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

Shohei Hamada,Tokunori Ikeda,Kazuhiko Fujii,Megumi Inaba,Hidenori Ichiyasu,Takeshi Yoshinaga,Sho Saeki,Kimitaka Akaike,Koichi Saruwatari,Yusuke Tomita,Kosuke Kashiwabara,Tomoki Sadamatsu,Naomi Hirata,Hiroko Okabayashi,Nahoko Sato

doi:10.1186/s12890-019-0838-2

Abstract

BackgroundAcute 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.MethodsWe 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.ResultsThe 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).ConclusionsThe addition of Bev to chemotherapy regimens may reduce the risk of chemotherapy-related AE-ILD in patients with lung cancer.

Highlights

Acute exacerbation of interstitial lung disease (AE-Interstitial lung disease (ILD)) is the most serious complication in lung cancer patients with pre-existing ILD receiving chemotherapy
The most common regimen used for first-line chemotherapy was the combination of carboplatin (CBDCA) plus pemetrexed (PEM) in both groups
We examined the cumulative incidence of Acute exacerbation of interstitial lung disease (AE-ILD) during subsequent chemotherapy beyond first-line chemotherapy

Summary

Introduction

Acute exacerbation of interstitial lung disease (AE-ILD) is the most serious complication in lung cancer patients with pre-existing ILD receiving chemotherapy. We examined the effect of Bev on reducing AE-ILD risk in non-squamous non-small cell lung cancer (NSCLC) patients receiving chemotherapy. Kudoh et al [3] reported that pre-existing ILD is a strong risk factor for AE-ILD in patients with non-small cell lung cancer (NSCLC; odds ratio, 4.80–25.27) compared with those without ILD. Increasing levels of plasma VEGF in acute respiratory distress syndrome (ARDS) are associated with a worse outcome [10], and in animal models, inhibition of VEGF using a soluble receptor to VEGF reduces bleomycin-induced lung injury and fibrosis [11]. The influence of inhibiting function of VEGF on AE-ILD has not been fully examined

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