Open AccessExposure–Response Analysis of Necitumumab Efficacy in Squamous Non‐Small Cell Lung Cancer Patients
Author(s) -
Chigutsa E,
Long AJ,
Wallin JE
Publication year - 2017
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1002/psp4.12209
Subject(s) - gemcitabine , oncology , lung cancer , medicine , cisplatin , gompertz function , proportional hazards model , hazard ratio , cancer , chemotherapy , mathematics , confidence interval , statistics
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.