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Cerbone L, Combarel D, Geraud A, et al. Association of cabozantinib pharmacokinetics, progression and toxicity in metastatic renal cell carcinoma patients: results from a pharmacokinetics/pharmacodynamics study. ESMO Open. 2021;6(6):100312doi: 10.1016/j.esmoop.2021.100312.
Cerbone, L., Combarel, D., Geraud, A., Auclin, E., Foulon, S., Alves Costa Silva, C., Colomba, E., Carril, L., Derosa, L., Flippot, R., Mir, O., Khoudour, N., Blanchet, B., Escudier, B., Paci, A., & Albiges, L. (2021). Association of cabozantinib pharmacokinetics, progression and toxicity in metastatic renal cell carcinoma patients: results from a pharmacokinetics/pharmacodynamics study. ESMO open, 6(6), 100312. https://doi.org/10.1016/j.esmoop.2021.100312
Cerbone, L, et al. "Association of cabozantinib pharmacokinetics, progression and toxicity in metastatic renal cell carcinoma patients: results from a pharmacokinetics/pharmacodynamics study." ESMO open vol. 6,6 (2021): 100312. doi: https://doi.org/10.1016/j.esmoop.2021.100312
Cerbone L, Combarel D, Geraud A, Auclin E, Foulon S, Alves Costa Silva C, Colomba E, Carril L, Derosa L, Flippot R, Mir O, Khoudour N, Blanchet B, Escudier B, Paci A, Albiges L. Association of cabozantinib pharmacokinetics, progression and toxicity in metastatic renal cell carcinoma patients: results from a pharmacokinetics/pharmacodynamics study. ESMO Open. 2021 Dec;6(6):100312. doi: 10.1016/j.esmoop.2021.100312. Epub 2021 Dec 01. PMID: 34864351; PMCID: PMC8645912.
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ESMO Open. 2021 Dec;6(6):100312. doi: 10.1016/j.esmoop.2021.100312. Epub 2021 Dec 01.

Association of cabozantinib pharmacokinetics, progression and toxicity in metastatic renal cell carcinoma patients: results from a pharmacokinetics/pharmacodynamics study.

ESMO open

L Cerbone, D Combarel, A Geraud, E Auclin, S Foulon, C Alves Costa Silva, E Colomba, L Carril, L Derosa, R Flippot, O Mir, N Khoudour, B Blanchet, B Escudier, A Paci, L Albiges

Affiliations

  1. Department of Oncological Medicine, Gustave Roussy, Villejuif, France.
  2. Department of Medical Biology and Pathology, Gustave Roussy, Villejuif, France; Medical School, University of Paris XI Sacly, Saclay, France.
  3. Medical School, University of Paris XI Sacly, Saclay, France; Department of Therapeutic Innovations and Early Trials, Gustave Roussy, Villejuif, France.
  4. Medical Oncology Hopital Europeen Georges Pompidou, Paris, France.
  5. Department of Biostatistics and Epidemiology, Gustave Roussy, Paris, France.
  6. Functional Unity (UF) Drug Biology and Toxicology Department, Hopital Cochin, Paris, France.
  7. Functional Unity (UF) Drug Biology and Toxicology Department, Hopital Cochin, Paris, France; UMR8038 CNRS, U1268 INSERM, Faculty of Pharmacy, University of Paris, Paris, France.
  8. Department of Oncological Medicine, Gustave Roussy, Villejuif, France; Medical School, University of Paris XI Sacly, Saclay, France. Electronic address: [email protected].

PMID: 34864351 PMCID: PMC8645912 DOI: 10.1016/j.esmoop.2021.100312

Abstract

BACKGROUND: Cabozantinib is a tyrosine kinase inhibitor with a substantial efficacy in metastatic renal cell carcinoma, and is associated with a challenging toxicity profile leading to frequent drug discontinuations. Whereas an exposure/safety relationship was demonstrated for this drug, an exposure/efficacy relationship is still unknown.

PATIENTS AND METHODS: We carried out a monocentric, observational, pharmacokinetics/pharmacodynamics (PK/PD) study in patients with metastatic renal cell carcinoma (INDS MR 5612140520). We used measured blood concentrations of cabozantinib (C

RESULTS: We enrolled 76 patients, including 35 who experienced disease progression and 30 with grade 3-4 toxicity. Patients with progressive disease had a significantly lower median C

CONCLUSION: We first demonstrate the PK/PD relationship for cabozantinib. Severe toxicities are associated with a higher drug exposure, whereas inefficacy is associated with a lower drug exposure. Cabozantinib plasma drug monitoring may be useful to optimize clinical practice.

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Keywords: cabozantinib; dose-exposure; kidney cancer; pharmacokinetics; therapeutic failure; toxicity

Conflict of interest statement

Disclosures EA reports personal financial interest from Genzyme and Mundipharma, outside the submitted work. EC reports personal financial interest from Bristol Myers Squibb (BMS), Brazil Clovis Oncol

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