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

Jianxi Zhou,1– 3,* Yinghao Wang,4,* Kang Wen,1,2 Chun Huang,1,2 Dingzhi Huang,1,2 Tingting Qin,1,2 Mengjie Li,1,2 Yudong Su,1,2 Yunchuan Sun,3 Peng Chen1,21Department of Thoracic Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Tianjin Lung Cancer Center, Tianjin, People’s Republic of China; 2Department of Thoracic Oncology, State Key Laboratory of Druggability Evaluation and Systematic Translational Medicine, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People’s Republic of China; 3Department of Head, Neck and Thoracic Oncology, Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine-Hebei, Cangzhou, Hebei, People’s Republic of China; 4Department of General Surgery II, The Fifth People’s Hospital of Hengshui City, Hengshui, Heibei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng Chen, Email Chenpyxz@163.comObjective: 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.Keywords: lung adenocarcinoma, drug resistance, neoplasm, ivonescimab, bevacizumab, antineoplastic combined chemotherapy protocols