Exposure-Response Analyses of Ramucirumab from Two Randomized, Phase III Trials of Second-line Treatment for Advanced Gastric or Gastroesophageal Junction Cancer

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Exposure-Response Analyses of Ramucirumab from Two Randomized, Phase III Trials of Second-line Treatment for Advanced Gastric or Gastroesophageal Junction Cancer

Popis výsledku v původním jazyce

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 &gt;= 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.

Název v anglickém jazyce

Exposure-Response Analyses of Ramucirumab from Two Randomized, Phase III Trials of Second-line Treatment for Advanced Gastric or Gastroesophageal Junction Cancer

Popis výsledku anglicky

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 &gt;= 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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Molecular Cancer Therapeutics

ISSN

1535-7163

e-ISSN

—

Svazek periodika

16

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

2215-2222

Kód UT WoS článku

000412220900015

EID výsledku v databázi Scopus

2-s2.0-85030683960