Adjuvant dabrafenib plus trametinib prolongs RFS in stage III melanoma

Adjuvant treatment with dabrafenib plus trametinib prolongs relapse-free survival (RFS) in patients with resected stage III BRAF V600-mutant melanoma, according to a 5-year analysis of the COMBI-AD* study presented at the ASCO20 Virtual Scientific Program.

This phase III, double-blind trial involved 870 patients aged <65 years with completely resected stage III BRAF V600-mutant melanoma. After surgery, patients were randomized in a 1:1 ratio to receive either dabrafenib 150 mg twice daily plus trametinib 2 mg once daily (n=438) or two matching placebos (n=432) for a 12-month treatment period. [ASCO20, abstract 10001]

At 5 years, more patients treated with dabrafenib plus trametinib were relapse free than those treated with placebo (52.0 percent vs 36.0 percent; hazard ratio [HR], 0.51). The median RFS was not reached in the dabrafenib plus trametinib arm and was 16.6 months in the placebo arm.

In a subgroup analysis of patients stratified by disease stage based on AJCC 7** classification, the 5-year RFS benefit with dabrafenib plus trametinib was consistent across stages IIIA (65.0 percent vs 58.0 percent; HR, 0.61), IIIB (55.0 percent vs 34.0 percent; HR, 0.50), and IIIC (45.0 percent vs 29.0 percent; HR, 0.48) compared with placebo.

“RFS curves for both treatment arms appear to be reaching a plateau, which is a good sign if we are talking about cure,” said study author Professor Axel Hauschild from the Department of Dermatology at the University of Kiel in Kiel, Germany.

Hauschild highlighted that the median distant metastasis-free survival (DMFS) was not reached in either treatment arm, but a higher DMFS rate was still observed in the dabrafenib plus trametinib than the placebo arm (65.0 percent vs 54.0 percent; HR, 0.55).

“This analysis represents the longest follow-up to date from a phase III study of a current standard of care adjuvant therapy, as it is approved and used in many countries, for patients with resected stage III BRAF V600-mutant melanoma,” said Hauschild.

“Dabrafenib plus trametinib led to long-term RFS [of] >50 percent [at 5 years] … These results suggest that 12 months of adjuvant dabrafenib and trametinib confers a long-term survival benefit in patients with stage III [BRAF V600-mutant] melanoma,” he said.

As all patients had completed the study treatment, there was no update to safety data in the current analysis. “The final overall survival analysis is event-driven and will be reported in the future,” he concluded.

*COMBI-AD: Dabrafenib with trametinib in the adjuvant treatment of high-risk BRAF V600 mutation-positive melanoma