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Clinical Pharmacokinetics and Pharmacodynamics of Dabrafenib

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Abstract

Dabrafenib is a potent and selective inhibitor of BRAF-mutant kinase that is approved, as monotherapy or in combination with trametinib (mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor), for unresectable or metastatic BRAF-mutated melanoma, advanced non-small cell lung cancer and anaplastic thyroid cancer harbouring the BRAFV600E mutation. The recommended dose of dabrafenib is 150 mg twice daily (bid) under fasted conditions. After single oral administration of the recommended dose, the absolute oral bioavailability (F) of dabrafenib is 95%. Dabrafenib shows a time-dependent increase in apparent clearance (CL/F) following multiple doses, which is likely due to induction of its own metabolism through cytochrome P450 (CYP) 3A4. Therefore, steady state is reached only after 14 days of daily dose administration. Moreover, the extent of this auto-induction process is dependent on the dose, which explains why dabrafenib systemic exposure at steady state increases less than dose proportionally over the dose range of 75–300 mg bid. The main elimination route of dabrafenib is the oxidative metabolism via CYP3A4/2C8 and biliary excretion. Among the three major metabolites identified, hydroxy-dabrafenib appears to contribute to the pharmacological activity. Age, sex and body weight did not have any clinically significant influence on plasma exposure to dabrafenib. No dose adjustment is needed for patients with mild renal or hepatic impairment, whereas the impacts of severe impairment on dabrafenib pharmacokinetics remain unknown. Considering that dabrafenib is a substrate of CYP3A4/2C8 and is a CYP3A4/2B6/2C inducer, drug–drug interactions are expected with dabrafenib. The relationship between clinical outcomes and plasma exposure to dabrafenib and hydroxy-dabrafenib should be investigated more deeply.

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References

  1. Cargnello M, Roux PP. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev. 2011;75:50–83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417:949–54.

    Article  PubMed  CAS  Google Scholar 

  3. Long GV, Menzies AM, Nagrial AM, Haydu LE, Hamilton AL, Mann GJ, et al. Prognostic and clinicopathologic associations of oncogenic BRAF in metastatic melanoma. J Clin Oncol. 2011;29:1239–46.

    Article  PubMed  Google Scholar 

  4. Summary of product characteristics: Tafinlar (dabrafenib); 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002604/WC500149671.pdf. Accessed 13 Feb 2018.

  5. Tafinlar FDA label; 2013. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/202806s010lbl.pdf. Accessed 9 Jun 2018.

  6. Hauschild A, Grob J-J, Demidov LV, Jouary T, Gutzmer R, Millward M, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380:358–65.

    Article  PubMed  CAS  Google Scholar 

  7. Long GV, Flaherty KT, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, et al. Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/K-mutant melanoma: long-term survival and safety analysis of a phase 3 study. Ann Oncol. 2017;28:1631–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Corcoran RB, Atreya CE, Falchook GS, Kwak EL, Ryan DP, Bendell JC, et al. Combined BRAF and MEK inhibition with dabrafenib and trametinib in BRAF V600-mutant colorectal cancer. J Clin Oncol. 2015;33:4023–31.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Johanns TM, Ferguson CJ, Grierson PM, Dahiya S, Ansstas G. Rapid clinical and radiographic response with combined dabrafenib and trametinib in adults with BRAF-mutated high-grade glioma. J Natl Compr Cancer Netw. 2018;16:4–10.

    Article  Google Scholar 

  10. FDA Center for Drug Evaluation and Research (CDER). Dabrafenib clinical pharmacology and biopharmaceutics review; 2013. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/202806Orig1s000ClinPharmR.pdf. Accessed 12 Feb 2018.

  11. European Medicines Agency. Committee for Medicinal Products for Human Use (CHMP) assessment report: Tafinlar (dabrafenib); 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/002604/WC500149673.pdf. Accessed 7 Jan 2018.

  12. FDA Biopharmaceutics Classification System (BCS) guidance. https://www.fda.gov/downloads/Drugs/Guidances/ucm070246.pdf. Accessed 29 July 2018.

  13. Ouellet D, Grossmann KF, Limentani G, Nebot N, Lan K, Knowles L, et al. Effects of particle size, food, and capsule shell composition on the oral bioavailability of dabrafenib, a BRAF inhibitor, in patients with BRAF mutation-positive tumors. J Pharm Sci. 2013;102:3100–9.

