Objectives:(1) Review the significant advancements in targeted therapeutic approaches available for patients with metastatic BRAF-mutant melanoma. (2) Describe our favorable early experience treating marginally resectable regionally advanced BRAF-mutant melanoma with neoadjuvant BRAF/MEK co-inhibition in order to avoid a cosmetically and functionally disabling resection. 

Methods: Retrospective chart review of two patients presenting with large marginally resectable regionally advanced BRAF-mutated metastatic melanoma.  Mutation status was confirmed in both patients via the Cobas 4800 BRAF V600 Mutation Test (Real-Time PCR).  Both patients were evaluated by a multidisciplinary team of physicians including otolaryngology, dermatology, medical oncology, pathology, and radiology.

Results: Both patients achieved maximal response to neoadjuvant BRAF/MEK co-inhibitor therapy after 6 months of therapy, with significant reduction in tumor burden. The first patient’s neck metastasis reduced in size from 13 cm to 4 cm, and the second patient’s reduced in size from 9 cm to being undetectable on exam and imaging. They then underwent planned selective neck dissections without any intraoperative complications. Surgical pathology specimens from the second patient demonstrated no residual metastatic disease in all 33 lymph nodes excised, while the first patient did have evidence of residual disease, with all surgical margins being negative. The patients required no further treatment, are 16 and 13 months from surgery, respectively, and remain in remission both clinically and radiographically. 

Conclusion: The use of neoadjuvant BRAF/MEK co-inhibition may represent a novel therapeutic paradigm providing a more oncologically, functionally, and cosmetically favorable outcome for patients with bulky marginally resectable regional neck disease that would traditionally require a radical morbid surgical resection. While this novel therapeutic approach still required selective neck dissection of the same neck levels as a conventional radical resection, all vital neurovascular structures and neck musculature were able to be preserved.