Ivonescimab Plus Chemotherapy versus Bevacizumab Plus Chemotherapy in EGFR-Mutant Lung Adenocarcinoma After EGFR-TKI Failure: A Two-Center Retrospective Real-World Propensity Score-Matched Study

Objective: To evaluate the efficacy and safety of ivonescimab plus chemotherapy versus bevacizumab plus chemotherapy in advanced EGFR-mutant lung adenocarcinoma after EGFR-TKI failure, and provide the first real-world head-to-head comparative evidence. Methods: This two-center retrospective propensity score-matched (PSM) study enrolled 390 eligible patients, including 130 receiving ivonescimab plus chemotherapy and 260 receiving bevacizumab plus chemotherapy. A 1:1 PSM was performed to balance baseline confounders. The primary endpoint was progression-free survival (PFS). Results: After PSM, 120 patients were included in each group with balanced characteristics. The ivonescimab group had significantly longer median PFS (7.6 vs 5.9 months, HR=0.77, 95% CI 0.60– 0.997, P=0.042) and overall survival (18.0 vs 15.1 months, HR=0.72, 95% CI 0.56– 0.94, P=0.010), as well as higher objective response rate (45.0% vs 28.3%, P=0.007) and disease control rate (91.7% vs 81.7%, P=0.023). In exploratory subgroup analysis, patients with PD-L1 TPS≥ 50% derived the greatest benefit. Safety profiles were comparable between groups. Multivariate analysis confirmed ivonescimab plus chemotherapy as an independent protective factor for both survival endpoints. Conclusion: Compared with bevacizumab plus chemotherapy, ivonescimab plus chemotherapy prolongs survival with manageable safety in this population, and may serve as a potential second-line treatment option. However, given the retrospective observational design, these findings require further prospective validation.