Treatment discontinuation after complete response to BRAF/MEK inhibition in metastatic melanoma: long-term clinical outcomes from a single institution

Abstract

The optimal duration of BRAF/MEK inhibitor therapy in patients with metastatic melanoma who achieve complete response remains uncertain. Although targeted therapy is commonly continued until disease progression or unacceptable toxicity, prolonged treatment may be associated with chronic adverse events, impaired quality of life, and treatment fatigue. We performed a retrospective single-center analysis of patients with BRAF -mutated metastatic melanoma who achieved radiologically confirmed complete response during combined BRAF/MEK inhibition and subsequently discontinued therapy. Clinical characteristics, treatment duration, reasons for discontinuation, recurrence, and postdiscontinuation outcomes were evaluated. Ten patients fulfilled the inclusion criteria; the median age was 59.5 years (range, 36–85 years), and six were male. The median treatment duration was 36.1 months, and the median time to complete response was 9.8 months. Discontinuation occurred because of patient preference in six patients, treatment-related toxicity in three, and temporary drug unavailability in one. At last follow-up, eight patients remained in sustained complete remission and two developed recurrence. Both recurrences occurred within the first months after treatment cessation. One patient developed isolated brain metastases approximately 3 months after discontinuation, while another experienced locoregional recurrence. The longest treatment-free remission approached 10 years. In this single-institution real-world series, discontinuation of BRAF/MEK inhibition after complete response was associated with durable remission in most patients. Treatment discontinuation may be feasible in carefully selected patients with sustained complete response, provided that close clinical and radiological surveillance is maintained.