Table 3.

ADC-associated adverse events.

Agent	Trial (n-Treatment Arm)	Most Common Side Effects (Any Grade)	Grade ≥ 3 Adverse Events	Agent Interruption/Discontinuation	Grade 5 (Deaths)	Ref.
T-DM1	KATHERINE trial (n = 740)	Any adverse event 98.8%, fatigue 49.5%, nausea 41.6%, thrombocytopenia 28.5%, increased AST 28.4%, headache 28.4%, arthralgia 25.9%, radiation-related skin injury 25.4%, increased ALT 23.1%, epistaxis 21.5%, peripheral sensory neuropathy 18.6%, constipation 17%, myalgia 15.4%, hot flashes 12.8%	Any event 25.7%; thrombocytopenia 5.7%, hypertension 2.0%, radiation-related skin injury 1.4%, peripheral sensory neuropathy 1.4%, neutropenia is 1.2%, hypokalemia 1.2%, fatigue 1.1%, anemia 1.1%	Any event 18%; thrombocytopenia 4.2%, hyperbilirubinemia 2.6%, elevated AST 1.6%, elevated ALT 1.5%, peripheral neuropathy 1.5%, decreased ejection fraction 1.2%	0.1%	[22]
	TH3RESA (n = 403)	Nausea 35%, fatigue 29%, headache 24%, vomiting 18%, asthenia 18%, pyrexia 20%, epistaxis 16%, arthralgia 15%, thrombocytopenia 15%, constipation 22%, cough 19%, lack of appetite 16%, myalgia 11%, increased AST 10%, dyspnea 9%, anemia 8%, abdominal pain 6%, rash 6%, neutropenia 5%, and leukopenia 2%.	Any event 40%; thrombocytopenia 5%, increased AST 2%, anemia 1%, neutropenia 2%, fatigue 2%, dyspnea 2%, increased ALT 2%.	15% Discontinued, 13% dose reduction	0.6%	[86]
	EMILIA (n = 397)	Any event 94.9%, event-specific rates: nausea 39.2%, fatigue 35.1%, diarrhea 23.3%, thrombocytopenia 28%, elevated AST 22.4%, elevated ALT 16.9%, vomiting 19%, hypokalemia 8.6%, neutropenia 5.9%, mucosal inflammation 6.7%, palmar plantar erythrodysesthesia 1.2%	Thrombocytopenia 12.9%, elevated ALT 4.3%, elevated ALT 2.9%, anemia 2.7%, fatigue 2.4%, hypokalemia 2.2%, neutropenia 2%, diarrhea 1.6%, vomiting 0.8%, nausea 0.8% mucosal inflammation 0.2%	T-Dm was discontinued in 5.9% of patients, mainly due to thrombocytopenia	0. 2%	[56]
T-Dxd	DESTINY-Breast01 (n = 184)	Any adverse event 99.5%, nausea 77.7%, fatigue 49.5%, alopecia 48.4%, vomiting 45.0%, constipation 35.9%, neutropenia 34.8%, decreased appetite 31%, anemia 29.9%, diarrhea 29.3% leukopenia 21.2%, thrombocytopenia 21.2% headache 19.6%, cuff 90%, abdominal pain 16.8%, lymphopenia 14.1%, interstitial lung disease 13.6%, QT prolongation 4.9%, infusion related reaction 2.2%, decreased EF 1.6%	Any adverse event 52.2%, neutropenia 20.7%, anemia 8.7% nausea 7.6%, fatigue 6.0%, vomiting 4.3%, leukopenia 6.0%, thrombocytopenia 3.8%, lymphopenia 6.0%, decreased appetite 1.6%, interstitial lung disease 2.7%, QT prolongation 1.1%, decreased LVEF 0.5%, alopecia 0.5%	Any event 15.2%, dose reduction 23.4%, pneumonitis 5.9%, interstitial lung disease 2.7%	0.21%	[24]
	DESTINY-Breast03 (n = 261)	Any event 99.5%, nausea 73%, fatigue 47.7%, alopecia 37.7%, vomiting 34%, neutropenia 33.2%, anemia 33.2%, increased LFTs 23.5%, thrombocytopenia 23.7%, leukopenia 23.2%, diarrhea 22.4%, constipation 21.3%, decreased appetite 20.6%, pneumonitis 12.1%	Any event 52.6%; neutropenia 13.7%, pneumonitis anemia 8.1%, thrombocytopenia 5.1%, fatigue 7.5%, leukopenia 6.5%, decreased appetite 2.4%, increased LFTs 3.2%, nausea 4.6%, vomiting 1.3%, pneumonitis 2.1%, diarrhea 1.1%	Not reported	0.8%	[7]
