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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