Targeted BRAF /MEK inhibition as a salvage therapy for patients with metastatic melanoma harboring a BRAF L597R mutation: two case reports and review of the literature.
Andrew Moufarrej, Sarah Biermann, Robin Springer et al.
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Case in brief
Two patients with metastatic melanoma harboring the BRAF L597R mutation had rapid clinical deterioration and disease progression after dual immune checkpoint inhibition. Switching to targeted therapy—binimetinib in one case and binimetinib plus encorafenib in the other—was followed by rapid tumor-burden reduction and symptomatic improvement. Resistance led to progression after 3 months in the first patient. In the second, targeted therapy was stopped after 8 weeks because of anticipated resistance, and immune checkpoint inhibition was restarted; stable disease and symptom control continued for an additional 6 months before progression. Overall survival was 10 and 11 months, respectively.
What made this case unusual
Both patients with the rare class II BRAF L597R mutation showed rapid clinical responses to BRAF/MEK-targeted therapy despite progression on dual immune checkpoint inhibition; the responses were followed by early resistance or concern for its emergence.
Diagnostic / clinical pearl
In metastatic melanoma with BRAF L597R, BRAF/MEK inhibition may produce rapid tumor and symptom improvement, but the reported responses were limited by early resistance.
Why it matters
These cases provide clinical observations on targeted therapy in a rare BRAF-mutated melanoma subtype for which efficacy remains unclear.