Minimal Survival Benefit for Dabrafenib, Trametinib in Melanoma

For patients with resected stage III melanoma, the use of adjuvant therapy comprising dabrafenib and trametinib shows a nonsignificant improvement in overall survival. This conclusion comes from a study published online on June 19 in the New England Journal of Medicine. The research was conducted by Dr. Georgina V. Long and her colleagues from the University of Sydney.

The study involved 870 patients who had resected stage III melanoma with BRAF V600 mutations. These patients were randomly assigned to receive either a 12-month course of dabrafenib plus trametinib or two matched placebos. The median follow-up duration for the groups was 8.33 years for the dabrafenib plus trametinib group and 6.87 years for the placebo group.

In their analysis, the researchers observed that the Kaplan-Meier estimates for overall survival favored dabrafenib plus trametinib compared to the placebo. However, this benefit was not statistically significant. The hazard ratio was 0.80 with a 95 percent confidence interval ranging from 0.62 to 1.01, and a P-value of 0.06. Despite this lack of statistical significance, the study did find consistent survival benefits across several prespecified subgroups, including among 792 patients with melanoma exhibiting a BRAF V600E mutation. Here, the hazard ratio for death was 0.75, with a 95 percent confidence interval between 0.58 and 0.96.

The study also demonstrated significant advantages for dabrafenib plus trametinib over placebo in other survival metrics. For relapse-free survival, the hazard ratio for relapse or death was 0.52, with a 95 percent confidence interval from 0.43 to 0.63. Similarly, for distant metastasis-free survival, the hazard ratio for distant metastasis or death was 0.56, with a 95 percent confidence interval between 0.44 to 0.71. The study reported no new safety concerns related to the treatment.

The authors noted that it remains unclear whether or how therapies administered after relapse might have affected the impact of adjuvant therapy on overall survival. This opens up avenues for further research to understand the interactions between subsequent treatments and initial adjuvant therapy.

The study was financially supported by GlaxoSmithKline and Novartis, with Novartis being the manufacturer of both dabrafenib and trametinib.