Article Dans Une Revue British Journal of Cancer Année : 2024

Exposure-response relationship of cabozantinib in patients with metastatic renal cell carcinoma treated in routine care

Jonathan Chauvin
  • Fonction : Auteur

Résumé

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.

Dates et versions

hal-04821736 , version 1 (05-12-2024)

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Benoit Blanchet, Alexandre Xu-Vuilard, Anne Jouinot, Florent Puisset, David Combarel, et al.. Exposure-response relationship of cabozantinib in patients with metastatic renal cell carcinoma treated in routine care. British Journal of Cancer, 2024, 130 (6), pp.961-969. ⟨10.1038/s41416-024-02585-y⟩. ⟨hal-04821736⟩
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