Long-Term Follow-up Shows Continued Benefit With Dabrafenib Plus Trametinib in Stage III Melanoma
Posted: Thursday, January 3, 2019
Published in the Journal of Clinical Oncology, extended follow-up has confirmed the initial results of the COMBI-AD study: adjuvant dabrafenib plus trametinib improved relapse-free survival versus placebo in patients with resected BRAF V600–mutant stage III melanoma. In fact, according to Axel Hauschild, MD, PhD, of the University Hospital Schleswig-Holstein, Germany, and international colleagues, “subgroup analysis suggested that dabrafenib plus trametinib benefited patients regardless of baseline factors.”
In the randomized, double-blind study, 870 participants were assigned to receive either 12 months of dabrafenib at 150 mg twice daily plus trametinib at 2 mg once daily (n = 438) or placebo (n = 432). Although the primary analysis of study results spanned a median follow-up of approximately 34 months, the secondary analysis included a median follow-up of 44 months in the dabrafenib plus trametinib group and 42 months in the placebo group.
A secondary analysis found that the estimated relapse-free survival rate was 59% for the dabrafenib plus trametinib versus 40% for the placebo group at 3 years and 54% versus 38% at 4 years (hazard ratio = 0.49). A similar relapse-free survival benefit of dabrafenib plus trametinib was found across various subgroups, including disease stage, nodal metastatic burden, and tumor ulceration. The combination therapy arm was associated with an estimated cure rate of 54% versus 37% in the placebo arm.
“Although comparisons between clinical trials should be interpreted cautiously,” the study authors commented, “2-year [relapse-free survival] rates in patients with stage IIIB/C disease (per [American Joint Committee on Cancer] 7th edition) were similar in the nivolumab arm of the CheckMate-238 trial (64%) and in the dabrafenib plus trametinib arm of the COMBI-AD trial (63%).”
Disclosure: Study authors’ disclosure information may be found at the JCO.