The findings, in the New England Journal of Medicine, apply to patients whose tumors had BRAF V600E or V600K mutations. The drug combination was given for 12 months.
The results "suggest that treatment with dabrafenib plus trametinib does not merely delay relapse but increases the percentage of patients who are likely to remain relapse-free in the long term," Dr. Reinhard Dummer of University Hospital Zurich Skin Cancer Center, in Switzerland, and colleagues write.
A 2017 analysis had estimated that the three-year relapse-free survival rate was 58% with the drug combination and 39% among volunteers who received placebo tablets (P<0.001).
Now, after a minimum follow-up of 59 months, the five-year relapse-free survival rate has been found to be 52% with the drug combination versus 36% with placebo (hazard ratio, 0.51; 95% confidence interval, 0.42 to 0.61).
The treatment caused serious side effects in 36% of patients, compared with 10% in the placebo group, and cost about $245,000 for the year. GlaxoSmithKline and Novartis paid for the study.
The team has been following 870 participants in 25 countries who were randomly assigned to receive either placebo or 150 mg of oral dabrafenib (Tafinlar) twice daily and 2 mg of oral trametinib (Mekinist) once a day after recovering from their surgery. None had received previous systemic anticancer treatment or radiotherapy.
At the five-year mark, 65% receiving the combination were alive without distant metastasis compared with 54% in the placebo group.
In the three-year analysis, the COMBI-AD team reported the survival rate for the 435 taking the two drugs was 86% versus 77% for the 432 in the placebo group (P=0.0006).
Among the deaths, melanoma was responsible for 90% in the treatment group and 83% among placebo patients.
In the new report, they say that "overall survival was not analyzed, since the required number of events to trigger the final overall survival analysis had not been reached."
Forty percent of patients receiving the combination therapy and 54% of placebo recipients needed subsequent therapy.
Side effects rated grade 3 or 4 appeared in 36% of the combination therapy group versus 10% with placebo. They included hypertension (found in 6% of drug patients), pyrexia (5%), fatigue (4%) and elevated levels of alanine aminotransferase and aspartate aminotransferase (4% each).
The vast majority of side effects were only seen during the 12-month treatment window and "nearly all" associated with the drug combination "were transient and resolved after the discontinuation or interruption of treatment," the researchers said.
The trial was sponsored by GlaxoSmithKline until Novartis took control of the two drugs on March 2, 2015. It was not large enough to determine whether the type of BRAF mutation made a difference in the outcome; 91% of the patients had the BRAF V600E mutation.
By Reuters Staff
SOURCE: https://bit.ly/32Gk40F and https://bit.ly/2wUDHDu The New England Journal of Medicine, online September 2, 2020.
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