Safety Data

ENHERTU has serious Warnings and Precautions. Please click here for full Prescribing Information, including Boxed WARNING, and click here for Medication Guide.

ENHERTU safety evaluated in a pooled analysis1

The majority of adverse reactions were Grade 1 or 21

The safety of ENHERTU has been evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2+ breast cancer who received at least one dose of ENHERTU 5.4 mg/kg in Phase 2 DESTINY-Breast01 and Phase 1 Study DS8201-A-J1011

  • Median duration of treatment was 7 months (range: 0.7 to 31)1
  • 94% of patients had visceral disease1
  • 31% of patients had bone metastases1
  • 13% of patients had brain metastases1
  • In the clinical trials, prophylactic or supportive treatment of ENHERTU-induced adverse events was not mandated and was per investigator's discretion and institutional guidelines4
  • Incidence of alopecia in DESTINY-Breast01 Phase 2 study: Grade 1 (36.4%) and Grade 2 (10.9%)4

Common adverse reactions (≥10% all Grades or ≥2% Grades 3 or 4)1

Adverse Reactions
ENHERTU 5.4 mg/kg (N=234)
All Grades
(%)
Grade 3 or 4
(%)
Gastrointestinal Disorders
Nausea
Vomiting
Constipation
Diarrhea
Abdominal paina
Stomatitisb
Dyspepsia
79
47
35
29
19
14
12
7
3.8
0.9
1.7
1.3
0.9
0
General Disorders and Administration Site Conditions Fatiguec 59 6
Skin and Subcutaneous Tissue Disorders
Alopecia
Rashe
46
10
0.4d
0
Metabolism and Nutrition Disorders
Decreased appetite
Hypokalemia
32
12
1.3
3.4
Blood and Lymphatic System Disorders
Anemiaf
Neutropeniag
Leukopeniah
Thrombocytopeniai
31
29
22
20
7
16
6
3.4
Respiratory, Thoracic, and Mediastinal Disorders
Cough
Dyspnea
Epistaxis
Interstitial lung diseasej
20
13
13
9
0
1.3
0
2.6k
Nervous System Disorders
Headachel
Dizziness
19
10
0
0
Infections and Infestation Upper respiratory tract infectionm 15 0
Investigations
Asparatate aminotransferase increased
Alanine aminotransferase increased
14
10
0.9
0.9
Eye Disorders
Dry eye
11 0.4n
Adverse
Reactions
ENHERTU
5.4 mg/kg
(N=234)
All
Grades
(%)
Grade
3 or 4
(%)
Gastrointestinal Disorders Nausea 79 7
Vomiting 47 3.8
Constipation 35 0.9
Diarrhea 29 1.7
Abdominal
paina
19 1.3
Stomatitisb 14 0.9
Dyspepsia 12 0
General Disorders and
Administration Site Conditions
Fatiguec 59 6
Skin and Subcutaneous
Tissue Disorders
Alopecia 46 0.4d
Rashe 10 0
Metabolism and
Nutrition Disorders
Decreased appetite 32 1.3
Hypokalemia 12 3.4
Blood and Lymphatic
System Disorders
Anemiaf 31 7
Neutropeniag 29 16
Leukopeniah 22 16
Thrombocytopeniai 20 3.4
Respiratory, Thoracic, and
Mediastinal Disorders
Cough 20 0
Dyspnea 13 1.3
Epistaxis 13 0
Interstitial lung diseasej 9 2.6k
Nervous System
Disorders
Headachel 19 0
Dizziness 10 0
Infections and
Infestation
Upper
respiratory
tract
infectionm
15 0
Investigations Asparatate aminotrans-ferase increased 14 0.9
Alanine aminotransferase increased 10 0.9
Eye
Disorders
Dry eye 11 0.4n

Events were graded using NCI-CTCAE version 4.03. N=number of patients exposed; PT=preferred term. Percentages were calculated using the number of patients in the Safety Analysis Set as the denominator.

a Grouped term of abdominal pain includes PTs of abdominal discomfort, gastrointestinal pain, abdominal pain, abdominal pain lower, and abdominal pain upper.

b Grouped term of stomatitis includes PTs of stomatitis, aphthous ulcer, mouth ulceration, oral mucosa erosion, and oral mucosa blistering. One Grade 1 event of aphthous ulcer was not included in the summary of grouped term stomatitis (from DESTINY-Breast01).

c Grouped term of fatigue includes PTs of fatigue and asthenia.

d This Grade 3 event was reported by the investigator. Per NCI-CTCAE v.4.03, the highest NCI-CTCAE grade for alopecia is Grade 2.

