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

Abstract

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.