 body weight resulted in higher clearance and lower exposure, simulations showed that an 800 mg flat dose provided optimal response regardless of body weight.

Pharmacometrics: opportunity for reducing disease burden in the developing world: the case of Africa.

Pharmacometricians are virtually nonexistent in Africa and the developing world. The unrelenting burden of infectious diseases, which are often treated using medicines with narrow effectiveness and safety dose ranges, and the growing prevalence and recognition of non-communicable diseases represent significant threats for the patients, although affording an opportunity for advancing science. This article outlines the case for pharmacometricians to redirect their expertise to focus on the disease burden affecting the developing world.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e69; doi:10.1038/psp.2013.45; published online 28 August 2013.