Exposure-Response Analyses of Ramucirumab from Two Randomized, Phase III Trials of Second-line Treatment for Advanced Gastric or Gastroesophageal Junction Cancer
DC Field | Value | Language |
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dc.contributor.author | Tabernero, Josep | - |
dc.contributor.author | Ohtsu, Atsushi | - |
dc.contributor.author | Muro, Kei | - |
dc.contributor.author | Van Cutsem, Eric | - |
dc.contributor.author | Oh, Sang Cheul | - |
dc.contributor.author | Bodoky, Gyorgy | - |
dc.contributor.author | Shimada, Yasuhiro | - |
dc.contributor.author | Hironaka, Shuichi | - |
dc.contributor.author | Ajani, Jaffer A. | - |
dc.contributor.author | Tomasek, Jiri | - |
dc.contributor.author | Safran, Howard | - |
dc.contributor.author | Chandrawansa, Kumari | - |
dc.contributor.author | Hsu, Yanzhi | - |
dc.contributor.author | Heathman, Michael | - |
dc.contributor.author | Khan, Azhar | - |
dc.contributor.author | Ni, Lan | - |
dc.contributor.author | Melemed, Allen S. | - |
dc.contributor.author | Gao, Ling | - |
dc.contributor.author | Ferry, David | - |
dc.contributor.author | Fuchs, Charles S. | - |
dc.date.accessioned | 2021-09-03T01:00:14Z | - |
dc.date.available | 2021-09-03T01:00:14Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2017-10 | - |
dc.identifier.issn | 1535-7163 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/82152 | - |
dc.description.abstract | 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. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | AMER ASSOC CANCER RESEARCH | - |
dc.subject | DOUBLE-BLIND | - |
dc.subject | TRASTUZUMAB | - |
dc.subject | SAFETY | - |
dc.title | Exposure-Response Analyses of Ramucirumab from Two Randomized, Phase III Trials of Second-line Treatment for Advanced Gastric or Gastroesophageal Junction Cancer | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Oh, Sang Cheul | - |
dc.identifier.doi | 10.1158/1535-7163.MCT-16-0895 | - |
dc.identifier.scopusid | 2-s2.0-85030683960 | - |
dc.identifier.wosid | 000412220900015 | - |
dc.identifier.bibliographicCitation | MOLECULAR CANCER THERAPEUTICS, v.16, no.10, pp.2215 - 2222 | - |
dc.relation.isPartOf | MOLECULAR CANCER THERAPEUTICS | - |
dc.citation.title | MOLECULAR CANCER THERAPEUTICS | - |
dc.citation.volume | 16 | - |
dc.citation.number | 10 | - |
dc.citation.startPage | 2215 | - |
dc.citation.endPage | 2222 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.subject.keywordPlus | DOUBLE-BLIND | - |
dc.subject.keywordPlus | TRASTUZUMAB | - |
dc.subject.keywordPlus | SAFETY | - |
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