Treatment‐Related Adverse Events of Antibody‐Drug Conjugate Monotherapy in Non‐Small Cell Lung Cancer: A Systematic Review and Meta‐Analysis

Background Antibody‐drug conjugates (ADCs) have demonstrated promising efficacy in several prospective clinical studies, offering new possibilities for the treatment of non‐small cell lung cancer (NSCLC). Consequently, understanding the toxicity profile associated with ADCs is of critical importance. Methods A comprehensive search was performed across PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for studies on ADC monotherapy in NSCLC. Data extraction prioritized treatment‐related adverse events (TRAEs), drug‐related adverse events (AEs), or treatment‐emergent adverse events (TEAEs). Incidences were pooled using a random‐effects model. Results Thirteen studies including 1566 NSCLC patients were analyzed. The pooled incidence of all‐grade TRAEs was 93.67%. Grade ≥ 3 TRAEs occurred in 38.74%, and serious TRAEs in 15.89%. Discontinuation and mortality rates were 9.52% and 0.63%. Hematologic toxicity was common among grade ≥ 3 TRAEs. Additionally, 20 fatal TRAEs were mainly associated with respiratory toxicity. Subgroup analysis for adverse events of special interest (AESIs) showed that Trastuzumab deruxtecan was more likely to cause grade ≥ 3 pneumonitis or interstitial lung disease (ILD), while TROP2‐targeted ADCs were prone to high‐grade stomatitis and ocular toxicity. Conclusion The overall incidence of TRAEs with ADC monotherapy in NSCLC is high, but most are Grade 1 or 2 and overall safety is manageable. Importantly, fatal TRAEs were mainly respiratory in this study, requiring clinical vigilance. Grade ≥ 3 AESIs should also be closely monitored. Registration This study was registered at INPLASY (ID: INPLASY2023120046).