RT Journal Article
T1 Exposure-response relationship of ramucirumab in patients with advanced second-line colorectal cancer: exploratory analysis of the RAISE trial.
A1 Cohn, Allen Lee
A1 Yoshino, Takayuki
A1 Heinemann, Volker
A1 Obermannova, Radka
A1 Bodoky, György
A1 Prausová, Jana
A1 Garcia-Carbonero, Rocio
A1 Ciuleanu, Tudor
A1 Garcia-Alfonso, Pilar
A1 Portnoy, David C
A1 Van Cutsem, Eric
A1 Yamazaki, Kentaro
A1 Clingan, Philip R
A1 Polikoff, Jonathon
A1 Lonardi, Sara
A1 O'Brien, Lisa M
A1 Gao, Ling
A1 Yang, Ling
A1 Ferry, David
A1 Nasroulah, Federico
A1 Tabernero, Josep
K1 Colorectal cancer
K1 Exposure–response
K1 FOLFIRI
K1 Ramucirumab
K1 Second line
AB 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.
YR 2017
FD 2017-07-25
LK http://hdl.handle.net/10668/11442
UL http://hdl.handle.net/10668/11442
LA en
DS RISalud
RD Apr 7, 2025