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Research Article: Clinical exploration of first-line therapy in metastatic lung adenocarcinoma patients with negative or low PD-L1 expression: a retrospective cohort study

Date Published: 2026-06-03

Abstract:
Either Programmed cell death protein 1 (PD-1)/Programmed cell death-Ligand protein 1 (PD-L1) inhibitors plus chemotherapy or anti-angiogenic agents plus chemotherapy has become first-line therapy in negative or low PD-L1 patients with driver-gene-negative metastatic lung adenocarcinoma. PD-1/PD-L1 inhibitors plus anti-angiogenic agents with chemotherapy is also an option. However, there are no large studies evaluating the advantages and disadvantages of the three treatment strategies. Totally 163 stage IV lung adenocarcinoma patients with negative or low PD-L1 expression who received first-line treatment at Nanjing Medical University Affiliated Cancer Hospital from November 1, 2019 to December 1, 2023 were analyzed. We evaluated the difference in efficacy of multiple treatment regimens. 57 patients received anti-angiogenic agents plus chemotherapy (AC group), 69 patients received PD-1/PD-L1 inhibitors plus chemotherapy (PC group) and 37 patients received PD-1/PD-L1 inhibitors plus anti-angiogenic agents with chemotherapy (APC group). The median progression-free survival (mPFS) was 6.3 months, 8.7 months and 13.8 months in AC, PC and APC group, respectively. The APC group significantly prolonged patients’ PFS compared to the AC and PC groups. APC group and PC group had no significant difference in overall survival (OS) compared to AC group. Subgroup analysis showed that APC group significantly lowered the risk of disease progression compared to AC group in the PD-L1-negative subgroup. The incidence of grade 3–4 adverse events (AEs) was similar in three groups. Among the first-line treatment regimens for metastatic lung adenocarcinoma patients with negative or low PD-L1 expression, PD-1/PD-L1 inhibitors plus anti-angiogenic agents with chemotherapy showed significant benefit in PFS compared to anti-angiogenic agents plus chemotherapy and PD-1/PD-L1 inhibitors plus chemotherapy.

Introduction:
Either Programmed cell death protein 1 (PD-1)/Programmed cell death-Ligand protein 1 (PD-L1) inhibitors plus chemotherapy or anti-angiogenic agents plus chemotherapy has become first-line therapy in negative or low PD-L1 patients with driver-gene-negative metastatic lung adenocarcinoma. PD-1/PD-L1 inhibitors plus anti-angiogenic agents with chemotherapy is also an option. However, there are no large studies evaluating the advantages and disadvantages of the three treatment strategies.

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