AUTHOR=Jin Xuanhong , Pan Yang , Cheng Cheng , Shen Hangchen , Zhai Chongya , Yin Kailai , Zhu Xinyu , Pan Hongming , You Liangkun 

TITLE=Optimizing first-line TKI treatment efficacy in PD-L1-positive EGFR-mutated NSCLC: the impact of antiangiogenic agents

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1391972

DOI=10.3389/fphar.2024.1391972

ISSN=1663-9812

ABSTRACT=<sec><title>Background</title><p>In individuals receiving treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), those exhibiting positive PD-L1 expression might experience reduced progression-free survival (PFS). However, the effects on overall survival (OS) and the determination of efficacious treatment approaches are still not well-defined.</p></sec><sec><title>Methods</title><p>In our retrospective study, we examined data from 193 NSCLC patients with advanced <italic>EGFR</italic> mutations who received first-line TKI treatments, treated at two centers of Shaw Hospital in Zhejiang, China. This analysis covered a period from 1 January 2016 to 30 April 2023.</p></sec><sec><title>Results</title><p>Patients with PD-L1 positivity exhibited a markedly shorter average PFS (9.5 months versus 17.8 months, <italic>P</italic> &lt; 0.001) and OS (44.4 months versus 65.7 months, <italic>P</italic> = 0.016) relative to those without PD-L1 expression. This difference in both PFS and OS remained statistically significant even after adjusting for multiple factors (<italic>P</italic> &lt; 0.001 for PFS and <italic>P</italic> = 0.028 for OS). In the PD-L1-positive cohort, introducing combination antiangiogenic significantly extended both PFS (from 9.1 to 25.7 months, <italic>P</italic> = 0.026) and OS (from 42 to 53.5 months, <italic>P</italic> = 0.03). Post-first-line TKI therapy, 39.3% of PD-L1-positive patients and 54.5% of PD-L1-negative patients developed the T790M mutation (<italic>P</italic> = 0.212), with no notable difference in PFS from second-line TKI treatments between the groups. Additionally, subsequent combination therapy with immunotherapy markedly prolonged OS in the PD-L1-positive group. However, for PD-L1-negative patients, neither combination antiangiogenic therapy nor later-line immunotherapy demonstrated significant benefits in PFS or OS.</p></sec><sec><title>Conclusion</title><p>For PD-L1-positive patients, combined antiangiogenic treatments and immunotherapy can significantly improve survival outcomes. In contrast, PD-L1-negative patients show less benefit from these therapies, highlighting the greater efficacy of these treatments in PD-L1-positive individuals.</p></sec>