	DESTINY-Lung01 (n = 91)	Any adverse event 97%, nausea 73%, fatigue 53%, alopecia 46%, vomiting 40%, neutropenia 35%, anemia 33%, diarrhea 33%, decreased appetite 30%, interstitial lung disease 26%, leukopenia 23%, constipation 20%.	Any adverse event 46%, neutropenia 18%, any adverse event 46%, anemia 10%, nausea 9%, fatigue 7%, leukopenia 4%, vomiting 3%, diarrhea 3%	Dose reduction 34%, dose interruption 32%, %, treatment discontinuation 25%, pneumonitis 13%, interstitial lung disease 5%	2.91%	[5]
Enfortumab vedotin (Padcev) or EV	EV-301 (n = 296)	Any adverse event 93.9%, skin reactions 47%, peripheral neuropathy 46.3%, alopecia 45.3%, peripheral sensory neuropathy 33.8%, pruritus 32.1%, fatigue 31.1%, decreased appetite 30.7%, diarrhea 24.3% dysgeusia 24.3%, nausea 22.6%, anemia 11.5% decrease neutrophil count 10.1%, dry eye 15.9%, infusion related reactions 8.8%neutropenia 6.8%, hyperglycemia 6.4%, decreased leukocyte count 5.4%, febrile neutropenia 0.7%	Any adverse event 51.4%, maculopapular rash 7.4%, fatigue 6.4%, decreased neutrophil count 6.1%, neutropenia 4.7%, diarrhea 3.4%, peripheral sensory neuropathy 3.0%, pruritus 1.4%, decreased white cell count 1.4%, anemia 2.7%, decreased appetite 3%, nausea 1%, febrile neutropenia 0.7%	Dose interruption 51%, dose reduction 32.4%, peripheral sensory neuropathy 15.5%, fatigue 5.4%, decreased neutrophil count 5.1%, rash 3.4%, peripheral neuropathy 3%, anemia 2.7%, drug eruption 2.4% neutropenia 2%, diarrhea 2%, asthenia 2% increased ALT 2%	0.3%	[23]
Sacistuzuzmab Govitecan (SG)	ASCENT trial (n = 235)	Any adverse event 98%, neutropenia 63%, diarrhea 59%, nausea 57%, fatigue 45%, alopecia 46%, anemia 34%, vomiting 29%, nervous system disorders 25%, decreased appetite 20%, constipation 17%, leukopenia 16%, abdominal pain 11%, asthenia 12%, thrombocytopenia 5%, febrile neutropenia 6%	Any adverse event 64%, neutropenia 51%, leukopenia 10%, thrombocytopenia 2%, febrile neutropenia 6%, diarrhea 10%, nausea 3%, vomiting 3%, abdominal pain 1%, fatigue 3%, asthenia 1%	Dose reductions 22%, discontinuation 5%,	1.27%	[25]
Tisotumab vedotin (Tivdak) or TV	innovaTV 204 (n = 101)	Any adverse event 92%, ocular treatment-related events 53% (conjunctivitis 26%, dry eye 23%, keratitis 11%), bleeding 39% (epistaxis 20%, vaginal hemorrhage 7%, hematuria 3%), peripheral neuropathy 33%, alopecia 38%, nausea 27%, fatigue 26%, myalgia 15%, anemia 13%, asthenia 12%, arthralgia 2%, decreased appetite 11%, pruritus 10%, constipation 9%	Any adverse event 28%, neutropenia 3%, fatigue 2%, ulcerative keratitis 2%, peripheral neuropathy 2%, bleeding 2%	Dose interruption 24%, dose reduction 22%, treatment discontinuation 12%, serious adverse events 31%, peripheral neuropathy 2%, pyrexia 2%	0.9%	[27]
Mirvetuximab soravtansine	FDA approval notice and phase I safety study (n = 64)	Diarrhea 43.5%, blurry vision 41.3%, nausea 37%, fatigue 30%, neuropathy 28.3%, keratopathy 26%, AST increased 23.9%, ALT increased 15.2%, vomiting 21.7%, dry 30%, anemia 30%, headache 10.9%, hypokalemia 10.9%, hypomagnesemia 10.9%	Any adverse event 26%, fatigue 4%, hypotension 4%, febrile neutropenia and septic shock 1/64,	Serious adverse events 22%	0	[66]