Immune Checkpoint Inhibitors More Effective vs Bevacizumab in Nonsquamous NSCLC

The efficacy of immune checkpoint inhibitors (ICIs) combined with chemotherapy was high in advanced driver gene–negative nonsquamous non–small cell lung cancer (NS-NSCLC) when tested against bevacizumab combined with chemotherapy, according to a new study published in Journal of Multidisciplinary Healthcare.¹ The use of ICIs also had less impact on immune function in patients using the treatment.

Immune checkpoint inhibitors were more effective in treating NS-NSCLC compared with bevacizumab. | Image credit: Sebastian Kaulitzki - stock.adobe.com

NSCLC is the most common form of lung cancer in the world, at 80% to 85% of all diagnosed lung cancers.² Poor prognosis makes it a serious diagnosis that has low 5-year survival rates. ICIs are a means of treating lung cancer that help restore T-cell activity and improve immune responses, which could help with progression-free survival (PFS) and overall survival (OS). This study¹ aimed to compare ICIs plus chemotherapy with bevacizumab plus chemotherapy, specifically focusing on safety, survival outcomes, and efficacy to improve clinical decisions regarding treatment for NS-NSCLC.

The retrospective study collected data from patients who received treatment at the Third Affiliated Hospital of Wenzhou Medical University between October 2015 and January 2022. Participants were included if they were aged 18 to 75 years, were diagnosed with driver gene–negative NS-NSCLC, had an estimated survival time of 6 months or more, had classified stage IV cancer, and had normal comprehension skills. Patients with acute heart disease or other severe comorbidities, who were pregnant, had major surgery within 6 months of enrollment, or had a history of or active tuberculosis, immune system diseases, presence of other malignancies, or allergies to treatment used in the study were excluded. All participants were split into 2 groups to receive either ICIs or bevacizumab.

Tumor status was assessed before each treatment cycle. All patients received pemetrexed with cisplatin every 21 days. The groups received intravenous (IV) ICIs or bevacizumab on the first day of their chemotherapy cycle. Treatment efficacy was evaluated after 2 to 3 consecutive treatment cycles, specifically looking into serum tumor markers, adverse reactions, and survival status.

There were 199 patients included in the study, of whom 103 used ICIs plus chemotherapy. The 2 groups had no significant outcome differences attributed to gender, age, smoking history, body mass index, or primary tumor site. The objective response rate for ICIs was significantly higher compared with bevacizumab (59.2% vs 36.5%).

The median PFS was 11.13 months (95% CI, 8.02-14.25) in those who took ICIs compared with 7.37 months (95% CI, 5.69-9.05) in those who took bevacizumab. The median OS was also slightly longer in those who took ICIs (20.87 months; 95% CI, 18.73-23.01) compared with those who took bevacizumab (18.42 months; 95% CI, 15.72-21.08). All adverse reactions were resolved after treatment, with most adverse effects being grades 1 or 2. A total of 26.2% of those using ICIs experienced adverse effects.

There were some limitations to this study. Selection bias was possible due to the retrospective and nonrandomized design of the study. Differences between the 2 groups in gender and age approached significance, but confounding variables were not adjusted for in a multivariate analysis. Also, the generalizability was limited due to the small sample size and the single-center design, and patients’ genetic background, tumor mutational burden, or PD-L1 expression could influence the efficacy of ICIs.

The researchers concluded that ICIs were more effective in treating NS-NSCLC compared with bevacizumab. ICIs led to improved PFS and OS and had a comparable safety profile to bevacizumab.

“These findings support the use of ICIs plus chemotherapy as a promising and safe first-line treatment strategy in this patient population,” wrote the authors. “However, given the limitations of our single-center, retrospective design, further prospective multicenter studies are needed to validate these results and guide personalized treatment approaches.”

References

1. Chen W, Dai Q, Ye Z, Huang Y. Comparison of the efficacy of immune checkpoint inhibitors combined with chemotherapy versus bevacizumab combined with chemotherapy in advanced driver gene-negative non-squamous non-small cell lung cancer: a retrospective study. J Multidiscip Healthc. 2025;18:4279-4289. doi:10.2147/JMDH.S535853

2. What is lung cancer? American Cancer Society. Updated January 29, 2024. Accessed August 6, 2025. https://www.cancer.org/cancer/types/lung-cancer/about/what-is.html