In recent years, combined BRAF/MEK inhibition has become the undisputed standard of care for patients with BRAFV600-mutated locally advanced or metastatic melanoma.1–3 The basis for this was formed by the results of several, large randomised trials demonstrating a superior overall survival with dual BRAF/MEK inhibition compared to BRAF inhibitor monotherapy, which was accompanied by a manageable tolerability. 1–3 In the randomised phase III COLUMBUS trial the combination of the BRAF inhibitor encorafenib with the MEK inhibitor binimetinib (COMBO450) was compared to monotherapy with either vemurafenib or encorafenib in patients with BRAFV600-mutated advanced melanoma. Previous reports of this trial already demonstrated that the COMBO450 regimen significantly prolonged both the extend the median progression-free (PFS) and overall survival (OS) compared to vemurafenib alone. During ASCO 2020, a 4-year landmark analysis with additional follow-up of this trial was presented. These updated results confirm the earlier findings and indicate that COMBO450 is associated with a long-term benefit in patients with BRAFV600-mutated melanoma.