Protective effect of bevacizumab on chemotherapy-related acute exacerbation of interstitial lung disease in patients with advanced non-squamous non-small cell lung cancer

Abstract

Background Acute exacerbation of interstitial lung disease (AE-ILD) is the most serious complication in lung cancer patients with pre-existing ILD receiving chemotherapy. The role of vascular endothelial growth factor (VEGF) in pathogenesis of AE-ILD is conflicting. The influence of bevacizumab (Bev), a monoclonal antibody against VEGF, on lung cancer patients with pre-existing ILD remains unclear. We examined the effect of Bev on reducing AE-ILD risk in non-squamous non-small cell lung cancer (NSCLC) patients receiving chemotherapy. Methods We analysed incidence of AE-ILD and outcomes of 48 patients with advanced non-squamous NSCLC with ILD who received first-line chemotherapy with (Bev group, n = 17) and without (non-Bev group, n = 31) Bev between July 2011 and July 2016. Gray’s test, which was competing risk analysis during the study period, was performed for both groups. Results The most common regimen used for first-line chemotherapy was the combination of carboplatin plus pemetrexed (PEM) in both groups. The incidences of chemotherapy-related AE-ILD 120 days after first-line chemotherapy initiation were significantly lower in the Bev than in the non-Bev groups (0% vs. 22.6%, p = 0.037, Gray’s test). However, there were no differences in development of progressive disease of lung cancer and other events as the competing risk factors of AE-ILD between the two groups. Only patients receiving PEM-containing regimens also showed a significant difference in the incidence of AE-ILD between the two groups ( p = 0.044). The overall-cumulative incidence of AE-ILD during the first-line and subsequent chemotherapy was 29.2% (14 of the 48). The median progression-free survival was significantly longer in the Bev than in the non-Bev groups (8.0 vs. 4.3 months, p = 0.026). Conclusions The addition of Bev to chemotherapy regimens may reduce the risk of chemotherapy-related AE-ILD in patients with lung cancer. Electronic supplementary material The online version of this article (10.1186/s12890-019-0838-2) contains supplementary material, which is available to authorized users.

Vaccines and Drug Therapeutics to Lock Down Novel Coronavirus Disease 2019 (COVID-19): A Systematic Review of Clinical Trials

“…VEGF receptors are present on endothelial cells that produce various inflammatory and epithelial cells acting as potential vascular permeability inducer. Prior studies have identified increased levels of VEGF in patients with ARDS [26,27]. Given the causal link between ARDS and increased pulmonary edema and vascular permeability, the researchers believed that bevacizumab might be a promising therapeutic agent in severe cases of COVID-19.…”

Glasgow Prognostic Score predicts chemotherapy‐triggered acute exacerbation‐interstitial lung disease in patients with non‐small cell lung cancer

“…However, to date, no large‐scale Phase 3 studies of pharmacotherapy have been conducted in NSCLC patients with ILD. Moreover, previous studies had sample sizes ranging from 21 to 114 patients, 1–7,29–32,34,38 and many of them were as large as our study. Second, patients with ILD of a known etiology were excluded from this study because these diseases affect elevated CRP and/or hypoalbuminemia.…”

“…AE‐ILD included all acute respiratory events with newly appearing, bilateral ground‐glass opacification (GGO) and/or interstitial shadows that could not be explained by infectious disease, cardiac failure, or fluid overload 28–32 . AE‐ILD triggered by chemotherapy was described as the onset of AE within four weeks of the last administration of chemotherapy 29–32 …”

The Efficacy and Safety of First-Line Chemotherapy in Patients With Non-small Cell Lung Cancer and Interstitial Lung Disease: A Systematic Review and Meta-Analysis

“…The subgroup analysis based on total AE-ILD rate with 25% as the cut-off point revealed that higher AE-ILD rate was associated with a worse 1-yOS rate (48 vs. 36%, p = 0.013) ( Table 2 ). A study ( 44 ) reported that first-line chemotherapy combined with bevacizumab could reduce the incidence of chemotherapy-related AE-ILD in patients with NSCLC-ILD (0 vs. 22.6%, p = 0.037), At the same time, a phase II trial ( 45 ) that examines whether nintedanib combined with carboplatin plus nab-paclitaxel can prolong the interval to acute exacerbation of IPF is underway. In the future, those studies may provide new options for the treatment of patients with NSCLC-ILD.…”