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Table 3 Anti-HER2 ADCs treatment-related grade ≥ 3 adverse events occurring in > 2% of patients

From: Implementing antibody-drug conjugates (ADCs) in HER2-positive breast cancer: state of the art and future directions

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
  1. This table includes all the ADCs discussed in this review (approved and under development) for which toxicity data were available at the time of the last editing (April 2021)