Background: Antibody-drug conjugates (ADCs) combine the targeted nature of monoclonal antibodies with the potent efficacy of small-molecule cytotoxic drugs. However, they also carry unique safety risks, including lung toxicity.
Objective: To conduct a systematic review and analysis of ADC-related interstitial lung disease (ILD) incidence, characteristics, and risk factors to optimize safe and effective clinical use.
Design: ADC-related ILD reports from the FDA Adverse Event Reporting System (FAERS) database between January 2014 and March 2023 were analyzed.
Methods: ADC-related ILD reports were retrieved from the FAERS database. Statistical analyses were conducted using reporting odds ratio (ROR) and information components (ICs). The lower limit of the 95% confidence interval (CI) was set for ROR (ROR025) >1 or IC (IC025) >0, and statistical significance was determined based on a minimum of three reports.
Results: The study analyzed the statistical data on ADC-induced ILDs (1277 cases). Trastuzumab deruxtecan was reported to be the most frequent (38.4%). Among the 33 preferred terms (PTs) in standardized MedDRA queries (SMQ) = "Interstitial lung disease," the three most common were as follows: ILD (40.6%), pneumonitis (27.9%), and acute respiratory distress syndrome (ARDS) (7.6%). Trastuzumab deruxtecan showed the strongest association with ILD (PT) and pneumonitis, whereas ARDS was associated with four different drugs. The median time to onset of ADC-related ILDs was 51 days (interquartile range (IQR), 16-196), with ARDS having the earliest median time to onset at 15 days (IQR, 6-52). The onsets of pneumonitis, ILD, lung infiltration, and pulmonary toxicity were similar. More than 26% of ADC-related ILD cases result in death, with ARDS having the highest mortality rate of 65.0%.
Conclusion: ADCs are associated with an increased risk of pulmonary adverse events, such as ILDs, with significant differences between drugs and varying mortality rates for different adverse events, necessitating distinct monitoring and appropriate management.
Keywords: FAERS database; antibody–drug conjugate; interstitial lung disease; pharmacovigilance analysis; real-world study.
A study on the risk of lung diseases associated with antibody-drug conjugates (ADCs) cancer treatmentWhy was this study important? Antibody drug conjugates (ADCs) represent a new drug for cancer treatment, using a “targeting device” (antibody) to locate the cancer cells and “powerful medicine” (chemotherapy drug) to destroy them. However, this method can sometimes cause lung injuries. Understanding how common these lung problems are, what they look like, and who is most susceptible is crucial for ensuring patient safety and effective treatment. What did researchers do? They examined reports related to ADC-induced lung problems in a U.S. system that records drug side effects (which we’ll call the FDA Adverse Event Reporting System) from January 2014 to March 2023. What were the findings? Among the 1,277 cases of lung problems caused by ADCs, Trastuzumab deruxtecan, an ADC drug, was the most common. These lung problems mainly involved three conditions: inflammation in the lungs (pneumonia), hardening and disease of lung tissue (interstitial lung disease), and sudden respiratory distress (acute respiratory distress syndrome). Among them, acute respiratory distress syndrome had the highest mortality rate. What does this mean? Using ADCs for cancer treatment may pose a risk of lung problems, with varying degrees of risk and severity depending on the specific drug. Therefore, it is necessary to closely monitor and manage patients when using these treatments.