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 <i>EGFR</i>-mutated NSCLC, the development of resistance is nearly inevitable. <i>BRAF</i> mutations and fusions are reported in 1% to 3% of patients with <i>EGFR</i>-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 <i>EGFR</i>-mutated NSCLC treated with osimertinib that developed a <i>CTNNA</i> <i>1-BRAF</i> fusion at progression. In addition, we provide a brief overview of the current evidence of <i>BRAF</i> fusions as an acquired resistance mechanism to osimertinib and potential treatment strategies.