Table 4 Anti-HER2 ADC toxicities of special interest
| Toxic effect | ADCs | Frequency | Possible mechanism |
|---|---|---|---|
|
Interstitial lung disease Pneumonitis |
T-Dxd [46] ARX788 [25] |
Any grade: 15.5% Grade 3:1% Grade 4: 0.1% Grade 5: 2.4% Any grade: 19.6% Grade 3: 2% |
Alveolar inflammation and fibrosis due to off-target activity of DXd Unknown |
| LVEF drop |
T-DM1 [44] T-Dxd [15] |
Any grade: 2% Grade 3–4: 0.7% Any grade: 1.6% Grade 3–4: 0.5% | Target-related: morphologic and functional potentially reversible damage to cardiomyocytes inducted by anti HER2-Ab |
| Prolonged QT | T-Dxd [15] |
Any grade: 4.9% Grade 3–4: 1.1% | Unknown |
| Ocular toxicities |
SYD985 [18] A166 [19] ARX788 [25] |
Conjunctivitis All grades: 31% Grade 3/4: 3% Keratitis: All grades: 19% Grade 3/4: 2% Overall and any grade: 80% Overall and any grade: 41.2 % | Systemic releasing of the payload |