Exposure-response relationship of ramucirumab in patients with advanced second-line colorectal cancer: exploratory analysis of the RAISE trial
The result's identifiers
Result code in 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>
Alternative codes found
RIV/00064203:_____/17:10373762 RIV/00209805:_____/17:00077832
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Exposure-response relationship of ramucirumab in patients with advanced second-line colorectal cancer: exploratory analysis of the RAISE trial
Original language description
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 < 0.0001 for both). This association remained significant after adjusting for baseline factors associated with OS or PFS (p < 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<yen>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.
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
Cancer Chemotherapy and Pharmacology
ISSN
0344-5704
e-ISSN
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Volume of the periodical
80
Issue of the periodical within the volume
3
Country of publishing house
DE - GERMANY
Number of pages
10
Pages from-to
599-608
UT code for WoS article
000408616700018
EID of the result in the Scopus database
2-s2.0-85025828767