| 要約: | Background: BRAF V600 mutations are the epitome of targeted therapy. However, not much is known about non-V600 mutations. Using the new data infrastructure of the Swiss Personalized Oncology project of the Swiss Personalized Health Network (SPHN), we evaluated the fate of patients with cancer with non-V600 BRAF mutations in comparison to patients with class 1 mutations. Patients and methods: In this retrospective observational multicenter study, we have assembled a cohort of 392 patients with class 1 and 154 patients with nonclass 1 BRAF mutations (76 colorectal cancers, 96 lung cancers, 297 melanomas, and 77 other cancers). We carried out outcome analyses between mutational classes and therapeutic subgroups. Results: Overall survival (OS) did not differ significantly between patients with class 1 and nonclass 1 mutations. Upon treatment with BRAF/MEK inhibitors, patients with class 1 mutant melanoma showed numerically longer progression-free survival (PFS; 217 days) than patients with nonclass 1 mutant disease (73 days). Overall, in patients with class 2 or 3 mutations, BRAF and MEK inhibitors showed no benefit over other systemic therapies. However, specific class 2 mutations such as K601E may confer sensitivity to BRAF/MEK inhibitors, with two out of five patients achieving a PFS >400 days. Conclusions: The diversity of BRAF mutations presents significant treatment challenges. Despite similar OS, nonclass 1 mutant tumors showed a trend toward lower PFS with BRAF/MEK blockade. Selected class 2 mutations may confer sensitivity to BRAF/MEK inhibitors. This highlights the rationale for a mutation, rather than class-specific, clinical approach against nonclass 1 BRAF-mutant tumors.
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