TAT 2020: Trametinib and Low-Dose Dabrafenib in Advanced BRAF V600 Wild-Type Melanoma
Posted: Wednesday, March 25, 2020
In an online poster from the proceedings of the European Society for Medical Oncology (ESMO) Targeted Anticancer Therapies (TAT) Congress 2020 (Abstract 20P), Gil Awada, MD, of UZ Brussels, and colleagues reported no unexpected toxicities with the combination of trametinib and low-dose dabrafenib in patients with advanced BRAF V600 wild-type melanoma, in a phase II trial. “Low-dose dabrafenib is able to prevent trametinib-related skin toxicity,” the investigators stated. “Thus, combining low-dose dabrafenib with trametinib is a safe approach to increase tolerance of and optimize exposure to trametinib.”
A total of nine patients were given trametinib (2 mg once daily), and eight were given trametinib plus low dose dabrafenib (50 mg twice daily). Treatment-related adverse events were seen in 15 patients, with 29% of these side effects being grade 3 or 4. Serious adverse events included hyponatremia, syncope, and pneumonitis.
All nine patients who initiated treatment with trametinib monotherapy developed acneiform, which healed after interruption of treatment followed by the addition of low dose dabrafenib to standard trametinib treatment. In the combination-therapy arm, one patient developed acneiform, which resolved with local therapy. The trametinib dose required reduction in four patients due to the following adverse events: decrease in ventricular ejection fraction, central serous retinopathy, increase in aspartate transaminase/alanine transaminase levels, and hyponatremia/syncope. At the time the abstract was posted, 4 of 15 patients had an unconfirmed response; disease was controlled in 7 of 15 evaluable patients.
Disclosure: For full disclosures of the study authors, visit esmo.org.