ESMO 2023: Expert Perspectives & Insights into the Testing and Treatment of Melanoma

Expert panelists stress the importance of biomarker testing for BRAF mutations to guide treatment options when a patient is diagnosed with metastatic melanoma.

When a patient with metastatic melanoma patient tests negative for the BRAF V600E mutation, doctors recommend sending the sample for next-generation sequencing testing which can take 2-3 weeks, during which time they may start immunotherapy if the patient has aggressive disease, but ideally should wait for results to guide treatment.

The panelists emphasize the importance of obtaining tissue for BRAF-mutation testing and dedicated tissue tracking in patients with metastatic melanoma, with immunohistochemistry followed by confirmatory next-generation sequencing, and discuss the promise of liquid biopsies like ctDNA as a future biomarker tracking modality.

For patients with BRAF-mutant metastatic melanoma, doctors assess symptoms and disease status to determine if they should start treatment with combination immunotherapy, or 8-12 weeks of BRAF/MEK targeted therapy before switching to immunotherapy, which offers the possibility of durable responses or cure.

Beyond symptoms, doctors consider the psychosocial factors impacting treatment access and adherence, like insurance coverage, cost, family support, and preexisting conditions, when deciding between immunotherapy and targeted therapy for patients with BRAF-mutated metastatic melanoma.

Experts discuss a preference for ipilimumab/nivolumab as the frontline immunotherapy for patients with BRAF-mutant metastatic melanoma given its proven long-term efficacy but acknowledge nivolumab/relatlimab as an option with less toxicity, especially adrenal insufficiency.

Key opinion leaders explain that clinicians should warn patients with BRAF-mutated metastatic melanoma starting BRAF/MEK inhibitor therapy about short-term toxicities like fever, chills, and rash that can differ greatly from immunotherapy toxicities.

The panel explains which BRAF/MEK inhibitor combination therapy they each tend to turn to when treating a patient with BRAF-mutated metastatic melanoma.

The 7-year follow-up data for encorafenib/binimetinib showing that around 21% of patients remained progression-free supports BRAF/MEK inhibition as a later treatment option after immunotherapy failure, but doctors are reluctant to stop BRAF/MEK inhibitors given lack of data, even in those patients doing well long-term on the medications with minimal toxicity.

Panelists discuss the potential benefits of rechallenging patients with BRAF-mutated metastatic melanoma with BRAF/MEK inhibitors after a break from treatment, especially for those who initially responded well, and emphasizing the success of this approach in some cases, while highlighting the importance of monitoring and utilizing ctDNA tracking for more informed decision-making.

For patients with BRAF-mutated melanoma with asymptomatic brain metastases, immunotherapy, particularly the combination of ipilimumab and nivolumab, is the preferred treatment option due to its effectiveness and durability, as supported by the seven-year follow-up data from the CHECKMATE 204 trial.

Experts discuss treatment of patients with BRAF-mutated melanoma and symptomatic brain metastases, detailing radiation therapy, corticosteroid use, and the choice between BRAF/MEK inhibitor therapy and immunotherapy.

Doctors discuss the effectiveness of different treatment combinations for patients with BRAF-mutated metastatic melanoma and brain metastases, highlighting that consideration of patient preferences is essential in making treatment decisions.

The panel concludes their discussion with a call for continued research and collaboration, emphasizing the need for more understanding of targeted therapies, monitoring tools like ctDNA, and ongoing development in the field of BRAF mutant melanoma treatment.