Combination trametinib and dabrafenib show fewer side effects for metastatic melanoma than dabrafenib alone

1. In patients undergoing treatment for metastatic melanoma, there was a statistically significant decreased risk of cutaneous toxic effects in those patients who were treated with combination trametinib and dabrafenib (CombiDT) as compared to dabrafenib alone.

Evidence Rating Level: 2 (Good)

Study Rundown: In the last decade, multiple new medications were created that have vastly improved the prognosis of patients with late-stage melanoma. Namely, BRAF inhibitors dabrafenib and vemurafenib, as well as MEK inhibitors such as trametinib, all have shown a survival benefit. Furthermore, a combination formulation of these drugs, CombiDT, showed superior survival benefit. There has been some evidence that as compared to monotherapy CombiDT also decreases the risk of adverse cutaneous side effects. Authors in this study confirmed this via direct comparison of patients with monotherapy vs. CombiDT. This study was the first of its kind to directly prove these findings, though the findings are limited by the retrospective study design.

Click to read the study in JAMA Dermatology

Relevant Reading: Multiple BRAF Wild-Type Melanomas during Dabrafenib Treatment for Metastatic BRAF-Mutant Melanoma

In-Depth [retrospective cohort]: One hundred and eighty five patients with unresectable stage IIIC and IV melanoma who were treated with BRAF inhibitors vemurafenib (n=36), dabrafenib (n=119), or CombiDT (n=30) therapy were selected retrospectively for inclusion. There were no statistically significant differences in treatment duration between treatment groups, although those patients treated with vemurafenib monotherapy were significantly older than those treated with dabrafenib (60 vs. 53 years old, p=0.045). The most common cutaneous adverse effect in patients while on monotherapy with dabrafenib or vemurafenib was Grover disease (51 patients [42.9%] and 14 [38.9%], respectively [P = .67]), plantar hyperkeratosis (47 [39.5%] and 14 [38.9%], respectively [P = .95]), verrucal keratosis (79 [66.4%] and 26 [72.2%], respectively [P = .51]), and cutaneous squamous cell carcinoma (31 [26.1%] and 13 [36.1%], respectively [P = .54]). As compared to dabrafenib, CombiDT therapy showed a statistically significant decrease in cutaneous squamous cell carcinoma (0 vs 31 [26.1%]; P < .001), verrucal keratosis (0 vs 79 [66.4%]; P < .001), and Grover disease (0 vs 51 [42.9%]; P < .001), albeit a higher frequency of folliculitis (12 patients [40.0%] vs 8 [6.7%]; P < .001).

Image: PD

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