1. Monitoring of plasma concentrations of dabrafenib and trametinib in advanced BRAFV600 melanoma patients
- Author
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Jean-Claude Alvarez, Elisa Funck-Brentano, Philippe Saiag, A. Beauchet, Christian Funck-Brentano, and M. Raynal
- Subjects
Trametinib ,medicine.medical_specialty ,business.industry ,Melanoma ,Hazard ratio ,Dabrafenib ,Dermatology ,medicine.disease ,Gastroenterology ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Interquartile range ,Internal medicine ,Plasma concentration ,otorhinolaryngologic diseases ,medicine ,business ,Adverse effect ,Body mass index ,medicine.drug - 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.
- Published
- 2022