Interstitial lung disease associated with novel anticancer agents in non-small cell lung cancer: a pharmacovigilance...

Some novel anticancer agents are associated with drug-induced interstitial lung disease (ILD), a critical and potentially fatal adverse event. Lung cancer patients appear particularly susceptible, yet the risk and clinical characteristics remain incompletely analyzed.

To comprehensively evaluate ILD risk and characteristics induced by novel anticancer agents in non-small cell lung cancer (NSCLC) using large-scale real-world data.

A retrospective pharmacovigilance study based on spontaneous adverse event reports.

Data from 2014 to 2024 were extracted from the Food and Drug Administration Adverse Event Reporting System (FAERS). Reports of NSCLC patients who developed ILD during treatment with FDA-approved novel anticancer agents (immune checkpoint inhibitors, targeted therapies, antibody-drug conjugates). The reporting odds ratio (ROR) was used to assess the disproportionate reporting signals for each drug. Statistical significance was defined when the lower 95% confidence interval (CI) exceeded 1 with at least three reports.

A total of 4712 NSCLC cases were analyzed. Eight agents were identified with positive signals for ILD: ROR and 95% CI for nivolumab was 1.28 (1.20-1.38), pembrolizumab 1.47 (1.36-1.59), durvalumab 7.38 (6.90-7.89), atezolizumab 1.25 (1.12-1.39), ipilimumab 1.96 (1.74-2.21), tremelimumab 3.58 (1.97-6.50), trastuzumab-deruxtecan 3.14 (2.29-4.30), osimertinib 1.12 (1.03-1.23). The median onset time was 33 days, with 48.59% of ILD events occurring within the first month. The fatal cases experienced a significantly shorter onset time than non-fatal cases. Older age, male sex, and lower body weight were identified as factors affecting ILD, whereas lower body weight, male sex, and a higher number of concomitant drugs were linked to increased mortality.

Our study identifies positive signals for ILD with eight novel antineoplastic agents in NSCLC, including nivolumab, pembrolizumab, durvalumab, atezolizumab, ipilimumab, tremelimumab, trastuzumab-deruxtecan, and osimertinib, highlights the importance of monitoring during the first month of therapy, and identifies older male patients with lower body weight as a high-risk group.