dabrafenib + osimertinib + trametinib

This is a combination therapy consisting of three small molecule inhibitors—dabrafenib, osimertinib, and trametinib—used in the treatment of non-small cell lung cancer (NSCLC) with acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) due to the emergence of a BRAF V600E mutation. Dabrafenib is a BRAF inhibitor targeting mutant BRAF V600E; trametinib is a MEK1/2 inhibitor that blocks downstream signaling in the MAPK pathway; and osimertinib is an EGFR tyrosine kinase inhibitor effective against both sensitizing EGFR mutations and T790M resistance mutations. The triple combination aims to overcome acquired resistance mechanisms by simultaneously inhibiting EGFR, BRAF, and MEK pathways. Clinical case series and retrospective studies have shown promising efficacy—including partial responses and disease control—in patients who developed BRAF V600E-mediated resistance after prior osimertinib therapy for EGFR-mutant NSCLC. Adverse events are common but generally manageable with dose adjustments[1][2][3][4][6][9].