Treatment-related adverse events associated with HER2-Targeted antibody-drug conjugates in clinical trials: a systematic review and meta-analysis

Data reproducibility issues on evidence synthesis of adverse events associated with HER2-targeted antibody–drug conjugates

“…After careful scrutiny of the original data sources of all 13 randomized controlled trials involved, we found numerous data extraction errors in Fu's meta-analysis, 2 rendering their meta-analysis less reliable.…”

“…Therefore, it is important to figure out whether or not there are also data extraction errors in a new published systematic review and meta-analysis on adverse events (AEs), such as the meta-analysis of AEs of HER2-targeted antibody–drug conjugates (ACDs) presented recently. 2 …”

“… 2 To name only a few, the correct number of all-grade AEs, grade ≥3 AEs, and serious AEs in Verma 2012 3 were 470, 200, and 76, respectively, rather than 474, 233, and 91 used for Fu's meta-analysis. 2 Furthermore, the correct number of discontinuation due to AEs in Thungappa et al. 4 was zero rather than 3 used for Fu's meta-analysis.…”

“… 4 was zero rather than 3 used for Fu's meta-analysis. 2 Also, the accurate number of grade ≥3 AEs in Tolaney 2021 5 should be 61 rather than 62 used.…”

“…Second, Fu and colleagues 2 failed to distinguish between treatment-emergent adverse events (TEAEs) and drug-related TEAEs in their Table 1. In the study by Cortés 2022 (Cortés’ Table S5), 6 in trastuzumab deruxtecan (T-DXd) group, TEAEs for all-grade AEs, grade ≥3 AEs, serious AEs were reported to be 256, 134, 49, respectively, and drug-related TEAEs for all-grade AEs, drug-related grade ≥3 AEs, drug-related serious AEs were 252, 116, 28, respectively; however, the authors of the systematic review extracted the number 252 (drug-related TEAE), 134 (TEAE), 49 (TEAE).…”