%0 Journal Article
%A Cohn, Allen Lee
%A Yoshino, Takayuki
%A Heinemann, Volker
%A Obermannova, Radka
%A Bodoky, György
%A Prausová, Jana
%A Garcia-Carbonero, Rocio
%A Ciuleanu, Tudor
%A Garcia-Alfonso, Pilar
%A Portnoy, David C
%A Van Cutsem, Eric
%A Yamazaki, Kentaro
%A Clingan, Philip R
%A Polikoff, Jonathon
%A Lonardi, Sara
%A O'Brien, Lisa M
%A Gao, Ling
%A Yang, Ling
%A Ferry, David
%A Nasroulah, Federico
%A Tabernero, Josep
%T Exposure-response relationship of ramucirumab in patients with advanced second-line colorectal cancer: exploratory analysis of the RAISE trial.
%D 2017
%U http://hdl.handle.net/10668/11442
%X To characterize ramucirumab exposure-response relationships for efficacy and safety in patients with metastatic colorectal cancer (mCRC) using data from the RAISE study. Sparse pharmacokinetic samples were collected; a population pharmacokinetic analysis was conducted. Univariate and multivariate Cox proportional hazards models analyzed the relationship between predicted ramucirumab minimum trough concentration at steady state (C min,ss) and survival. Kaplan-Meier analysis was used to evaluate survival from patients in the ramucirumab plus folinic acid, 5-fluorouracil, and irinotecan (FOLFIRI) treatment arm stratified by C min,ss quartiles (Q). An ordered categorical model analyzed the relationship between C min,ss and safety outcomes. Pharmacokinetic samples from 906 patients were included in exposure-efficacy analyses; samples from 905 patients were included in exposure-safety analyses. A significant association was identified between C min,ss and overall survival (OS) and progression-free survival (PFS) (p  Exploratory exposure-response analyses suggested a positive relationship between efficacy and ramucirumab exposure with manageable toxicities in patients from the RAISE study with mCRC over the ranges of exposures achieved by a dose of 8 mg/kg every 2 weeks in combination with FOLFIRI.
%K Colorectal cancer
%K Exposure–response
%K FOLFIRI
%K Ramucirumab
%K Second line
%~