    Article  PubMed  CAS  Google Scholar 

  14. Rheault TR, Stellwagen JC, Adjabeng GM, Hornberger KR, Petrov KG, Waterson AG, et al. Discovery of dabrafenib: a selective inhibitor of Raf kinases with antitumor activity against B-Raf-driven tumors. ACS Med Chem Lett. 2013;4:358–62.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. King AJ, Arnone MR, Bleam MR, Moss KG, Yang J, Fedorowicz KE, et al. Dabrafenib; preclinical characterization, increased efficacy when combined with trametinib, while BRAF/MEK tool combination reduced skin lesions. PLoS One. 2013;8:e67583.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Laquerre S, Arnone M, Moss K, Yang J, Fisher K, Kane-Carson LS, et al. A selective Raf kinase inhibitor induces cell death and tumor regression of human cancer cell lines encoding B-RafV600E mutation [abstract no. B88]. Mol Cancer Ther. 2009;8(12 Suppl):B88.

    Article  Google Scholar 

  17. Gentilcore G, Madonna G, Mozzillo N, Ribas A, Cossu A, Palmieri G, et al. Effect of dabrafenib on melanoma cell lines harbouring the BRAF(V600D/R) mutations. BMC Cancer. 2013;13:17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Carnahan J, Beltran PJ, Babij C, Le Q, Rose MJ, Vonderfecht S, et al. Selective and potent Raf inhibitors paradoxically stimulate normal cell proliferation and tumor growth. Mol Cancer Ther. 2010;9:2399–410.

    Article  PubMed  CAS  Google Scholar 

  19. Hatzivassiliou G, Song K, Yen I, Brandhuber BJ, Anderson DJ, Alvarado R, et al. RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature. 2010;464:431–5.

    Article  PubMed  CAS  Google Scholar 

  20. Heidorn SJ, Milagre C, Whittaker S, Nourry A, Niculescu-Duvas I, Dhomen N, et al. Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell. 2010;140:209–21.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Poulikakos PI, Zhang C, Bollag G, Shokat KM, Rosen N. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature. 2010;464:427–30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Holderfield M, Merritt H, Chan J, Wallroth M, Tandeske L, Zhai H, et al. RAF inhibitors activate the MAPK pathway by relieving inhibitory autophosphorylation. Cancer Cell. 2013;23:594–602.

    Article  PubMed  CAS  Google Scholar 

  23. Chapman PB, Hauschild A, Robert C, Haanen JB, Ascierto P, Larkin J, et al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011;364:2507–16.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med. 2010;363:809–19.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Dubauskas Z, Kunishige J, Prieto VG, Jonasch E, Hwu P, Tannir NM. Cutaneous squamous cell carcinoma and inflammation of actinic keratoses associated with sorafenib. Clin Genitourin Cancer. 2009;7:20–3.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Bershas DA, Ouellet D, Mamaril-Fishman DB, Nebot N, Carson SW, Blackman SC, et al. Metabolism and disposition of oral dabrafenib in cancer patients: proposed participation of aryl nitrogen in carbon-carbon bond cleavage via decarboxylation following enzymatic oxidation. Drug Metab Dispos. 2013;41:2215–24.

    Article  PubMed  CAS  Google Scholar 

  27. Menzies A, Long G, Murali R. Dabrafenib and its potential for the treatment of metastatic melanoma. Drug Des Dev Ther. 2012;6:391–405.

    CAS  Google Scholar 

  28. Menzies AM, Kefford RF, Long GV. Paradoxical oncogenesis: are all BRAF inhibitors equal? Pigment Cell Melanoma Res. 2013;26:611–5.

    Article  PubMed  CAS  Google Scholar 

  29. Flaherty KT, Infante JR, Daud A, Gonzalez R, Kefford RF, Sosman J, et al. Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med. 2012;367:1694–703.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, et al. Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial. Lancet. 2015;386:444–51.

    Article  PubMed  CAS  Google Scholar 

  31. Grob JJ, Amonkar MM, Karaszewska B, Schachter J, Dummer R, Mackiewicz A, et al. Comparison of dabrafenib and trametinib combination therapy with vemurafenib monotherapy on health-related quality of life in patients with unresectable or metastatic cutaneous BRAF Val600-mutation-positive melanoma (COMBI-v): results of a phase 3, open-l. Lancet Oncol. 2015;16:1389–98.

