medwireNews: Adjuvant combination therapy with the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib halves the risk for relapse in patients with stage III melanoma with BRAF V600E or V600K mutations, show results from the COMBI-AD trial.
The trial was presented at the ESMO 2017 Congress in Madrid, Spain, and published in The New England Journal of Medicine.
At a median follow-up of 2.8 years, 166 (38%) of 438 patients randomly assigned to receive 12 months of combination therapy with dabrafenib 150 mg twice daily plus trametinib 2 mg once daily had experienced disease recurrence or died. This compared with 248 (57%) of 432 patients randomly assigned to receive placebo, giving a significant risk reduction of 53%.
An overall survival benefit was also seen with the combination therapy, compared with placebo, with estimated 3-year rates of 86% and 77%, respectively.
Study co-author Axel Hauschild, from the University of Kiel in Germany, said in a statement to the press: “These are the best results ever shown for an adjuvant treatment in stage III melanomas.”
“Combination treatment with dabrafenib and trametinib more than doubled the relapse-free survival time compared to placebo and the improvement in overall survival was impressive, too.”
However, in the published paper, lead author Georgina Long (University of Sydney, New South Wales, Australia) and colleagues note that although the hazard ratio for death with combination therapy versus placebo was 0.57 with a p-value of 0.0006, “the between-group difference was not statistically significant because it did not cross the prespecified conservative interim boundary of P=0.000019.”
The researchers also report that combination therapy resulted in higher rates of distant metastasis-free survival and freedom from relapse than placebo, with “clinically meaningful” risk reductions of 49% and 53%, respectively.
Nearly all (97%) patients receiving combination therapy had at least one adverse event of any kind and 41% had a serious (grade 3/4) adverse event, most commonly pyrexia, fatigue, and nausea. This compared with a respective 88% and 14% of those receiving placebo.
Adverse events leading to treatment discontinuation occurred in 26% of patients in the combination therapy group and 3% of those in the placebo group.
“The number of treatment discontinuations was a little higher than in trials on stage IV melanoma patients,” said Hauschild. “This could be because 90% of patients had no progressive disease and were treated for the scheduled full year. The longer patients receive treatment, the more likely they are to have adverse events. But there were no new toxicities compared to those already seen in stage IV disease and overall we can say the treatment was well tolerated.”
Hauschild believes that the COMBI-AD trial results are “practice changing.”
He commented: “The combination of dabrafenib and trametinib is a new and very effective adjuvant treatment option in high-risk melanoma patients.”
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare. © 2017 Springer Healthcare part of the Springer Nature group
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