Treatment Options for Metastatic Melanoma

Case: A 62-Year-Old Female with Stage IV Melanoma

• A 62-year-old female consulted with her dermatologist for removal of a pigmented lesion that had recently become darker.
  • She noted that she had been experiencing persistent fatigue, shortness of breath, and a dry cough that she attributed to a prior COVID-19 infection.
  • LDH: 174 UI/L
• Excisional biopsy reveals melanoma with a Breslow depth of 1.2 mm, ulcerated, mitotic rate 4/mm2
  • The patient underwent wide local excision and sentinel node mapping
  • Staining was positive for melanoma in the right axillary node
  • CT of the chest, abdomen, and pelvis indicated multiple lesions in both lungs
  • The patient underwent core-needle biopsy of the largest lung lesion, measuring 1 cm
  • Pathology revealed metastatic melanoma, cutaneous nonacral with a positive BRAF V600E mutation
  • ECOG PS 1
• Diagnosis: Stage IV Melanoma, T2b N1a M1b

This is a video synopsis/summary of a Case-Based Peer Perspectives episodefeaturing Michael B. Atkins, MD.

There are several first-line systemic therapy options for patients with BRAF-mutated metastatic melanoma. Three combinations of BRAF inhibitors (dabrafenib, encorafenib,vemurafenib) and MEK inhibitors (trametinib, binimetinib, cobimetinib) are FDA approved. They have superior response rates, progression-free survival (PFS), and overall survival compared with BRAF inhibitor monotherapy in phase 3 trials. The HRs for PFS benefit are similar, approximately 0.54-0.58. Choice of regimen is usually based on toxicities and administration needs.

Immunotherapy options include pembrolizumab or nivolumab monotherapy, with approximately 40% response rates; nivolumab plus ipilimumab, which showed a 14% PFS/overall survival (OS) benefit at 5 to 6.5 years over nivolumab alone for BRAF-mutant melanoma in the CheckMate 067 trial, suggesting this combination is preferred for eligible patients; and relatlimab plus nivolumab, which was recently approved based on the RELATIVITY-047 trial showing PFS/OS benefit over nivolumab alone in BRAF-mutant and wild-type melanoma.

With many options, key considerations are efficacy, toxicity, and administration needs.

Video synopsis is AI-generated and reviewed by Targeted Oncology® editorial staff.