2024 World Conference on Lung Cancer (WCLC) - Posters-P2.11A.25 Clinicogenomic Profile of Different Resistance Patterns to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer

P2.11A.25 Clinicogenomic Profile of Different Resistance Patterns to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer

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The study investigates resistance patterns to immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) patients without EGFR/ALK driver mutations. Despite ICIs providing durable responses, resistance—either primary or acquired—remains prevalent, affecting over half the patients. Utilizing the MD Anderson GEMINI database, researchers identified metastatic NSCLC patients treated with ICI alone or in combination with chemotherapy. Mutational profiling via targeted next-generation sequencing (NGS) was conducted, and the radiographic response was assessed using RECIST guidelines.<br /><br />Key findings highlight genetic alterations associated with resistance. Genes related to PI3K/AKT/mTOR (such as PIK3CA), RAF/MEK/ERK pathways (including ARAF, BRAF), as well as ErbB family genes (EGFR, ERBB2, MET), showed higher presence post-ICI treatment compared to pre-treatment. Patients with acquired resistance (AR) exhibiting partial or complete response initially, but later showing disease progression, were found to have squamous histology, liver metastasis, and were often treated with combination therapy. A significant factor observed was an elevated peripheral blood derived neutrophil-to-lymphocyte ratio (dNLR), associated with earlier disease progression.<br /><br />Among 37 patients, a notable decrease in PD-L1 expression post-treatment was observed compared to baseline levels at disease progression. Patients with liver metastases and higher dNLR were found to have quicker onset of acquired resistance. The study emphasizes the genomic heterogeneity at the point of resistance, underlining the need to understand the mechanisms of resistance evolution better. Such insights could potentially optimize sequential or combinatorial treatment strategies to overcome resistance in NSCLC patients. The research contributes critical data for developing targeted approaches to manage resistance in this patient group.

Asset Subtitle

Lingzhi Hong

Meta Tag

Speaker Lingzhi Hong

Topic Metastatic NSCLC – Immunotherapy

Keywords

immune checkpoint inhibitors

non-small cell lung cancer

resistance patterns

EGFR/ALK mutations

metastatic NSCLC

next-generation sequencing

PI3K/AKT/mTOR pathway

genomic heterogeneity

acquired resistance

PD-L1 expression