Incidence and prognostic factors in severe drug-induced interstitial lung disease caused by antineoplastic drug therapy in the real world

Abstract

Purpose Investigate the frequency and prognostic factors of severe drug-induced interstitial lung disease (DILD) caused by antineoplastic drugs regardless of cancer types or type of drugs. Methods From 2014 to 2018, we reviewed patients with a history of antineoplastic agents administration in the real-world database of our hospital's electronic medical record and extracted patients who experienced "severe" DILD, requiring hospitalization with treatment or developed during hospitalization and required treatment. We collected patients' backgrounds, clinical and radiological features, laboratory data, treatment, and survival outcomes. Results 19,132 cancer patients received antineoplastic drug therapy during the study period, and 120 (0.62%) experienced severe DILD. The incidence of severe DILD in patients with thoracic cancer was highest among the patients included in this analysis (2.52% vs. 0.34% other cancers). Diffuse alveolar damage (DAD) pattern on CT was associated with higher mortality in patients with severe DILD compared with non-DAD pattern (hazard ratio [HR], 11.24; 95% CI, 4.82–26.2). Multivariate analysis revealed that the DAD pattern at diagnosis as severe DILD (HR, 3.59; 95% CI, 1.17–11.03), concurrent/previous interstitial lung disease (HR, 3.20; 95% CI, 1.27–8.10), and ECOG performance status of 2–4 (HR, 3.81; 95% CI, 1.10–13.17) were independent risk factors for mortality in patients with severe DILD. Conclusions The frequency of severe DILD was highest in patients with thoracic cancer. The DAD pattern was associated with a poor outcome. From the perspective of DILD, special attention should be paid when administering antineoplastic agents to patients with thoracic cancer.

The incidence of drug-induced interstitial lung disease caused by epidermal growth factor receptor tyrosine kinase inhibitors or immune checkpoint inhibitors in patients with non-small cell lung cancer in presence and absence of vascular endothelial growth factor inhibitors: a systematic review

“…However, the clinical questions addressed in each systematic review differed. ILD induced by anti-cancer agents is known to occur more frequently in lung cancer than in other solid tumors ( 23 , 58 – 62 ). Therefore, we concluded that the addition of VEGF/VEGFR inhibitors could reduce the incidence of drug-induced ILD caused by EGFR-TKI or ICI in patients with NSCLC.…”

Analysis of 12 cases of antineoplastic agents-induced interstitial lung disease

“…Non-drug factors: ① Age; the elderly are more likely to have serious adverse reactions due to reduced renal excretion function and reduced liver blood flow, as well as changes in overall metabolic function. ② Sex; Kaku et al (2022) found that male sex was associated with a higher risk of severe DILD-related death. Frontiers in Pharmacology frontiersin.org risk of DILD of patients who smoked previously is higher than those not (Ando et al, 2006).…”

Pan-cancer assessment of antineoplastic therapy-induced interstitial lung disease in patients receiving subsequent therapy immediately following immune checkpoint blockade therapy

“…The similar influence of prior immunotherapy on the frequency of immune-mediated reactions to subsequent kinase inhibitors has been observed in several oncogene-driven NSCLCs and melanoma [ 13 – 17 ]. However, although drug-induced ILD (DIILD) could be caused by any type of antineoplastic agent [ 18 ], it remains unknown whether the incidence and severity of DIILD are affected by immediately prior ICI therapy. This clinical question is becoming more crucial because upfront IO therapies using ICIs have become the standard of care for multiple types of cancers, and cancer patients are therefore more likely than before to be exposed to subsequent antineoplastic agents after receiving ICIs.…”