Table 3 Anti-HER2 ADCs treatment-related grade ≥ 3 adverse events occurring in > 2% of patients
| Toxic effect | ADCs | Frequency | Possible mechanism |
|---|---|---|---|
| Thrombocytopenia |
T-DM1 [7] T-DXd [15] |
14.3% 4.3% |
DM1-induced impairment of megakaryocytes differentiation Bone marrow toxicity of payload |
| Neutropenia |
T-DM1 [7] T-DXd [15] SYD985 [18] RC48-ADC [23] ALT-P7 [24] |
2.4% 20% 14% 10% 14% | Bone marrow toxicity of payloads |
| Anemia |
T-DM1 [7] T-DXd [15] |
3.8% 8.6% | Bone marrow toxicity of payloads |
| Leukopenia | RC48-ADC [23] | 6.7% | Bone marrow toxicity of payloads |
| Decreased lymphocyte count | T-DXd [15] | 8.1% | Bone marrow toxicity of payloads |
| Fatigue |
T-DM1 [7] T-DXd [15] SYD985 [18] PF-06804103 [28] |
2.4% 6% 3% 5.7% | Unknown |
| Arthralgia | PF-06804103 [28] | 5.7% | Unknown |
|
Increased ALT Increased ALT |
T-DM1 [7] RC48-ADC [23] RC48-ADC [23] |
15% 3.3% 3.3% | Cytotoxic activity on the hepatocytes (clearance of T-DM1 depends mainly on the hepatobiliary and gastrointestinal route) |
| Nausea | T-DXd [15] | 7.6% | Off-target effect of the payload |
| Vomiting | T-DXd [15] | 4.3% | Off-target effect of the payload |
| Diarrhea | T-DXd [15] | 2.7% | Off-target effect of the payload |
| Peripheral neuropathy |
T-DM1 [49] PF-06804103 [28] |
13% 5.7% |
Degeneration of the axons, time-dependent, due to the DM1 component Systemic release of payload |