2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.12A.31 Clinical Characteristics and Outcomes of EGFR-Positive Non-Small Cell Lung Cancer with Acquired RET Fusions

EP.12A.31 Clinical Characteristics and Outcomes of EGFR-Positive Non-Small Cell Lung Cancer with Acquired RET Fusions

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The study examines the clinical characteristics and outcomes of patients with EGFR-positive non-small cell lung cancer (NSCLC) who develop resistance via RET fusions after treatment with osimertinib. Osimertinib is the standard treatment for EGFR mutation-positive NSCLC, but resistance can develop, sometimes through acquired RET fusions. The study focuses on the limited exploration of these characteristics and the effectiveness of a combined therapy of osimertinib and selpercatinib.<br /><br />In this retrospective analysis, researchers reviewed cases at the National Cancer Center Hospital in Japan where patients underwent next-generation sequencing (NGS) testing after osimertinib failure to identify the occurrence of RET fusions. Out of 45 patients reviewed, 3 (7%) were found to have acquired RET fusions. These were all women with adenocarcinoma, and their EGFR mutations varied.<br /><br />The clinical outcome varied among the cases: two showed stability or partial response with selpercatinib after osimertinib, while the third showed progression. Adverse events from the treatment were generally consistent with known individual drug profiles, with no grade 3 or higher adverse events reported during the study.<br /><br />The study's results align with previous research showing a small percentage of patients develop RET fusions after acquiring resistance to osimertinib, particularly those with EGFR exon 19 deletions. The presence of diverse RET fusion partners indicates tumor heterogeneity.<br /><br />Overall, the combination therapy was deemed feasible and showed some effectiveness, but responses were mixed, highlighting the complexity of resistance mechanisms. The study concludes that while the combination treatment has potential, further investigation into the heterogeneity of resistance mechanisms is necessary to optimize therapeutic strategies for EGFR-positive NSCLC patients with acquired RET fusions.

Asset Subtitle

Takayuki Kobayashi

Meta Tag

Speaker Takayuki Kobayashi

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

EGFR-positive

non-small cell lung cancer

osimertinib resistance

RET fusions

selpercatinib

next-generation sequencing

adenocarcinoma

tumor heterogeneity

combination therapy

therapeutic strategies