ENHERTU Efficacy and Safety

ENHERTU efficacy data

In heavily pretreated patients with HER2+ unresectable or mBC,a

ENHERTU monotherapy demonstrated a 60.3% confirmed ORR1,b
efficiency efficiency
ENHERTU demonstrated a durable mDOR of nearly 15 months1,c
efficiency efficiency

aPatients had received a median of 5 (range: 2-17) prior cancer regimens in the locally advanced/metastatic setting.1

bORR, defined as CR+PR per RECIST v1.1 in the intention to treat population as evaluated by independent central review. ORR 95% CI calculated using Clopper-Pearson method.1

cDOR based on a median duration of follow-up of 11.1 months. Median DOR based on Kaplan-Meier estimate. 95% CI calculated using Brookmeyer-Crowley method.1

dData based on cut-off date of August 1, 2019.2

ePatients with inactive (asymptomatic and previously treated) brain metastases. Brain lesions were non-target lesions.

CI, confidence interval; CR, complete response; HER2, human epidermal growth factor receptor 2; HR, hormone receptor; ICR, independent central review; ITT, intent to treat; mBC, metastatic breast cancer; mDOR, median duration of response; ORR, objective response rate; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors.

Learn more about ENHERTU dosing and administration

ENHERTU safety data

 

ENHERTU has serious Warning 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 safety of ENHERTU has been evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg in DESTINY-Breast01 and 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
  • The majority of adverse reactions were Grade 1 or 21
  • In the clinical trials, prophylactic or supportive treatment of ENHERTU induced adverse events was not mandated and was per investigator's discretion and institutional guidelines2
Common adverse reactions (≥10% all Grades or ≥2% Grades 3 or 4)1
Adverse Reactions
ENHERTU 5.4 mg/kg (N=234)
All Grades (0%) 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 Disorder and Administration Site Condition Fatiguec 59 6
Skin and Subcutaneous Tissues Disorders
Alopecia
Rashe
46
04d
10
0
Metabolism and Nutrition Disorders
Decreased Appetite
Hypokalemia
32
12
1.3
3.4
Blood and Lymphatic System Disorders
Anamiaf
Neutropeniag
Leukopeniah
Thrombocytopeniai
31
29
22
20
7
16
6
3.4
Respiratory,Thoracic and Mediastinal Disorders
Cough
Dyspnea
Epistaxis
Intertitial lung diseasej
20
13
13
9
0
1.3
0
2.6k
Nervous System Disorders
Headachel
Dizziness
19
10
0
0
Infection and Infestation
Upper respiratory tract infectionm
15 0
Investigations
Asparatate aminotransferase increased
Alanine aminotransferase increased
14
10
0.9
0.9
Eye Disorder
Dry Eye
11 0.4n
  • Incidence of alopecia in DESTINY-Breast01 Phase 2 study: Grade 1 (36.4%) and Grade 2 (10.9%)2

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 clinically relevant adverse reactions reported in <10% of patients were1:

  • Injury, Poisoning and Procedural Complications: infusion-related reactions (2.6%)
  • Blood and Lymphatic System Disorders: febrile neutropenia (1.7%)
 
Most common adverse events in a pooled analysis of patients treated with ENHERTU (N=234)1

Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were interstitial lung disease, pneumonia, vomiting, nausea, cellulitis, hypokalemia, and intestinal obstruction. Fatalities due to adverse reactions occurred in 4.3% of patients including interstitial lung disease (2.6%), and the following events occurred in one patient each (0.4%): acute hepatic failure/acute kidney injury, general physical health deterioration, pneumonia, and hemorrhagic shock.

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 reductions were fatigue, nausea, and neutropenia
9%
Discontinuation
Due to Adverse Reactions
  • The most frequent adverse reactions associated with permanent discontinuation was ILD(6%)
  • Permanent discontinue ENHERTU in patients who are diagnosed with any any symptomatic (Grade 2 or greater) ILD
  • The most common adverse reactions (frequency ≥20%) were nausea (79%), fatigue (59%), vomiting (47%), alopecia (46%), constipation (35%), decreased appetite (32%), anemia (31%), neutropenia (29%), diarrhea (29%), leukopenia (22%), cough (20%), and 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 (0%) 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
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
  • Severe, life threatening, or fatal ILD, including pneumonitis can occur in patients treated with ENHERTU
  • In clinical studies, of the 234 patients with HER2+ unresectable or mBC treated with ENHERTU, ILD occurred in 9% of patients
  • Fatal outcomes due to ILD and/or pneumonitis occurred in 2.6% of patients
  • Median time to first onset was 4.1 months (range: 1.2 to 8.3)
  • Severe, life threatening, or fatal ILD, including pneumonitis can occur in patients treated with ENHERTU
  • In clinical studies, of the 234 patients with HER2+ unresectable or mBC treated with ENHERTU, ILD occurred in 9% of patients
  • Fatal outcomes due to ILD and/or pneumonitis occurred in 2.6% of patients
  • Median time to first onset was 4.1 months (range: 1.2 to 8.3)

Patient counseling regarding ILD

  • Advise patients to read the FDA-approved patient labeling (Medication Guide)
  • Inform patients of the risks of severe, life threatening or fatal ILD
  • Advise patients to contact their healthcare provider immediately for any of the following: cough, dyspnea, fever, and/or any new or worsening respiratory symptoms

Patient counseling regarding ILD

  • Advise patients to read the FDA-approved patient labeling (Medication Guide)
  • Inform patients of the risks of severe, life threatening or fatal ILD
  • Advise patients to contact their healthcare provider immediately for any of the following: cough, dyspnea, fever, and/or any new or worsening respiratory symptoms

Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms

Monitor patients for signs and symptoms of ILD/pneumonitis: interrupt ENHERTU and initiate corticosteroid treatment if ILD is suspected1

Promptly investigate evidence of ILD

  • Evaluate patients with suspected ILD by radiographic imaging
  • Consider consultation with a pulmonologist

For asymptomatic ILD (Grade 1)

  • Consider corticosteroid treatment (e.g., ≥0.5 mg/kg prednisolone or equivalent)
  • Interrupt ENHERTU until resolved to Grade 0, then:

For symptomatic ILD (Grade 2 or greater)

  • Promptly initiate corticosteroid treatment (e.g., ≥1 mg/kg prednisolone or equivalent)
  • Upon improvement, follow by gradual taper (e.g., 4 weeks)
  • Permanently discontinue ENHERTU in patients who are diagnosed with any symptomatic ILD
*Interstitial lung disease includes events that were adjudicated as ILD: pneumonitis, interstitial lung disease, respiratory failure, organizing pneumonia, acute respiratory failure, lung infiltration, lymphangitis, alveolitis.

Learn more about the Management of Potential Risks of Treatment

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