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(Slides)

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A 73-year-old woman diagnosed with advanced non-small cell lung cancer (NSCLC) harboring rare compound mutations in the EGFR gene (G719A and S781I) initially responded well to treatment with erlotinib. However, severe skin toxicity led to a switch to second-line treatment with osimertinib. After four months, a new lung metastasis was detected, prompting a re-biopsy to assess resistance mechanisms and identify potential new targets.<br /><br />The re-biopsy revealed the presence of an acquired BRAF V600E mutation, along with wild-type EGFR. The patient was subsequently treated with a combination of BRAF/MEK inhibitors (dabrafenib/trametinib), resulting in a partial response in the sampled pulmonary lesion but progression in other tumors. Triple therapy with BRAF/MEK inhibitors and osimertinib was then administered, leading to stable disease.<br /><br />This case highlights the importance of re-biopsies in EGFR-mutated NSCLC patients who progress on EGFR tyrosine kinase inhibitors, as they can provide valuable information about acquired resistance mechanisms and guide targeted treatment options. In this particular patient, the re-biopsy revealed the presence of an acquired BRAF V600E mutation, offering the possibility of further treatment with BRAF/MEK inhibitors.<br /><br />However, replacing osimertinib with BRAF/MEK inhibitors alone resulted in a mixed response, suggesting that some tumors may still be dependent on the original EGFR mutations. Re-challenging the patient with osimertinib in combination with dabrafenib and trametinib led to stable disease, highlighting the spatial and temporal heterogeneity of NSCLC.<br /><br />This is the first reported case of an NSCLC patient with rare EGFR mutations successfully treated with triple therapy consisting of BRAF/MEK inhibitors and EGFR tyrosine kinase inhibitor therapy. The patient's tumor journey involved multiple lines of treatment, starting with erlotinib, transitioning to osimertinib due to skin toxicity, and then incorporating dabrafenib and trametinib when the acquired BRAF mutation was detected. The ongoing response to this triple therapy has lasted for nine months.<br /><br />Overall, this case demonstrates the potential for personalized treatment approaches based on the identification of acquired resistance mechanisms in NSCLC patients, with the aim of improving outcomes and prolonging survival.

Asset Subtitle

Edyta Urbanska

Meta Tag

Speaker Edyta Urbanska

Topic Metastatic NSCLC: Targeted Therapy - EGFR/HER2

Keywords

NSCLC

EGFR gene

erlotinib

osimertinib

lung metastasis

re-biopsy

acquired BRAF V600E mutation

BRAF/MEK inhibitors

triple therapy

personalized treatment approaches