Exposure-response relationship of cabozantinib in patients with metastatic renal cell carcinoma treated in routine care.
Br J Cancer
; 130(6): 961-969, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38272963
ABSTRACT
BACKGROUND:
Interindividual pharmacokinetic variability may influence the clinical benefit or toxicity of cabozantinib in metastatic renal cell carcinoma (mRCC). We aimed to investigate the exposure-toxicity and exposure-response relationship of cabozantinib in unselected mRCC patients treated in routine care.METHODS:
This ambispective multicenter study enrolled consecutive patients receiving cabozantinib in monotherapy. Steady-state trough concentration (Cmin,ss) within the first 3 months after treatment initiation was used for the PK/PD analysis with dose-limiting toxicity (DLT) and survival outcomes. Logistic regression and Cox proportional-hazards models were used to identify the risk factors of DLT and inefficacy in patients, respectively.RESULTS:
Seventy-eight mRCC patients were eligible for the statistical analysis. Fifty-two patients (67%) experienced DLT with a median onset of 2.1 months (95%CI 0.7-8.2). In multivariate analysis, Cmin,ss was identified as an independent risk factor of DLT (OR 1.46, 95%CI [1.04-2.04]; p = 0.029). PFS and OS were not statistically associated with the starting dose (p = 0.81 and p = 0.98, respectively). In the multivariate analysis of PFS, Cmin, ss > 336 ng/mL resulted in a hazard ratio of 0.28 (95%CI, 0.10-0.77, p = 0.014). By contrast, Cmin, ss > 336 ng/mL was not statistically associated with longer OS.CONCLUSION:
Early plasma drug monitoring may be useful to optimise cabozantinib treatment in mRCC patients treated in monotherapy, especially in frail patients starting at a lower than standard dose.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Carcinoma de Células Renales
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Neoplasias Renales
Tipo de estudio:
Clinical_trials
/
Prognostic_studies
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Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Br J Cancer
Año:
2024
Tipo del documento:
Article
País de afiliación:
Francia