Talazoparib Exposure-Efficacy Analysis in Patients With Advanced Breast Cancer and Germline BRCA1/2 Mutations in the EMBRACA Trial.
J Clin Pharmacol
; 60(10): 1324-1333, 2020 10.
Article
en En
| MEDLINE
| ID: mdl-32468579
ABSTRACT
In the phase 3 EMBRACA trial, treatment with the poly(ADP-ribose) polymerase inhibitor, talazoparib, led to significantly improved progression-free survival (PFS) compared with chemotherapy (hazard ratio, 0.54; 95% confidence interval, 0.41-0.71; P < .0001). We conducted an exposure-efficacy analysis using EMBRACA data from 285 patients who were treated with talazoparib and had available pharmacokinetic parameters to evaluate the effect of talazoparib exposure (time-varying average talazoparib concentration [Cavg,t ]) and other baseline variables on PFS. Graphical examination of the relationship between Cavg,t and PFS and a Cox proportional model were used. Exposure-response analyses showed that higher talazoparib exposure, absence of visceral disease, lower baseline lactate dehydrogenase levels, and disease-free interval >12 months were independent covariates associated with longer PFS. The association of talazoparib exposure with PFS (higher exposure, longer PFS) suggests the recommended starting dose of 1 mg once daily (the maximum tolerated dose) is appropriate.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ftalazinas
/
Neoplasias de la Mama
/
Mutación de Línea Germinal
/
Inhibidores de Poli(ADP-Ribosa) Polimerasas
/
Antineoplásicos
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
Límite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Middle aged
Idioma:
En
Revista:
J Clin Pharmacol
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos