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

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发表日期：

2024年1月25日

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Benoit Blanchet,
Alexandre Xu-Vuillard,
Anne Jouinot,
Florent Puisset,
David Combarel,
Olivier Huillard,
Félicien Le Louedec,
Fabienne Thomas,
Marcus Teixeira,
Ronan Flippot,
Loic Mourey,
Laurence Albiges,
Thomas Pudlarz,
Charlotte Joly,
Christophe Tournigand,
Jonathan Chauvin,
Alicja Puszkiel,
Etienne Chatelut,
Xavier Decleves,
Michel Vidal,
François Goldwasser,
Stéphane Oudard,
Jacques Medioni,
Yann-Alexandre Vano

摘要

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.