Time-to-Event Modeling of Peripheral Neuropathy: Platform Analysis of Eight Valine-Citrulline-Monomethylauristatin E Antibody-Drug Conjugates.
CPT Pharmacometrics Syst Pharmacol
; 8(8): 606-615, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-31207190
ABSTRACT
Peripheral neuropathy (PN) is a common long-term debilitating toxicity of antimicrotubule agents. PN was the most frequent adverse event resulting in dose modifications and/or discontinuation of treatment for valine-citrulline-monomethylauristatin E antibody-drug conjugates (ADCs) developed at Genentech. A pooled time-to-event analysis across eight ADCs (~700 patients) was performed to evaluate the relationship between the ADC exposure and the risk for developing a clinically significant (grade ≥ 2) PN. In addition, the impact of demographic and pathophysiological risk factors on the risk for PN was explored. The time-to-event analysis suggested that the development of PN risk increased with ADC exposure, treatment duration, body weight, and previously reported PN. This model can be used to inform clinical strategies such as adaptations to dosing regimen and/or treatment duration as well as inform clinical eligibility to reduce the incidence of grade ≥ 2 PN.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
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Doenças do Sistema Nervoso Periférico
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Imunoconjugados
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Neoplasias
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
CPT Pharmacometrics Syst Pharmacol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA