Exposure-Response Analyses of Ramucirumab from Two Randomized, Phase III Trials of Second-line Treatment for Advanced Gastric or Gastroesophageal Junction Cancer
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F17%3A00077991" target="_blank" >RIV/00209805:_____/17:00077991 - isvavai.cz</a>
Result on the web
<a href="http://mct.aacrjournals.org/content/16/10/2215.full-text.pdf" target="_blank" >http://mct.aacrjournals.org/content/16/10/2215.full-text.pdf</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1158/1535-7163.MCT-16-0895" target="_blank" >10.1158/1535-7163.MCT-16-0895</a>
Alternative languages
Result language
angličtina
Original language name
Exposure-Response Analyses of Ramucirumab from Two Randomized, Phase III Trials of Second-line Treatment for Advanced Gastric or Gastroesophageal Junction Cancer
Original language description
Ramucirumab is an IgG1 monoclonal antibody specific for the vascular endothelial growth factor receptor-2. Ramucirumab, 8 mg/kg every 2 weeks, administered as monotherapy (REGARD) or in combination with paclitaxel (RAINBOW), was safe and effective in patients with previously treated advanced gastric or gastroesophageal junction (GEJ) cancer. We evaluated exposure-efficacy and exposure-safety relationships of ramucirumab from two randomized, placebo-controlled phase III trials. Sparse pharmacokinetic samples were collected, and a population pharmacokinetic analysis was conducted to predict ramucirumab minimumtrough concentration at steady state (C-min,C-ss). Kaplan-Meier methods and Cox proportional hazards models were used to evaluate the ramucirumab exposure (C-min,C-ss)-efficacy relationship to overall survival (OS) and progression-free survival (PFS). Logistic regression analyses were used to evaluate exposure-safety relationships. Analyses included 321 ramucirumab + paclitaxel and 335 placebo + paclitaxel patients from RAINBOW and 72 ramucirumab and 35 placebo patients from REGARD. Exposure-efficacy analysis showed ramucirumab C-min,C-ss was a significant predictor of OS and PFS in both trials. Higher ramucirumab exposure was associated with longer OS and PFS. In RAINBOW, grade >= 3 hypertension, leukopenia, and neutropenia, but not febrile neutropenia, significantly correlated with Cmin, ss, with increased exposure leading to increased incidence. Exploratory exposure-response analyses suggest a positive relationship between efficacy and ramucirumab exposure with manageable toxicities at exposures generated from a dose of 8 mg/kg ramucirumab given every 2 weeks for patients with advanced gastric/GEJ cancer. These findings suggest an opportunity to further optimize benefit versus risk profiles of ramucirumab treatment in patients with gastric/GEJ cancer. (C) 2017 AACR.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Molecular Cancer Therapeutics
ISSN
1535-7163
e-ISSN
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Volume of the periodical
16
Issue of the periodical within the volume
10
Country of publishing house
US - UNITED STATES
Number of pages
8
Pages from-to
2215-2222
UT code for WoS article
000412220900015
EID of the result in the Scopus database
2-s2.0-85030683960