    Article  PubMed  CAS  Google Scholar 

  32. Long GV, Hauschild A, Santinami M, Atkinson V, Mandalà M, Chiarion-Sileni V, et al. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med. 2017;377:1813–23.

    Article  PubMed  CAS  Google Scholar 

  33. Planchard D, Kim TM, Mazieres J, Quoix E, Riely G, Barlesi F, et al. Dabrafenib in patients with BRAFV600E-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016;17:642–50.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Planchard D, Besse B, Groen HJM, Souquet P-J, Quoix E, Baik CS, et al. Dabrafenib plus trametinib in patients with previously treated BRAF V600E -mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol. 2016;17:984–93.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Planchard D, Smit EF, Groen HJM, Mazieres J, Besse B, Helland Å, et al. Dabrafenib plus trametinib in patients with previously untreated BRAF V600E -mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol. 2017;18:1307–16.

    Article  PubMed  CAS  Google Scholar 

  36. Subbiah V, Kreitman RJ, Wainberg ZA, Cho JY, Schellens JHM, Soria JC, et al. Dabrafenib and trametinib treatment in patients with locally advanced or metastatic BRAF V600-mutant anaplastic thyroid cancer. J Clin Oncol. 2018;36:7–13.

    Article  PubMed  CAS  Google Scholar 

  37. Long GV, Trefzer U, Davies MA, Kefford RF, Ascierto PA, Chapman PB, et al. Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13:1087–95.

    Article  PubMed  CAS  Google Scholar 

  38. Falchook GS, Long GV, Kurzrock R, Kim KB, Arkenau TH, Brown MP, et al. Dabrafenib in patients with melanoma, untreated brain metastases, and other solid tumours: a phase 1 dose-escalation trial. Lancet. 2012;379:1893–901.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Davies MA, Saiag P, Robert C, Grob J-J, Flaherty KT, Arance A, et al. Dabrafenib plus trametinib in patients with BRAFV600-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial. Lancet Oncol. 2017;18:863–73.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Carlos G, Anforth R, Clements A, Menzies AM, Carlino MS, Chou S, et al. Cutaneous toxic effects of BRAF inhibitors alone and in combination with MEK inhibitors for metastatic melanoma. JAMA Dermatol. 2015;151:1103–9.

    Article  PubMed  Google Scholar 

  41. Flaherty KT, Robert C, Hersey P, Nathan P, Garbe C, Milhem M, et al. Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med. 2012;367:107–14.

    Article  PubMed  CAS  Google Scholar 

  42. Falchook GS, Long GV, Kurzrock R, Kim KB, Arkenau H-T, Brown MP, et al. Dose selection, pharmacokinetics, and pharmacodynamics of BRAF inhibitor dabrafenib (GSK2118436). Clin Cancer Res. 2014;20:4449–58.

    Article  PubMed  CAS  Google Scholar 

  43. Denton CL, Minthorn E, Carson SW, Young GC, Richards-Peterson LE, Botbyl J, et al. Concomitant oral and intravenous pharmacokinetics of dabrafenib, a BRAF inhibitor, in patients with BRAF V600 mutation-positive solid tumors. J Clin Pharmacol. 2013;53:955–61.

    Article  PubMed  CAS  Google Scholar 

  44. Suttle AB, Grossmann KF, Ouellet D, Richards-Peterson LE, Aktan G, Gordon MS, et al. Assessment of the drug interaction potential and single- and repeat-dose pharmacokinetics of the BRAF inhibitor dabrafenib. J Clin Pharmacol. 2015;55:392–400.

    Article  PubMed  CAS  Google Scholar 

  45. Fujiwara Y, Yamazaki N, Kiyohara Y, Yoshikawa S, Yamamoto N, Tsutsumida A, et al. Safety, tolerability, and pharmacokinetic profile of dabrafenib in Japanese patients with BRAF V600 mutation-positive solid tumors: a phase 1 study. Investig New Drugs. 2018;36:259–68.

