Efficacy and safety of immune checkpoint inhibitors combined with chemotherapy versus bevacizumab combined with chemotherapy in first-line treatment of driver gene-negative advanced non-squamous non-small cell lung cancer: a single-center retrospective study.

PURPOSE: To compare the efficacy and safety of immune checkpoint inhibitors (ICIs) versus bevacizumab (both combined with chemotherapy) for first-line treatment of driver gene-negative advanced non-squamous non-small cell lung cancer (NSCLC). METHODS: This single-center retrospective study enrolled 194 patients with driver gene-negative advanced non-squamous NSCLC treated at our hospital from May 1, 2019, to May 1, 2025: 79 received ICIs plus chemotherapy, and 115 received bevacizumab plus chemotherapy. Both groups received 4-6 cycles of combination therapy followed by maintenance therapy until disease progression or the end of the study. The primary endpoint was progression-free survival (PFS), and secondary endpoints included objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). RESULTS: Short-term efficacy: ORR was significantly higher in the ICIs plus chemotherapy group than in the bevacizumab plus chemotherapy group (41.77% vs 26.09%, P = 0.022), while DCR showed no statistically significant difference between groups (84.81% vs 79.13%, P = 0.317). Survival benefit: Median PFS was 14.330 months in the ICIs plus chemotherapy group, which was superior to 9.60 months in the bevacizumab plus chemotherapy group (P = 0.014). Safety: The ICIs plus chemotherapy group had a higher incidence of thyroid dysfunction (8.86% vs 0%, P = 0.002), immune-related pneumonitis (3.80% vs 0%, P = 0.066) and immune-related hepatitis (5.06% vs 0%, P = 0.026); the bevacizumab plus chemotherapy group had a higher incidence of proteinuria (7.83% vs 0%, P = 0.012) and hypertension (6.96% vs 0%, P = 0.022). Other AEs were comparable between the two groups. Subgroup analysis: Higher disease progression risk was observed in the bevacizumab plus chemotherapy group for patients with PD-L1 high expression (HR = 3.731, P = 0.039), indicating this population benefits more from ICIs plus chemotherapy. Higher progression risk was seen in the ICIs plus chemotherapy group for males (HR = 2.410, P = 0.015), ever-smokers (HR = 2.215, P = 0.047), patients with ECOG score 0-1 (HR = 1.762, P = 0.032) and patients without bone metastasis (HR = 2.112, P = 0.036), suggesting these subgroups are more likely to benefit from bevacizumab plus chemotherapy. CONCLUSIONS: For patients with driver gene-negative advanced non-squamous NSCLC, ICIs combined with chemotherapy are superior to bevacizumab combined with chemotherapy in terms of short-term efficacy and progression-free survival, with manageable but distinct adverse event profiles.