By Shreeya Nanda, Senior medwireNews Reporter
Updated results from the COMBI-v trial show significantly improved overall and progression-free survival (OS, PFS) with first-line dabrafenib plus trametinib compared with vemurafenib in patients with advanced melanoma.
The findings of the phase III trial comprising patients with BRAF V600E/K mutation-positive unresectable or metastatic melanoma were presented at the European Cancer Congress in Vienna, Austria, by Caroline Robert, from the Institut Gustave Roussy in Paris, France.
A previous interim analysis with a median follow-up of 11 months showed a significant improvement in OS with dabrafenib and trametinib, explained Robert in her presentation, so much so that the trial was terminated early and patients in the vemurafenib group were allowed to crossover.
In this most recent analysis, the 352 patients randomly assigned to receive the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib had a median OS of 25.6 months. This was not only significantly longer than the 18.0 months observed for the 352 participants given the BRAF inhibitor vemurafenib, but also the “longest ever reached” in a randomised phase III trial in this patient population, said Robert.
And after a median follow-up of 19 months, the 2-year survival rate was significantly higher for the dabrafenib plus trametinib group than for the vemurafenib group, at 51% versus 38%.
Median PFS was also significantly longer, with corresponding times of 12.6 and 7.3 months, and overall response rate and duration of response were similarly improved in the dual therapy compared with the monotherapy arm, at 66% versus 53% and 13.8 versus 8.5 months, respectively.
The incidence of all-grade adverse events continued to be high during the additional follow-up period, with pyrexia (55%) most common in the combination group and arthralgia (52%) in the vemurafenib group, but Robert said this was not surprising.
She added that the percentage of patients who discontinued treatment owing to toxicity was not too different from the proportion noted in the interim analysis, at 16% for the dabrafenib plus trametinib arm (13% at the interim analysis) and 14% for the vemurafenib arm (12% at the interim analysis).
The presenting author concluded that their results, together with those from the COMBI-d phase III trial comparing the dabrafenib and trametinib combination against single-agent dabrafenib, support the use of dabrafenib plus trametinib as “a standard of care therapy in patients with BRAF V600-mutant melanoma”.
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