    Article  CAS  Google Scholar 

  46. Ouellet D, Gibiansky E, Leonowens C, O’Hagan A, Haney P, Switzky J, et al. Population pharmacokinetics of dabrafenib, a BRAF inhibitor: effect of dose, time, covariates, and relationship with its metabolites. J Clin Pharmacol. 2014;54:696–706.

    Article  PubMed  CAS  Google Scholar 

  47. Mittapalli RK, Vaidhyanathan S, Dudek AZ, Elmquist WF. Mechanisms limiting distribution of the threonine-protein kinase B-RaF(V600E) inhibitor dabrafenib to the brain: implications for the treatment of melanoma brain metastases. J Pharmacol Exp Ther. 2013;344:655–64.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Qiu J-G, Zhang Y-J, Li Y, Zhao J-M, Zhang W-J, Jiang Q-W, et al. Trametinib modulates cancer multidrug resistance by targeting ABCB1 transporter. Oncotarget. 2015;6:15494–509.

    PubMed  PubMed Central  Google Scholar 

  49. Vaidhyanathan S, Mittapalli RK, Sarkaria JN, Elmquist WF. Factors influencing the CNS distribution of a novel MEK-1/2 inhibitor: implications for combination therapy for melanoma brain metastases. Drug Metab Dispos. 2014;42:1292–300.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Ascierto PA, Minor D, Ribas A, Lebbe C, O’Hagan A, Arya N, et al. Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. J Clin Oncol. 2013;31:3205–11.

    Article  PubMed  CAS  Google Scholar 

  51. Rousset M, Dutriaux C, Bosco-Lévy P, Prey S, Pham-Ledard A, Dousset L, et al. Trough dabrafenib plasma concentrations can predict occurrence of adverse events requiring dose reduction in metastatic melanoma. Clin Chim Acta. 2017;472:26–9.

    Article  PubMed  CAS  Google Scholar 

  52. Park JJ, Boddy AV, Liu X, Harris D, Lee V, Kefford RF, et al. Pharmacokinetics of dabrafenib in a patient with metastatic melanoma undergoing haemodialysis. Pigment Cell Melanoma Res. 2017;30:68–71.

    Article  PubMed  CAS  Google Scholar 

  53. Novartis Pharmaceuticals. Pharmacokinetics of dabrafenib in subjects with hepatic impairment [ClinicalTrials.gov identifier NCT02873650]. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02873650. Accessed 13 Feb 2018.

  54. Lawrence SK, Nguyen D, Bowen C, Richards-Peterson L, Skordos KW. The metabolic drug–drug interaction profile of Dabrafenib: in vitro investigations and quantitative extrapolation of the P450-mediated DDI risk. Drug Metab Dispos. 2014;42:1180–90.

    Article  PubMed  CAS  Google Scholar 

  55. Suttle B, Grossmann K, Richards-Peterson L, Ouellet D, Aktan G, Gordon M, et al. A study of the effects of inhibition of CYP3A4 BY ketoconazole (K) and CYP2C8 by gemfibrozil (G) on the pharmacokinetics dabrafenib (D).: PII-085. Clin Pharmacol Ther. 2014;95:S89–90.

    Google Scholar 

  56. van Leeuwen RWF, Jansman FGA, Hunfeld NG, Peric R, Reyners AKL, Imholz ALT, et al. Tyrosine kinase inhibitors and proton pump inhibitors: an evaluation of treatment options. Clin Pharmacokinet. 2017;56:683–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Levavasseur M, Darras S, Mortier L, Goeminne C, Auffret M, Bertrand M. Drug interaction between dabrafenib and immunosuppressive drugs: about one case. Melanoma Res. 2016;26:532–4.

    Article  PubMed  CAS  Google Scholar 

  58. Long GV, Grob J-J, Nathan P, Ribas A, Robert C, Schadendorf D, et al. Factors predictive of response, disease progression, and overall survival after dabrafenib and trametinib combination treatment: a pooled analysis of individual patient data from randomised trials. Lancet Oncol. 2016;17:1743–54.

    Article  PubMed  CAS  Google Scholar 

  59. Schadendorf D, Long GV, Stroiakovski D, Karaszewska B, Hauschild A, Levchenko E, et al. Three-year pooled analysis of factors associated with clinical outcomes across dabrafenib and trametinib combination therapy phase 3 randomised trials. Eur J Cancer. 2017;82:45–55.