e Grouped term of rash includes PTs of rash, rash pustular, rash maculo-papular.

f Grouped term of anemia includes PTs of anemia, hemoglobin decreased, hematocrit decreased, and red blood cell count decreased.

g Grouped term of neutropenia includes PTs of neutropenia and neutrophil count decreased.

h Grouped term of leukopenia includes PTs of leukopenia, lymphopenia, and white blood cell count decreased.

i Grouped term of thrombocytopenia includes PTs of thrombocytopenia and platelet count decreased.

jInterstitial lung disease includes events that were adjudicated as ILD: pneumonitis, interstitial lung disease, respiratory failure, organizing pneumonia, acute respiratory failure, lung infiltration, lymphangitis, alveolitis.

k All events had fatal outcomes (n=6).

l Grouped term of headache includes PTs of headache, sinus headache, and migraine.

m Grouped term of upper respiratory tract infection includes PTs of influenza, influenza-like illness, upper respiratory tract infection.

n This Grade 4 event was reported by the investigator. Per NCI-CTCAE v.4.03, the highest NCI-CTCAE grade for dry eye is Grade 3.

Other adverse reactions in pooled analysis of patients treated with ENHERTU (N=234)1

Other clinically relevant adverse reactions reported in <10% of patients were:
  • Injury, Poisoning and Procedural Complications: infusion-related reactions (2.6%)
  • Blood and Lymphatic System Disorders: febrile neutropenia (1.7%)

Serious adverse reactions occurred in 20% of patients receiving ENHERTU.

Serious adverse reactions in >1% of patients included:
  • Interstitial lung disease
  • Pneumonia
  • Vomiting
  • Nausea
  • Cellulitis
  • Hypokalemia
  • Intestinal obstruction
Fatalities due to adverse reactions occurred in 4.3% of patients:
  • Interstitial lung disease (2.6%)
  • Acute hepatic failure/acute kidney injury (0.4%)
  • General physical health deterioration (0.4%)
  • Pneumonia (0.4%)
  • Hemorrhagic shock (0.4%)
9%Discontinuation
Due to Adverse Reactions
  • The most frequent adverse reaction associated with permanent discontinuation was ILD (6%)
  • Permanently discontinue ENHERTU in patients who are diagnosed with any symptomatic (Grade 2 or greater) ILD
33%
Dose Interruptions
Due to Adverse Reactions
  • The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, thrombocytopenia, leukopenia, upper respiratory tract infection, fatigue, nausea, and ILD
18%
Dose Reductions
Due to Adverse Reactions
  • The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, and neutropenia
Most common adverse reactions (frequency ≥20%)
  • Nausea (79%)
  • Fatigue (59%)
  • Vomiting (47%)
  • Alopecia (46%)
  • Constipation (35%)
  • Decreased appetite (32%)
  • Anemia (31%)
  • Neutropenia (29%)
  • Diarrhea (29%)
  • Leukopenia (22%)
  • Cough (20%)
  • Thrombocytopenia (20%)

Selected laboratory abnormalities worsened from baseline reported in patients with HER2+ unresectable or metastatic breast cancer in a pooled analysis of patients treated with ENHERTU1

Laboratory Parameter
ENHERTU 5.4 mg/kg (N=234)
All Grades (%) Grade 3 or 4
(%)
Hematology
White blood cell count decreased
Hemoglobin decreased
Neutrophil count decreased
Platelet count decreased
70 7
70 7
62 16
37 3.4
Chemistry
Aspartate aminotransferase increased
Alanine aminotransferase increased
Hypokalemia
41 0.9
38 0.4
26 3.0
Laboratory
Parameter
ENHERTU
5.4 mg/kg
(N=234)
All
Grades
(%)
Grade
3 or 4
(%)
Hematology White blood cell count decreased 70 7
Hemoglobin decreased 70 7
Neutrophil count decreased 62 16
Platelet count decreased 37 3.4
Chemistry Aspartate aminotransferase
increased
41 0.9
Alanine aminotransferase increased 38 0.4
Hypokalemia 26 3.0
Percentages were calculated using patients with worsening laboratory values from baseline and the number of patients with both baseline and post-treatment measurements as the denominator. Frequencies were based on NCI-CTCAE v.4.03 grade-derived laboratory abnormalities.

Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU; monitor patients and initiate management at first sign of ILD1*

Learn more about the management of potential risks of treatment, including ILD, neutropenia, and left ventricular ejection fraction decrease.

*ILD includes events that were adjudicated as ILD: pneumonitis, interstitial lung disease, respiratory failure, organizing pneumonia, acute respiratory failure, lung infiltration, lymphangitis, alveolitis.1

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