Monitoring of plasma concentrations of dabrafenib and trametinib in advanced BRAFV600
Dabrafenib
Drug monitoring
Melanoma
Molecular targeted therapies
Trametinib
Journal
Annales de dermatologie et de venereologie
ISSN: 0151-9638
Titre abrégé: Ann Dermatol Venereol
Pays: France
ID NLM: 7702013
Informations de publication
Date de publication:
Mar 2022
Mar 2022
Historique:
received:
11
12
2020
revised:
28
01
2021
accepted:
14
04
2021
pubmed:
30
6
2021
medline:
23
2
2022
entrez:
29
6
2021
Statut:
ppublish
Résumé
Dabrafenib (D) and trametinib (T) improved survival in patients with BRAFV600 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. We analysed 71 D and 58T assays from 34 patients. High inter-individual variability of PCD (median: 65.0ng/mL; interquartile range (IQR) [4-945]) and of PCT (median: 8.6ng/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±183ng/mL and 9.3±3.6ng/mL, respectively) and responders (complete, partial or stable response) (n=13; 159±225ng/mL, P=0.58 and 10.6±24.4ng/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±4.8ng/mL) than for male subjects (8.8ng/mL±2.9, P=0.01), but no difference was observed between sex and CPD (P=0.32). 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.
Sections du résumé
BACKGROUND
BACKGROUND
Dabrafenib (D) and trametinib (T) improved survival in patients with BRAFV600
METHODS
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
RESULTS
We analysed 71 D and 58T assays from 34 patients. High inter-individual variability of PCD (median: 65.0ng/mL; interquartile range (IQR) [4-945]) and of PCT (median: 8.6ng/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±183ng/mL and 9.3±3.6ng/mL, respectively) and responders (complete, partial or stable response) (n=13; 159±225ng/mL, P=0.58 and 10.6±24.4ng/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±4.8ng/mL) than for male subjects (8.8ng/mL±2.9, P=0.01), but no difference was observed between sex and CPD (P=0.32).
CONCLUSION
CONCLUSIONS
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.
Identifiants
pubmed: 34183171
pii: S0151-9638(21)00054-5
doi: 10.1016/j.annder.2021.04.005
pii:
doi:
Substances chimiques
Imidazoles
0
Oximes
0
Pyridones
0
Pyrimidinones
0
trametinib
33E86K87QN
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
dabrafenib
QGP4HA4G1B
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
32-38Informations de copyright
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