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Table 4 Anti-HER2 ADC toxicities of special interest

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

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
  1. All patients included in these trials received prior anti-HER2 therapies in metastatic and/or adjuvant setting