Bevacizumab Study Shows Reduced ILD Risk in Advanced NSCLC
Posted: Thursday, May 7, 2026
A nationwide real-world study led by Chikako Iwai, MD, of the Department of Clinical Epidemiology and Health Economics, The University of Tokyo, evaluated the safety profile of bevacizumab in advanced nonsquamous non–small cell lung cancer (NSCLC), addressing concerns about treatment-related interstitial lung disease (ILD). As reported in Lung Cancer, the researchers aimed to clarify whether bevacizumab influences ILD risk and short-term outcomes in patients receiving first-line platinum-based chemotherapy.
Study Methods
Using the Japanese Diagnosis Procedure Combination database (2011–2023), the researchers compiled a large, retrospective cohort of 47,433 patients with stage III to IV nonsquamous NSCLC treated with platinum plus pemetrexed, with (n = 12,101) or without (n = 35,332) bevacizumab. A target trial emulation framework was used to approximate a randomized clinical trial, and propensity score overlap weighting ensured balance across baseline characteristics.
The study design allowed inclusion of patient populations often excluded from clinical trials, such as older adults, those with prior ILD, and individuals with comorbidities or brain metastases. The primary endpoint was ILD requiring corticosteroid treatment (excluding dexamethasone and betamethasone) within 180 days of chemotherapy initiation, while secondary outcomes included 180-day mortality, mortality within 30 days after ILD onset, and venous thromboembolism (VTE). Because the research relied on a database composed of inpatient discharge summaries and claims, events occurring outside the hospital were not recorded
Key Takeaways
Bevacizumab use was associated with significantly improved outcomes. The risk of ILD was reduced by 25% compared with chemotherapy alone (subdistribution hazard ratio [SHR] = 0.75, 95% confidence interval [CI] = 0.67–0.84). Additionally, bevacizumab was linked to lower 180-day all-cause mortality (HR = 0.61, 95% CI = 0.57–0.66) and reduced mortality within 30 days after ILD onset (HR = 0.71, 95% CI = 0.57–0.88). These findings were consistent across clinically relevant subgroups, including age, immune checkpoint inhibitor use, and prior ILD history. The risk of VTE did not differ significantly between groups.
According to the study authors, bevacizumab’s inhibition of vascular endothelial growth factor (VEGF) may underlie the observed protective effect, potentially reducing pulmonary inflammation, vascular permeability, and fibrosis. These mechanistic insights align with preclinical and clinical evidence supporting VEGF’s role in lung injury and fibrotic pathways. The findings highlight a potential dual benefit of bevacizumab—antitumor activity and mitigation of treatment-related pulmonary toxicity—particularly relevant for high-risk populations underrepresented in trials.
The investigators concluded: “In patients with advanced non-squamous NSCLC receiving first-line platinum-based chemotherapy, bevacizumab use was associated with lower risks of ILD and short-term mortality, without increased VTE risk.”
DISCLOSURE: For full disclosures of the study authors, visit lungcancerjournal.info.
