Successful treatment of osimertinib-resistant EGFR-mutant NSCLC with acquired BRAF V600E mutation using triple combination therapy: a case report with pathological confirmation.

Background: Non-small cell lung cancer (NSCLC) with EGFR mutations often develops resistance to tyrosine kinase inhibitors (TKIs), with acquired BRAF V600E mutation being a rare but clinically challenging mechanism. The efficacy of combined EGFR and BRAF/MEK inhibition in this setting is not sufficiently characterized.

Case presentation: A 56-year-old never-smoker with stage IVA EGFR exon 19del-mutant lung adenocarcinoma developed progressive disease on osimertinib, with a new BRAF V600E mutation detected via next-generation sequencing (NGS). She was treated with osimertinib (80 mg daily), dabrafenib (150 mg twice daily), and trametinib (2 mg daily), achieving: Radiological response: Regression of metastatic lesions (left lower lobe residual nodule) and stable disease in the primary lesion. Pathological confirmation: Post-surgical resection revealed only 1% residual tumor viability, indicating a major pathological response.

Tolerability: Only grade 1 rash (CTCAE v5.0) was observed. Durable control: Progression-free survival (PFS) of 11 months (last follow-up: May 2025).

Conclusion: Triple therapy with osimertinib, dabrafenib, and trametinib represents a viable and well-tolerated approach for EGFR-mutant NSCLC with acquired BRAFV600E resistance. Molecular profiling upon progression is essential to guide targeted therapy.