Combined Therapy with Anti-PD1 and BRAF and/or MEK Inhibitor for Advanced Melanoma: A Multicenter Cohort Study

Area of Science:

• Oncology
• Dermatology
• Clinical Research

Background:

• Advanced melanoma requires novel therapeutic strategies, especially for patients resistant to immune checkpoint inhibitors (ICI) or targeted therapies (TT).
• BRAF-mutated melanomas present challenges with resistance to existing treatments, necessitating effective salvage options.

Purpose of the Study:

• To evaluate the safety and efficacy of combined ICI and TT as a rescue therapy in advanced melanoma patients.
• To assess real-world clinical practice outcomes for melanoma patients receiving combined anti-PD1 and BRAF inhibitor (BRAFi) and/or MEK inhibitor (MEKi) therapy.

Main Methods:

• A prospective, multicentric study (MelBase cohort) included 59 advanced melanoma patients treated with combined anti-PD1 and BRAFi and/or MEKi.
• Patients received triple combination, anti-PD1 + BRAFi, or anti-PD1 + MEKi therapies.
• Safety was assessed by monitoring Grade 3-4 adverse events and treatment discontinuation/dose reduction due to toxicity.

Main Results:

• Grade 3-4 adverse events occurred in 12% of patients; 14% required permanent discontinuation and 7% dose reduction for toxicity.
• In BRAF wild-type patients, anti-PD1 + MEKi showed an 83% tumor control rate and 7.1 months median progression-free survival.
• The combination therapies were generally well-tolerated as a rescue line for advanced melanoma.

Conclusions:

• Combined ICI and TT strategies represent a safe and effective rescue option for advanced melanoma patients with prior treatment resistance.
• Anti-PD1 and MEK inhibitor combination demonstrates significant efficacy in BRAF wild-type melanoma, warranting further prospective investigation.
• Real-world data supports the use of these combinations in clinical practice for refractory melanoma cases.