Exposure-response relationship of ramucirumab in patients with advanced second-line colorectal cancer: exploratory analysis of the RAISE trial

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F17%3A10373762" target="_blank" >RIV/00216208:11130/17:10373762 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064203:_____/17:10373762 RIV/00209805:_____/17:00077832

Výsledek na webu

<a href="https://doi.org/10.1007/s00280-017-3380-z" target="_blank" >https://doi.org/10.1007/s00280-017-3380-z</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00280-017-3380-z" target="_blank" >10.1007/s00280-017-3380-z</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Exposure-response relationship of ramucirumab in patients with advanced second-line colorectal cancer: exploratory analysis of the RAISE trial

Popis výsledku v původním jazyce

To characterize ramucirumab exposure-response relationships for efficacy and safety in patients with metastatic colorectal cancer (mCRC) using data from the RAISE study. Sparse pharmacokinetic samples were collected; a population pharmacokinetic analysis was conducted. Univariate and multivariate Cox proportional hazards models analyzed the relationship between predicted ramucirumab minimum trough concentration at steady state (C (min,ss)) and survival. Kaplan-Meier analysis was used to evaluate survival from patients in the ramucirumab plus folinic acid, 5-fluorouracil, and irinotecan (FOLFIRI) treatment arm stratified by C (min,ss) quartiles (Q). An ordered categorical model analyzed the relationship between C (min,ss) and safety outcomes. Pharmacokinetic samples from 906 patients were included in exposure-efficacy analyses; samples from 905 patients were included in exposure-safety analyses. A significant association was identified between C (min,ss) and overall survival (OS) and progression-free survival (PFS) (p &lt; 0.0001 for both). This association remained significant after adjusting for baseline factors associated with OS or PFS (p &lt; 0.0001 for both). Median OS was 11.5, 12.9, 16.4, and 16.7, and 12.4 months for ramucirumab C (min,ss) Q1, Q2, Q3, Q4, and placebo group, respectively. Median PFS was 5.4, 4.6, 6.8, 8.5, and 5.2 months for ramucirumab C (min,ss) Q1, Q2, Q3, Q4, and placebo group, respectively. The risk of Grade ae&lt;yen&gt;3 neutropenia was associated with an increase in ramucirumab exposure. Exploratory exposure-response analyses suggested a positive relationship between efficacy and ramucirumab exposure with manageable toxicities in patients from the RAISE study with mCRC over the ranges of exposures achieved by a dose of 8 mg/kg every 2 weeks in combination with FOLFIRI.

Název v anglickém jazyce

Exposure-response relationship of ramucirumab in patients with advanced second-line colorectal cancer: exploratory analysis of the RAISE trial

Popis výsledku anglicky

To characterize ramucirumab exposure-response relationships for efficacy and safety in patients with metastatic colorectal cancer (mCRC) using data from the RAISE study. Sparse pharmacokinetic samples were collected; a population pharmacokinetic analysis was conducted. Univariate and multivariate Cox proportional hazards models analyzed the relationship between predicted ramucirumab minimum trough concentration at steady state (C (min,ss)) and survival. Kaplan-Meier analysis was used to evaluate survival from patients in the ramucirumab plus folinic acid, 5-fluorouracil, and irinotecan (FOLFIRI) treatment arm stratified by C (min,ss) quartiles (Q). An ordered categorical model analyzed the relationship between C (min,ss) and safety outcomes. Pharmacokinetic samples from 906 patients were included in exposure-efficacy analyses; samples from 905 patients were included in exposure-safety analyses. A significant association was identified between C (min,ss) and overall survival (OS) and progression-free survival (PFS) (p &lt; 0.0001 for both). This association remained significant after adjusting for baseline factors associated with OS or PFS (p &lt; 0.0001 for both). Median OS was 11.5, 12.9, 16.4, and 16.7, and 12.4 months for ramucirumab C (min,ss) Q1, Q2, Q3, Q4, and placebo group, respectively. Median PFS was 5.4, 4.6, 6.8, 8.5, and 5.2 months for ramucirumab C (min,ss) Q1, Q2, Q3, Q4, and placebo group, respectively. The risk of Grade ae&lt;yen&gt;3 neutropenia was associated with an increase in ramucirumab exposure. Exploratory exposure-response analyses suggested a positive relationship between efficacy and ramucirumab exposure with manageable toxicities in patients from the RAISE study with mCRC over the ranges of exposures achieved by a dose of 8 mg/kg every 2 weeks in combination with FOLFIRI.

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

Cancer Chemotherapy and Pharmacology

ISSN

0344-5704

e-ISSN

—

Svazek periodika

80

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

10

Strana od-do

599-608

Kód UT WoS článku

000408616700018

EID výsledku v databázi Scopus

2-s2.0-85025828767