    Article  PubMed  CAS  Google Scholar 

  60. Menzies AM, Ashworth MT, Swann S, Kefford RF, Flaherty K, Weber J, et al. Characteristics of pyrexia in BRAFV600E/K metastatic melanoma patients treated with combined dabrafenib and trametinib in a phase I/II clinical trial. Ann Oncol. 2015;26:415–21.

    Article  PubMed  CAS  Google Scholar 

  61. Yang S-K, Hong M, Baek J, Choi H, Zhao W, Jung Y, et al. A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia. Nat Genet. 2014;46:1017–20.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Yip VLM, Alfirevic A, Pirmohamed M. Genetics of immune-mediated adverse drug reactions: a comprehensive and clinical review. Clin Rev Allergy Immunol. 2015;48:165–75.

    Article  PubMed  CAS  Google Scholar 

  63. Kulkarni D, Song K, Briley L, King K, Dabrowski C, Mookerjee B, et al. Pyrexia in dabrafenib-treated melanoma patients is not associated with common genetic variation or HLA polymorphisms. Pharmacogenomics. 2016;17:459–62.

    Article  PubMed  CAS  Google Scholar 

  64. Nebot N, Arkenau HTT, Infante JR, Chandler JC, Weickhardt A, Lickliter JD, et al. Evaluation of the effect of dabrafenib and metabolites on QTc interval in patients with BRAF V600-mutant tumours. Br J Clin Pharmacol. 2018;84:764–75.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  65. Verheijen RB, Yu H, Schellens JHM, Beijnen JH, Steeghs N, Huitema ADR. Practical recommendations for therapeutic drug monitoring of kinase inhibitors in oncology. Clin Pharmacol Ther. 2017;102:765–76.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372:30–9.

    Article  PubMed  CAS  Google Scholar 

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Author notes

  1. Alicja Puszkiel and Gaëlle Noé contributed equally to this work.

Authors and Affiliations

  1. Cancer Research Center of Toulouse (CRCT), Inserm U1037, Université Paul Sabatier, Toulouse, France

    Alicja Puszkiel, Marie-Noëlle Paludetto & Etienne Chatelut

  2. Department of Pharmacology and Toxicology, Bicetre Hospital, AP-HP, Kremlin Bicetre, France

    Gaëlle Noé

  3. Department of Medical Oncology, CERIA, CARPEM, Cochin University Hospital, APHP, 75014, Paris, France

    Audrey Bellesoeur & François Goldwasser

  4. Multidisciplinary Risk Assessment and Drug Monitoring Unit, CERIA, CARPEM, Cochin University Hospital, AP-HP, 75014, Paris, France

    Audrey Bellesoeur & Audrey Thomas-Schoemann

  5. Department of Dermatology, Cochin University Hospital, AP-HP, 75014, Paris, France

    Nora Kramkimel

  6. Department of Pharmacy, Institut Universitaire du Cancer de Toulouse - Oncopole, Toulouse, France

    Marie-Noëlle Paludetto

  7. UMR8638 CNRS, Faculty of Pharmacy, University Paris Descartes, PRES Sorbonne Paris Cité, Paris, France

    Audrey Thomas-Schoemann, Michel Vidal & Benoit Blanchet

  8. Department of Pharmacokinetics and Pharmacochemistry, CERIA, CARPEM, Cochin University Hospital, AP-HP, 27 rue du Faubourg Saint Jacques, 75014, Paris, France

    Michel Vidal & Benoit Blanchet

  9. Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole, Toulouse, France

    Etienne Chatelut

  10. Groupe de Pharmacologie Clinique Oncologique (GPCO), Paris, France

    Etienne Chatelut & Benoit Blanchet

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  1. Alicja Puszkiel
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Alicja Puszkiel, Gaëlle Noé, Audrey Bellesoeur, Nora Kramkimel, Marie-Noëlle Paludetto, Audrey Thomas-Schoemann, Michel Vidal, François Goldwasser, Etienne Chatelut and Benoit Blanchet declare that they have no conflicts of interest to disclose.

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Puszkiel, A., Noé, G., Bellesoeur, A. et al. Clinical Pharmacokinetics and Pharmacodynamics of Dabrafenib. Clin Pharmacokinet 58, 451–467 (2019). https://doi.org/10.1007/s40262-018-0703-0

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