Evaluation of Durvalumab-induced Lung Toxicity Using a Spontaneous Reporting Database

Abstract

Background/aim: Durvalumab is a human monoclonal antibody targeting programmed cell death ligand 1. It is classified as an immune checkpoint inhibitor and has shown high efficacy as maintenance therapy after chemoradiation for stage III non-small-cell lung cancer and as the primary treatment for small-cell carcinoma. Interstitial lung disease is the most common adverse event leading to durvalumab discontinuation. Hence, this study was aimed at assessing the incidence and timing of durvalumab-induced lung toxicity by using the Japanese Adverse Drug Event Report (JADER) database.

Patients and methods: Adverse Adverse events (AEs) of durvalumab reported from August 2018 to March 2021 were extracted. Data on lung AEs were analysed to estimate relative risk using reporting odds ratios (RORs) and 95% confidence interval (CIs). Furthermore, the times of onset of signs of lung toxicity were also estimated.

Results: Overall, 2,162 AEs attributable to durvalumab were obtained. Of these, 1,239 were lung toxicities, the most common among which were pneumonia, interstitial lung disease, and radiation-associated pneumonitis. The corresponding RORs (95% CIs) for these signs were 271.50 (244.79-301.11), 5.96 (5.29-6.72), and 713.21 (595.04-854.85), respectively. The median (interquartile range) times of onset were 32.5 (28.5-35.5), 31.5 (28.5-41.5), and 28.5 (28.5-30.5) days, respectively.

Conclusion: Among the AEs of durvalumab, pneumonia, interstitial lung disease, and radiation-induced pneumonitis were associated with high RORs, suggesting a strong causal relationship with durvalumab. Interstitial lung disease and radiation-induced pneumonitis most often occurred approximately 30 days after treatment initiation, suggesting that monitoring for adverse events during this period is important.

Keywords: Durvalumab; Japanese Adverse Drug Event Report database; lung toxicity; signal detection; time to onset.