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The risk of relapse dropped 53 percent when trametinib and dabrafenib were used after therapy.
A new combination drug treatment for stage 3 melanoma has shown dramatic promise in extending survival, according to a study presented at an international cancer conference in Spain.
Adjuvant treatment with dabrafenib and trametinib reduced the risk of relapse or death by 53 percent, compared with placebo for patients with BRAF-mutant stage 3 melanoma, according to findings from the phase 3 COMBI-AD study. The work was presented at the 2017 ESMO Congress in Madrid and simultaneously published in the New England Journal of Medicine.
After a median follow-up of 2.8 years, the three-year relapse-free survival (RFS) rate with dabrafenib and trametinib was 58 percent, compared with 39 percent for placebo. Early data for overall survival (OS) showed that 86 percent of patients in the combination arm were alive at three years versus 77 percent with placebo.
“For overall survival, there was a 43 percent reduction in the risk of dying from metastatic melanoma,” said lead investigator Axel Hauschild, M.D., professor of dermatology, University of Kiel, Kiel, Germany.
He called the improvement “a very impressive result that is maintained over time.”
The study included 870 patients, 438 of them received dabrafenib plus trametinib, while 432 received a placebo.
All patients were within 12 weeks of surgery. Dabrafenib was given at 150 mg twice daily with trametinib at 2 mg once daily for 12 months.
The baseline characteristics were similar between groups. In the combination arm, the median age of patients was 50 years and 91 percent of tumors had the BRAF V600E mutation with the remainder having the V600K alteration.
The median RFS was not reached with the combination versus 16.6 months for placebo. RFS was improved with dabrafenib/trametinib across all subgroups, Hauschild noted. "There was not a single outlier,” he noted. “All three stages benefited from the combination in the same way.”
The one-year OS rates were 97 percent, versus 94 percent, for the combination and placebo groups, respectively. The two-year OS rates were 91 percent and 77 percent.
The risk of distant metastases or death was reduced by 49 percent with the combination versus placebo. Additionally, there was a 53 percent improvement in freedom from recurrence with the combination.
Adverse events (AEs) were experienced by 97 percent of those treated with dabrafenib and trametinib versus 88 percent with placebo.
"There were fortunately no fatal adverse events with the combination of dabrafenib and trametinib. There were no new toxicities that were not described for stage 4 melanoma," said Hauschild.
The FDA initially granted an accelerated approval to the combination of dabrafenib and trametinib for patients with BRAF-mutant metastatic melanoma in January 2014. The combination received a full approval in November 2015, and is now also indicated for the treatment of patients with BRAF-mutant non—small cell lung cancer.