LAUSR

initial data from the COMBi-aD trial suggested promising benefits of adjuvant dabrafenib plus trametinib (D + t) for patients with high-risk, stage iii, BRAF-mutant melanoma. Now, extended follow-up data from the trial confirm these benefits. as Georgina Long explains, “the Kaplan–Meier curves remained separated at 4 years, with D + T significantly improving relapse-free survival (rFs; median not reached versus 16.6 months with placebo; HR 0.49, 95% CI 0.40–0.59, equating to a 51% reduction in the risk of recurrence).” Notably, the RFS benefits were similar irrespective of disease stage, nodal metastatic burden or ulceration. “using a cure rate model, we estimate that 54% of the D + t group will remain relapse-free in the long-term, compared with only 37% of the placebo group — a 17% absolute difference,” Long adds. at the esMO 2018 Congress, Long also reported biomarker data from COMBi-aD, which revealed that MAPK pathway aberrations previously associated with resistance to targeted therapy had no effect on RFS in either arm. By contrast, an IFNγ gene expression signature was highly prognostic, with an iFNγ-high status correlating with better rFs in both arms. Interestingly, a high tumour mutation burden (tMB) had added prognostic value among the iFNγ-high group of the placebo arm but not of the D + t arm. “apart from the group with iFNγ-low/TMB-high tumours that presumably have many drug resistance mechanisms and insufficient immunogenicity, all subgroups benefit from D + t, including the worst prognosis, iFNγ-low/tMB-low group.” “we might cure a large proportion of patients using adjuvant D + t, including those with the worst prognosis (IFNγ low/tMB low) who presumably have a low chance of responding to immunotherapy; however, this remains to be confirmed,” Long concludes. indeed, these findings might form a framework for patient selection in future trials of adjuvant targeted therapy and/or immunotherapy.