학술논문
Exposure‐response relationship of ramucirumab in RANGE, a randomized phase III trial in advanced urothelial carcinoma refractory to platinum therapy
Document Type
article
Author
Wit, Ronald; Powles, Thomas; Castellano, Daniel; Necchi, Andrea; Lee, Jae‐Lyun; Heijden, Michiel S; Matsubara, Nobuaki; Bamias, Aristotelis; Fléchon, Aude; Sternberg, Cora N; Drakaki, Alexandra; Yu, Evan Y; Zimmermann, Annamaria H; Long, Amanda; Walgren, Richard A; Gao, Ling; Bell‐McGuinn, Katherine M; Petrylak, Daniel P
Source
British Journal of Clinical Pharmacology. 88(7)
Subject
Language
Abstract
AimsPatients with advanced urothelial carcinoma (UC) who progress after platinum-based chemotherapy have a poor prognosis, and there is a medical need to improve current treatment options. Ramucirumab plus docetaxel significantly improved progression-free survival but not overall survival (OS) in platinum-refractory advanced UC (RANGE trial; NCT02426125). Here, we report the exposure-response (ER) of ramucirumab plus docetaxel using data from the RANGE trial.MethodsPharmacokinetic (PK) samples were collected (cycle 1-3, 5, 9 [day 1] and 30 days from treatment discontinuation), and PK data were analysed using population PK (popPK) analysis. The minimum ramucirumab concentration after first dose administration (Cmin,1 , or trough concentration immediately prior to the second dose) was derived by popPK analysis and used as the exposure parameter for ER analysis. Cox proportional hazards regression models and matched case-control analyses were used to evaluate the relationship between Cmin,1 and OS. The Cmin,1 relationship with safety was assessed descriptively.ResultsSeveral poor prognostic factors (ECOG 1, haemoglobin concentration