Pharmacokinetics/Pharmacodynamics of Dabrafenib and Trametinib for Redifferentiation and Treatment of Radioactive Iodine-Resistant Mutated Advanced Differentiated Thyroid Cancer
Authors' conclusion
Our data suggest a relationship between DLT onset and trametinib plasma exposure, as well as an association between achievement of RAI reuptake and dabrafenib plasma exposure (AUC and ratio of AUCOHD/DAB).
Study context
- Population
- Patients with metastatic radioactive iodine (RAI)-resistant mutant DTC treated with dabrafenib and/or trametinib in a redifferentiation strategy, March 2014–December 2021, with plasma concentrations measured15 of 22 included
- Exposure
- Plasma exposure (AUC) to dabrafenib, hydroxy-dabrafenib and trametinib vs dose-limiting toxicity (DLT) onset and RAI reuptake
- Trametinib-related DLTn = 9
- Dabrafenib-related DLTn = 8
- RAI reuptaken = 9
- Outcome
- Last AUCTRA by trametinib-related DLT
Methodological detailsmonocentric, pharmacokinetic/pharmacodynamic
- Monocentric
- Pharmacokinetic/pharmacodynamic
Main finding
As reported in the abstract
Trametinib-related DLT
390
IQR 67 · ng/mL·h-1
No DLT
215
average · IQR 91 · ng/mL·h-1
P = 0.008
Observational data: associations, not effects.
Further findings
| Outcome | Values | P value |
|---|---|---|
| AUCDAB by dabrafenib-related DLTDabrafenib-related DLT vs Other patients · other patients 6953 ng/mL·h-1 | Dabrafenib-related DLT 9265 ng/mL·h-1 | P = 0.09 |
| AUCDAB by RAI reuptakeRAI reuptake vs No RAI reuptake · significantly lower with RAI reuptake | RAI reuptake 6990 ng/mL·h-1 · No RAI reuptake 9764 ng/mL·h-1 | P = 0.014 |
| AUCOHD/DAB relative exposure ratio by RAI reuptakeRAI reuptake vs No RAI reuptake · significantly higher with RAI reuptake | P = 0.0047 |
Clinical and demographic characteristics vs DLT onset
- No clinical and demographical characteristic was associated with DLT onset
Tumor redifferentiation
- Patients with tumor redifferentiation
- 9 of 15 (60%)
Safety
- Dabrafenib-related DLT
- 8 (62%)
- Trametinib-related DLT
- 9 (64%)
Original publication
Pharmacokinetics/Pharmacodynamics of Dabrafenib and Trametinib for Redifferentiation and Treatment of Radioactive Iodine-Resistant Mutated Advanced Differentiated Thyroid Cancer. Thyroid. Published 12 October 2023. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →