Other Select Adverse Reactions

Grade, description, and incidence of select ARs observed with ENHERTU and T-DM1

The majority of these ARs were Grade 1 or 2. Events were graded using NCI-CTCAE v.5.0.1

Nausea toxicity grading criteria1,2

Severity Description (NCI-CTCAE grading) Incidence in DESTINY-Breast03 (%)
ENHERTU
5.4 mg/kg (n=257)
T-DM1
3.6 mg/kg (n=261)
Grades 1 and 2
  • Grade 1: Loss of appetite without alteration in eating habits
  • Grade 2: Oral intake decreased without significant weight loss, dehydration, or malnutrition
69.3 29.9
Grades 3 and 4
  • Grade 3: Inadequate oral caloric or fluid intake; tube feeding, TPN, or hospitalization indicated
  • Grade 4: Not applicable
6.6 0.4
Description
(NCI-CTCAE grading)
Incidence in DESTINY-Breast03 (%)
ENHERTU
5.4 mg/kg (n=257)
T-DM1
3.6 mg/kg (n=261)
Grades 1 and 2
  • Grade 1: Loss of appetite without alteration in eating habits
  • Grade 2: Oral intake decreased without significant weight loss, dehydration, or malnutrition
69.3 29.9
Grades 3 and 4
  • Grade 3: Inadequate oral caloric or fluid intake; tube feeding, TPN, or hospitalization indicated
  • Grade 4: Not applicable
6.6 0.4
  • Premedication: ENHERTU is moderately emetogenic, which includes delayed nausea and/or vomiting. Administer prophylactic antiemetic medications per local institutional guidelines for prevention of chemotherapy-induced nausea and vomiting3

Fatigue toxicity grading criteria1,2

Severity Description (NCI-CTCAE grading) Incidence in DESTINY-Breast03 (%)
ENHERTU
5.4 mg/kg (n=257)
T-DM1
3.6 mg/kg (n=261)
Grades 1 and 2
  • Grade 1: Fatigue relieved by rest
  • Grade 2: Fatigue not relieved by rest; limiting instrumental activities of daily living
43.2 33.7
Grades 3 and 4
  • Grade 3: Fatigue not relieved by rest, limiting self-care activities of daily living
  • Grade 4: Not applicable
5.8 0.8
Description (NCI-CTCAE grading) Incidence in DESTINY-Breast03 (%)
ENHERTU
5.4 mg/kg (n=257)
T-DM1
3.6 mg/kg (n=261)
Grades 1 and 2
  • Grade 1: Fatigue relieved by rest
  • Grade 2: Fatigue not relieved by rest; limiting instrumental activities of daily living
43.2 33.7
Grades 3 and 4
  • Grade 3: Fatigue not relieved by rest, limiting self-care activities of daily living
  • Grade 4: Not applicable
5.8 0.8

Alopecia toxicity grading criteria2-4,a

Severity Description (NCI-CTCAE grading) Incidence in DESTINY-Breast03 (%)
ENHERTU
5.4 mg/kg (n=257)
T-DM1
3.6 mg/kg (n=261)
Grade 1
  • Grade 1: Hair loss of <50% of normal for that individual that is not obvious from a distance but only on close inspection; a different hair style may be required to cover the hair loss but it does not require a wig or hair piece to camouflage
26.5 2.3
Grade 2
  • Grade 2: Hair loss of ≥50% of normal for that individual that is readily apparent to others; a wig or hair piece is necessary if the patient desires to completely camouflage the hair loss; associated with psychosocial impact
9.3 0
Description (NCI-CTCAE grading) Incidence in DESTINY-Breast03 (%)
ENHERTU
5.4 mg/kg (n=257)
T-DM1
3.6 mg/kg (n=261)
Grade 1
  • Grade 1: Hair loss of <50% of normal for that individual that is not obvious from a distance but only on close inspection; a different hair style may be required to cover the hair loss but it does not require a wig or hair piece to camouflage
26.5 2.3
Grade 2
  • Grade 2: Hair loss of ≥50% of normal for that individual that is readily apparent to others; a wig or hair piece is necessary if the patient desires to completely camouflage the hair loss; associated with psychosocial impact
9.3 0

aOne Grade 3 event was reported by an investigator. Per NCI-CTCAE v.5.0, the highest NCI-CTCAE grade for alopecia is Grade 2.

Vomiting toxicity grading criteria1,2

Severity Description (NCI-CTCAE grading) Incidence in DESTINY-Breast03 (%)
ENHERTU
5.4 mg/kg (n=257)
T-DM1
3.6 mg/kg (n=261)
Grades 1 and 2
  • Grade 1: Intervention not indicated
  • Grade 2: Outpatient IV hydration; medical intervention indicated
47.4 9.2
Grades 3 and 4
  • Grade 3: Tube feeding, TPN, or hospitalization indicated
  • Grade 4: Life-threatening consequences
1.6 0.8
Description (NCI-CTCAE grading) Incidence in DESTINY-Breast03 (%)
ENHERTU
5.4 mg/kg (n=257)
T-DM1
3.6 mg/kg (n=261)
Grades 1 and 2
  • Grade 1: Intervention not indicated
  • Grade 2: Outpatient IV hydration; medical intervention indicated
47.4 9.2
Grades 3 and 4
  • Grade 3: Tube feeding, TPN, or hospitalization indicated
  • Grade 4: Life-threatening consequences
1.6 0.8
  • Premedication: ENHERTU is moderately emetogenic, which includes delayed nausea and/or vomiting. Administer prophylactic antiemetic medications per local institutional guidelines for prevention of chemotherapy-induced nausea and vomiting3

Constipation toxicity grading criteria1,2

Severity Description (NCI-CTCAE grading) Incidence in DESTINY-Breast03 (%)
ENHERTU
5.4 mg/kg (n=257)
T-DM1
3.6 mg/kg (n=261)
Grades 1 and 2
  • Grade 1: Occasional or intermittent symptoms; occasional use of stool softeners, laxatives, dietary modification, or enema
  • Grade 2: Persistent symptoms with regular use of laxatives or enemas; limiting instrumental activities of daily living
34.2 19.5
Grades 3 and 4
  • Grade 3: Obstipation with manual evacuation indicated; limiting self-care activities of daily living
  • Grade 4: Life-threatening consequences; urgent intervention indicated
0 0
Description (NCI-CTCAE grading) Incidence in DESTINY-Breast03 (%)
ENHERTU
5.4 mg/kg (n=257)
T-DM1
3.6 mg/kg (n=261)
Grades 1 and 2
  • Grade 1: Occasional or intermittent symptoms; occasional use of stool softeners, laxatives, dietary modification, or enema
  • Grade 2: Persistent symptoms with regular use of laxatives or enemas; limiting instrumental activities of daily living
34.2 19.5
Grades 3 and 4
  • Grade 3: Obstipation with manual evacuation indicated; limiting self-care activities of daily living
  • Grade 4: Life-threatening consequences; urgent intervention indicated
0 0

Decreased appetite toxicity grading criteria1,2

Severity Description (NCI-CTCAE grading) Incidence in DESTINY-Breast03 (%)
ENHERTU
5.4 mg/kg (n=257)
T-DM1
3.6 mg/kg (n=261)
Grades 1 and 2
  • Grade 1: Loss of appetite without alteration in eating habits
  • Grade 2: Oral intake altered without significant weight loss or malnutrition; oral nutritional supplements indicated
27.6 16.5
Grades 3 and 4
  • Grade 3: Associated with significant weight loss or malnutrition (e.g., inadequate oral caloric and/or fluid intake); tube feeding or TPN indicated
  • Grade 4: Life-threatening consequences; urgent intervention indicated
1.6 0.4
Description (NCI-CTCAE grading) Incidence in DESTINY-Breast03 (%)
ENHERTU
5.4 mg/kg (n=257)
T-DM1
3.6 mg/kg (n=261)
Grades 1 and 2
  • Grade 1: Loss of appetite without alteration in eating habits
  • Grade 2: Oral intake altered without significant weight loss or malnutrition; oral nutritional supplements indicated
27.6 16.5
Grades 3 and 4
  • Grade 3: Associated with significant weight loss or malnutrition (e.g., inadequate oral caloric and/or fluid intake); tube feeding or TPN indicated
  • Grade 4: Life-threatening consequences; urgent intervention indicated
1.6 0.4

Diarrhea toxicity grading criteria1,2

Severity Description (NCI-CTCAE grading) Incidence in DESTINY-Breast03 (%)
ENHERTU
5.4 mg/kg (n=257)
T-DM1
3.6 mg/kg (n=261)
Grades 1 and 2
  • Grade 1: Increase of <4 stools per day over baseline; mild increase in ostomy output compared to baseline
  • Grade 2: Increase of 4-6 stools per day over baseline; moderate increase in ostomy output compared to baseline; limiting instrumental activities of daily living
28 6.5
Grades 3 and 4
  • Grade 3: Increase of ≥7 stools per day over baseline; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self-care activities of daily living
  • Grade 4: Life-threatening consequences; urgent intervention indicated
1.2 0.4
Description (NCI-CTCAE grading) Incidence in DESTINY-Breast03 (%)
ENHERTU
5.4 mg/kg (n=257)
T-DM1
3.6 mg/kg (n=261)
Grades 1 and 2
  • Grade 1: Increase of <4 stools per day over baseline; mild increase in ostomy output compared to baseline
  • Grade 2: Increase of 4-6 stools per day over baseline; moderate increase in ostomy output compared to baseline; limiting instrumental activities of daily living
28 6.5
Grades 3 and 4
  • Grade 3: Increase of ≥7 stools per day over baseline; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self-care activities of daily living
  • Grade 4: Life-threatening consequences; urgent intervention indicated
1.2 0.4

Review management information for these other potential treatment risks:

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AR, adverse reaction; IV, intravenous; NCI-CTCAE, National Cancer Institute–Common Terminology Criteria for Adverse Events; T-DM1, ado-trastuzumab emtansine; TPN, total parenteral nutrition.