The Evolving Treatment Paradigm in Melanoma: Targeted Therapy vs Immunotherapy

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EP: 1.The Evolving Treatment Paradigm in Melanoma: Targeted Therapy vs Immunotherapy

EP: 2.Frontline Treatment Options for Melanoma

Evolution of Melanoma Treatment Paradigms

Key Discussion Points:

• The melanoma treatment landscape has evolved dramatically over the past decade with immunotherapy emerging as a frontline approach
• Dual checkpoint blockade has demonstrated superiority over monotherapy in metastatic (but not adjuvant) setting
• DREAMseq trial established that upfront dual checkpoint blockade is superior to frontline targeted therapy (BRAF/MEK inhibition)

Key Points for Physicians:

• For BRAF-mutated melanoma, immunotherapy is generally preferred first-line over targeted therapy based on clinical trial evidence
• Consider starting with BRAF/MEK inhibitors in symptomatic patients with high LDH, rapidly progressing disease, or when rapid response is needed
• The durability of response differs significantly between immunotherapy (more durable) and targeted therapy

Notable Insights:

For patients who begin on BRAF/MEK inhibitors for disease control, the C-COMBAT study suggests a “sandwich approach” - treating with BRAF/MEK inhibition for about 8 weeks before transitioning to immunotherapy, which showed better outcomes than continuing BRAF/MEK inhibition indefinitely.

Clinical Significance:

Treatment selection for advanced melanoma has evolved to prioritize immunotherapy, with targeted therapy reserved for specific clinical scenarios requiring rapid response, with planned transition strategies to immunotherapy when possible.