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Background <p>Non-small cell lung cancer (NSCLC) with <i>EGFR</i> mutations often develops resistance to tyrosine kinase inhibitors (TKIs), with acquired <i>BRAF</i> V600E mutation being a rare but clinically challenging mechanism. The efficacy of combined <i>EGFR</i> and <i>BRAF/MEK</i> inhibition in this setting is not sufficiently characterized.</p> Case presentation <p>A 56-year-old never-smoker with stage IVA <i>EGFR</i> exon 19del-mutant lung adenocarcinoma developed progressive disease on osimertinib, with a new <i>BRAF</i> V600E mutation detected via next-generation sequencing (NGS). She was treated with osimertinib (80&#xa0;mg daily), dabrafenib (150&#xa0;mg twice daily), and trametinib (2&#xa0;mg daily), achieving:&#xa0;Radiological response: Regression of metastatic lesions (left lower lobe residual nodule) and stable disease in the primary lesion.&#xa0;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.&#xa0;Durable control: Progression-free survival (PFS) of 11 months (last follow-up: May 2025).</p> Conclusion <p>Triple therapy with osimertinib, dabrafenib, and trametinib represents a viable and well-tolerated approach for <i>EGFR</i>-mutant NSCLC with acquired <i>BRAF</i>V600E resistance. Molecular profiling upon progression is essential to guide targeted therapy.</p>

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

  • 期刊论文

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  • 发表日期：

    2025年10月10日

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  • MingHui Lin,
  • XuYu Chen,
  • Fan Lin,
  • YanBo Yang

摘要

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.