2022 World Conference on Lung Cancer (ePosters)-EP08.02-044. Adding Alectinib Rescues Progression on Osimertinib Due to Acquired ALK p.R1275Q Variant in EGFR p.L858R-mutated NSCLC

EP08.02-044. Adding Alectinib Rescues Progression on Osimertinib Due to Acquired ALK p.R1275Q Variant in EGFR p.L858R-mutated NSCLC

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This case report discusses the use of a liquid biopsy-guided approach in the treatment of a 80-year-old woman with advanced non-small cell lung cancer (NSCLC). The patient had EGFR p.L858R and TP53 p.C277F mutations and had previously been treated with osimertinib, but experienced progression and toxicity, and a re-challenge with osimertinib was ineffective. The patient's plasma cfDNA showed the emergence of an acquired ALK p.R1275Q mutation.<br /><br />To address the resistance to osimertinib, the patient was treated with a combination of osimertinib and alectinib. This is the first reported case of a durable response to this combination therapy in the presence of an acquired ALK mutation, suggesting that ALK p.R1275Q may be a mechanism of osimertinib resistance that can be effectively countered by alectinib.<br /><br />The authors highlight the importance of a liquid biopsy-guided approach for progression in elderly patients with reduced performance status (PS). In this case, the use of liquid biopsy to detect the acquired ALK mutation allowed for a targeted approach to treatment with osimertinib and alectinib.<br /><br />The report concludes that combining ALK and EGFR tyrosine kinase inhibitors (TKIs) may be a feasible and effective therapy for patients with acquired ALK mutations. This case demonstrates the potential for personalized medicine approaches in the treatment of NSCLC, particularly in cases of acquired resistance to targeted therapies. The findings also suggest that further research is needed to explore the mechanisms of resistance to osimertinib and potential strategies for overcoming this resistance.

Asset Subtitle

Edyta Maria Urbanska

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Speaker Edyta Maria Urbanska

Topic Metastatic Non-small Cell Lung Cancer - Molecular Targeted Treatments

Keywords

liquid biopsy-guided approach

non-small cell lung cancer

NSCLC

EGFR p.L858R mutation

TP53 p.C277F mutation

osimertinib

ALK p.R1275Q mutation

alectinib

elderly patients

acquired resistance to targeted therapies