Enhancing First-Line TKI Efficacy in PD-L1-Positive EGFR-Mutated NSCLC: The Role of Antiangiogenic Agents

Abstract

Background: 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. Methods: In our retrospective study, we examined data from 201 NSCLC patients with advanced EGFR mutations, treated at two centers of Shaw Hospital in Zhejiang, China. This analysis covered a period from January 1, 2013, to April 30, 2023. Results: Patients with PD-L1 positivity exhibited a markedly shorter average PFS (9.2 months compared to 18.0 months, P<0.001) and OS (43.3 months versus 69.1 months, P=0.0011) relative to those without PD-L1 expression. This difference in both PFS and OS remained statistically significant even after adjusting for multiple factors (P<0.001 for PFS and P=0.002 for OS). In the PD-L1-positive cohort, introducing antiangiogenic therapy in the first line of treatment significantly extended both PFS (increasing from 8.6 to 25.7 months, P=0.03) and OS (from 29.7 to 53.5 months, P=0.026). Post-first-line TKI therapy, 39.3% of PD-L1-positive patients and 56.1% of PD-L1-negative patients developed the T790M mutation (P=0.157), with no notable difference in PFS from second-line TKI treatments between the groups (9.3 vs. 14.7 months, P=0.16). Additionally, subsequent immunotherapy markedly prolonged OS in the PD-L1-positive group (from 42 to 68.4 months, P=0.046). However, for PD-L1-negative patients, neither antiangiogenic therapy nor later-line immunotherapy demonstrated significant benefits in PFS or OS. Conclusion: Individuals exhibiting positive PD-L1 status generally experience reduced PFS and OS. Implementing antiangiogenic treatments or subsequent combined immunotherapy has shown effectiveness in enhancing outcomes for these patients.