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 |