Intermittent BRAF Inhibition Can Achieve Prolonged Disease Control in BRAF Mutant Melanoma

BRAF V600E is the most common somatic mutation seen in patients with metastatic melanoma. BRAF inhibitors (BRAFi), along with MEK inhibitors (MEKi), have been shown to improve overall survival in these patients with a median time to resistance of 6-10 months. We describe a patient with an ongoing response of 48 months on intermittent BRAFi therapy. She was started on vemurafenib at initial diagnosis, which was discontinued after a total of 39 weeks of therapy, and achieved a complete response due to cumulative toxicity. Upon evidence of progression on serial imaging following 81 weeks of disease-free status, BRAFi was resumed with dabrafenib, along with trametinib. Complete response was seen with seven weeks of treatment. Therapy was discontinued again, due to side effects, with an intention to pursue intermittent therapy. Serial imaging, so far, has shown no progression or recurrence of disease after over a year (66 weeks and ongoing) since discontinuation of therapy. This case underscores the clinical feasibility of intermittent BRAFi therapy in patients while still achieving a prolonged response. Disease control of 48 months, to date, has been achieved using therapy only "as needed" and keeping toxicities to the minimum.