Melanoma Coverage from Every Angle

Triplet Regimen for BRAF-Mutated Metastatic Melanoma

By: Cordi Craig
Posted: Monday, December 2, 2019

Triplet therapy with nivolumab, dabrafenib, and trametinib appears to be well tolerated in patients with BRAF-mutated metastatic melanoma who are resistant to PD-1 inhibitors or have untreated brain metastases, according to the phase II TRIDeNT study presented at the European Society for Medical Oncology (ESMO) Congress 2019 in Barcelona (Abstract 1312PD). Hussein A. Tawbi, MD, PhD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues measured overall response rates to evaluate the safety and efficacy of this combinatorial approach after patients failed to respond to targeted therapies and immunotherapies. The report was simultaneously published in Annals of Oncology.

In the single-arm trial, investigators treated 24 patients with BRAF-mutated, unresectable stage III or IV metastatic melanoma with nivolumab, dabrafenib, and trametinib. Of those patients, 18 were PD-1–refractory and 6 discontinued treatment due to toxicities. Of the patients who were PD-1–refractory, seven had untreated brain metastases.

A total of 19 of the 24 patients were evaluated at the time of the ESMO presentation. The overall response rate was 89%—15 patients achieved partial responses and 2 patients achieved complete responses. The overall response rate among the 12 evaluable patients with PD-1–refractory disease was 67%, with 2 patients achieving a complete response and 10 achieving a partial response.

According to the authors, nivolumab, dabrafenib, and trametinib may prove to be an effective clinical option for treating patients with immunotherapy-refractory disease and brain metastases. “Further investigation into the correlatives and mechanisms of action is warranted,” they concluded.

 Disclosure: The study authors’ disclosure information may be found at

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