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

Abstract

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).