Kim, Tae You; Yen, Chia-Jui; Al-Batran, Salah-Eddin; Ferry, David; Gao, Ling; Hsu, Yanzhi; Cheng, Rebecca; Orlando, Mauro; Ohtsu, Atsushi
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
2017Jun ; 8 ( 1 ) :.
PMID : 28634748
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Kim, Tae You -
Yen, Chia-Jui -
Al-Batran, Salah-Eddin -
Ferry, David -
Gao, Ling -
Hsu, Yanzhi -
Cheng, Rebecca -
Orlando, Mauro -
Ohtsu, Atsushi -
ABSTRACT
BACKGROUND: Ramucirumab is a recombinant human IgG1 neutralizing monoclonal antibody specific for vascular endothelial growth factor receptor-2. Second-line ramucirumab, in conjunction with paclitaxel (ramucirumab 8?mg/kg or placebo in combination with 80?mg/m(2) paclitaxel), has been shown to be effective and safe in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma in RAINBOW, a global phase III randomized clinical trial. We conducted an exploratory exposure-response analysis of efficacy and safety of ramucirumab in East Asian patients from the RAINBOW trial.
METHODS: Using sparse pharmacokinetic samples collected in the RAINBOW trial, a population pharmacokinetic analysis was conducted to predict ramucirumab minimum trough concentration at steady state (C (min,ss)) using a nonlinear mixed-effect modeling approach. Kaplan-Meier and Cox proportional hazards analyses were conducted to evaluate ramucirumab exposure (C (min,ss)) and efficacy relationship by overall survival and progression-free survival. Exposure-safety relationships were assessed descriptively.
RESULTS: Two hundred and twenty-two East Asian patients were included in this exposure-response analysis. Higher ramucirumab C (min,ss) was associated with longer overall survival (p?=?0.0115) and progression-free survival (p?=?0.0179) in this patient cohort. Patients with higher ramucirumab C (min,ss) (??6.87?ng/ml median) had higher incidences of grade ?? leukopenia and neutropenia, but not febrile neutropenia or hypertension.
CONCLUSIONS: This exploratory analysis suggests a positive relationship between efficacy and ramucirumab exposure with manageable toxicities in East Asian patients from RAINBOW, consistent with the overall exposure-response analysis from this trial. A regimen with a higher dosage of ramucirumab warrants further consideration for East Asian patients with gastric/GEJ cancer.
East Asian patients; Exposure response; Gastric cancer; Ramucirumab; Vascular endothelial growth factor receptor-2
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