Treating Stage IV BRAF-Mutated Melanoma
An expert perspective on how to best treat a patient diagnosed with stage IV BRAF-mutated 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 Perspective, featuring Michael B. Atkins, MD.
Based on the DREAMseq trial (NCT02224781) results, first-line nivolumab plus ipilimumab is the optimal approach for this typical patient with BRAF-mutant metastatic melanoma and M1b disease. This combination demonstrated superior 2-year progression-free and overall survival over first-line targeted therapy across clinical subsets, including in those with M1b disease. There are no apparent comorbidities or frailty that should preclude tolerating immunotherapy for this patient.
Biomarker analyses show most tissue-based biomarkers, such as interferon-g signature and PD-L1 expression, favor initial immunotherapy as well. However, a proangiogenesis tumor signature was associated with improved outcomes from first-line targeted therapy followed by second-line immunotherapy. The targeted therapy may shrink tumors, improving oxygenation and immune sensitivity when immunotherapy is given subsequently.
The SECOMBIT trial (NCT02631447) evaluated a “sandwich” approach with initial brief targeted therapy followed by nivolumab plus ipilimumab, then resuming targeted therapy at progression. This approach led to improved outcomes over immunotherapy alone for patients with highly elevated lactate dehydrogenase levels, suggesting aggressive, rapidly proliferating tumors.
Although biomarker-directed sequences may eventually refine treatment, combination immunotherapy remains the clear first-line choice for this patient with typical BRAF-mutant M1b melanoma.
Video synopsis is AI-generated and reviewed by Targeted Oncology® editorial staff.
