Monitoring of plasma concentrations of dabrafenib and trametinib in advanced BRAFV600mut melanoma patients - Infection et Inflammation Access content directly
Journal Articles Annales de Dermatologie et de Vénéréologie Year : 2022

Monitoring of plasma concentrations of dabrafenib and trametinib in advanced BRAFV600mut melanoma patients

Abstract

Background: Dabrafenib (D) and trametinib (T) improved survival in patients with BRAFV600mut melanoma. High plasma concentration of D (PCD) is weakly associated with adverse events (AE). We investigated the relationship between PCD/T and tumour control or AE. Methods: We analysed PCD/T in patients treated with D + T for metastatic melanoma. We collected data of tumour response (RECIST 1.1) and AE (CTCAE 4.0) blinded to PCD/T results. Results: We analysed 71 D and 58T assays from 34 patients. High inter-individual variability of PCD (median: 65.0 ng/mL; interquartile range (IQR) [4–945]) and of PCT (median: 8.6 ng/mL; IQR [5–39]) was observed. We found a weak relationship between PCD and progression-free survival, taking follow-up time into account (hazard ratio 0.991; 95%CI, 0.981 to 1.000; P = 0.06). However, no difference was observed between mean PCD/T of progressing patients (n = 21; 125 ± 183 ng/mL and 9.3 ± 3.6 ng/mL, respectively) and responders (complete, partial or stable response) (n = 13; 159 ± 225 ng/mL, P = 0.58 and 10.6 ± 24.4 ng/mL, P = 0.29, respectively). No significant relationship was found between PCD/T and most common AEs (fever, lymphopenia, CPK increase, and hepatic cytolysis), body mass index, or age. Mean CPT (n = 16) was significantly higher for female subjects (n = 18; 11.5 ± 4.8 ng/mL) than for male subjects (8.8 ng/mL ± 2.9, P = 0.01), but no difference was observed between sex and CPD (P = 0.32). Conclusion: Our study showed a weak relationship between PCD and progression-free survival, but no relationship between PCD/T and AE was found. Monitoring PCD and PCT alone is unlikely to be useful in assessing response to treatment.
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hal-03604074 , version 1 (22-07-2024)

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M. Raynal, Jean Claude Alvarez, Phillippe Saiag, Alain Beauchet, Christian Funck-Brentano, et al.. Monitoring of plasma concentrations of dabrafenib and trametinib in advanced BRAFV600mut melanoma patients. Annales de Dermatologie et de Vénéréologie, 2022, 149 (1), pp.32-38. ⟨10.1016/j.annder.2021.04.005⟩. ⟨hal-03604074⟩
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