Cohn, Allen LeeYoshino, TakayukiHeinemann, VolkerObermannova, RadkaBodoky, GyörgyPrausová, JanaGarcia-Carbonero, RocioCiuleanu, TudorGarcia-Alfonso, PilarPortnoy, David CVan Cutsem, EricYamazaki, KentaroClingan, Philip RPolikoff, JonathonLonardi, SaraO'Brien, Lisa MGao, LingYang, LingFerry, DavidNasroulah, FedericoTabernero, Josep2023-01-252023-01-252017-07-25http://hdl.handle.net/10668/11442To 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Colorectal cancerExposure–responseFOLFIRIRamucirumabSecond lineAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsColorectal NeoplasmsDisease-Free SurvivalFemaleHumansMaleresearch article28744667open access10.1007/s00280-017-3380-z1432-0843PMC5573752https://link.springer.com/content/pdf/10.1007/s00280-017-3380-z.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5573752/pdf