A retrospective analysis of 97 NSCLC patients with kinase domain-retaining BRAF fusions, stratified into de novo (n=43) and acquired (n=54) groups, examining molecular characteristics, co-occurring genomic alterations, and treatment outcomes.
104 BRAF fusions across 53 unique partner genes (29 novel) were identified; 65.1% of de novo cases lacked co-occurring drivers; acquired BRAF fusions arose predominantly after EGFR-TKI therapy (63.0% of acquired cases); one patient with TRIM24-BRAF + EGFR exon 19 deletion benefited from dual MEK + EGFR inhibition.
Retrospective design limits causal inference; no prospective outcome data for BRAF fusion-directed therapies; single case illustrating MEK + EGFR inhibition benefit makes efficacy conclusions premature.
Repeat comprehensive genomic profiling at disease progression in EGFR-mutant NSCLC to detect acquired BRAF fusions as a resistance mechanism. For patients with co-occurring BRAF fusions and EGFR mutations, dual MEK plus EGFR inhibition is a rational combination to consider.
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