BRAF fusion as resistance mechanism to osimertinib in EGFR-mutated NSCLC: a case report and review of literature

Despite the efficacy of osimertinib in the first-line treatment of advanced EGFR-mutated NSCLC, the development of resistance is nearly inevitable. BRAF mutations and fusions are reported in 1% to 3% of patients with EGFR-mutated NSCLC receiving osimertinib and represent potential targetable alterations. In this case report, we discuss the rationale for EGFR-MEK co-inhibition in a patient with EGFR-mutated NSCLC treated with osimertinib that developed a CTNNA 1-BRAF fusion at progression. In addition, we provide a brief overview of the current evidence of BRAF fusions as an acquired resistance mechanism to osimertinib and potential treatment strategies.