Year: 2024
Type: article
Study design: Observational Study
Abstract: BACKGROUND: The co-occurrence of PD-L1 positivity and EGFR mutations in advanced NSCLC often limits EGFR-TKIs effectiveness, with unclear mechanisms. METHODS: We analyzed 103 treatment-naive EGFR-mutant LUAD patients from three centers, assessing PD-L1 expression and performing NGS analysis. RESULTS: = 0.023). The DNA Damage Response and Repair (DDR) pathogenic deficiency mutations, along with biological processes and signaling pathways related to DNA recombination, cell cycle transition and abnormal phosphorylation, were more prevalent in the PD-L1 ≥ 1% group. PIK3CA and RARA clonal alterations were more common in PD-L1 < 1% group, while TP53 clonal mutations predominated in PD-L1 ≥ 1% group. Retrospective analysis showed EGFR-TKIs plus chemotherapy extended median PFS by 9.8 months, potentially overcoming EGFR-TKI monotherapy resistance. CONCLUSION: This study elucidates the genomic characteristics of PD-L1-induced resistance to EGFR-TKIs. For patients with concurrent mutations in EGFR and PD-L1 expression, a first-line treatment strategy combining EGFR-TKIs with chemotherapy may offer a more effective alternative.
Source: Future Oncology
Authors: Guangming Yi, Fanghao Cai, Liangzhong Liu, Rongxin Liao, Xuan Jiang, Zhenzhou Yang, Xiaoyue Zhang
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Award: G504305494
OpenAlex ID: W4405507542