2023 World Conference on Lung Cancer (Posters)-EP12.01. Metastatic NSCLC with G719X/S781I EGFR-mutations with acquired BRAF V600E mutation - response to Osimertinib, Dabrafenib and Trametinib

EP12.01. Metastatic NSCLC with G719X/S781I EGFR-mutations with acquired BRAF V600E mutation - response to Osimertinib, Dabrafenib and Trametinib - PDF(Abstract)

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This case report discusses a 73-year-old woman diagnosed with metastatic non-small cell lung cancer (NSCLC) harboring rare EGFR mutations. The patient initially responded well to treatment with Erlotinib, but later developed severe skin toxicity and was switched to Osimertinib. However, the cancer progressed and a new tumor emerged, leading to a rebiopsy of the patient's lung tissue.<br /><br />The rebiopsy identified a new and druggable mutation in the BRAF gene (p.V600E), which was not present in the original diagnostic biopsy. This acquired BRAF mutation indicated a potential resistance mechanism to EGFR-targeted therapies. Further analysis using targeted next-generation sequencing (NGS) and gene fusions revealed that the patient had wild-type EGFR and no BRAF mutations in the circulating tumor DNA.<br /><br />The patient received 3rd line treatment with a combination of BRAF and MEK inhibitors (Dabrafenib and Trametinib), which resulted in a partial response in the sampled pulmonary lesion but progression in other tumors. To target both the acquired BRAF mutation and the remaining EGFR mutations, triple therapy with BRAF/MEK inhibitors and Osimertinib was implemented, leading to stable disease.<br /><br />This case highlights the importance of rebiopsies in EGFR-mutated NSCLC patients who have acquired resistance to EGFR-targeted therapies. It shows that acquired mutations, such as BRAF p.V600E, can become druggable targets and provide opportunities for further treatment. Additionally, the study emphasizes the heterogeneity of NSCLC and the need for combination therapies to effectively target multiple mutations in order to achieve better treatment outcomes. This is the first reported case of an acquired BRAF p.V600E mutation in a NSCLC patient with uncommon EGFR mutations successfully treated with triple therapy targeting both BRAF and EGFR.

Asset Subtitle

Edyta Urbanska

Meta Tag

Speaker Edyta Urbanska

Topic Metastatic NSCLC: Targeted Therapy - EGFR/HER2

Keywords

metastatic non-small cell lung cancer

EGFR mutations

Erlotinib

Osimertinib

BRAF gene

resistance mechanism

targeted next-generation sequencing

BRAF and MEK inhibitors

triple therapy

rebiopsies