Management of Potential Risks
of Treatment

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)

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

  • 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)

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

*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.

HER2, human epidermal growth factor receptor 2.

Patient Resources:

    Understanding and Managing Side Effects During Treatment With ENHERTU

  • Understanding and Managing Side Effects During Treatment With ENHERTU

It could be more than a cough

Identification of the signs and symptoms of ILD, including cough, dyspnea, fever, and worsening respiratory symptoms, can help inform patient management.1

ILD identification1,2

Severity Description (NCI-CTCAEa grading)
Grade 1 Asymptomatic, clinical or diagnostic observations only
Grade 2 Symptomatic, limiting instrumental activities of daily living
Grade 3 Severe symptoms, limiting self-care activities of daily living; oxygen indicated
Grade 4 Life-threatening respiratory compromise
Grade 5 Death
a Toxicity grades are in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v.4.03).

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

Potential questions to ask your patients to help early identification of ILD3,4

  • Have you been coughing recently? Is it a dry cough?
  • Have you had any shortness of breath, especially during or after physical activity?
  • Have you experienced any new breathing or respiratory problems?
  • If you already have respiratory problems, have they gotten worse?
  • Have you had a fever?
  • Have you been feeling tired?
  • Have you lost weight?

Patient counseling regarding ILD1

  • Advise patients to read the FDA-approved patient labeling: download the Medication Guide
  • Inform patients of the risks of severe or fatal ILD
  • Advise patients to contact their healthcare provider immediately for any of the following: cough, shortness of breath, fever, or other new or worsening respiratory symptoms

Patient counseling regarding ILD1

  • Advise patients to read the FDA-approved patient labeling: download the Medication Guide
  • Inform patients of the risks of severe or fatal ILD
  • Advise patients to contact their healthcare provider immediately for any of the following: cough, shortness of breath, fever, or other new or worsening respiratory symptoms
  • Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated
  • Based on the severity of neutropenia, manage through treatment interruption or dose reduction
  • Of the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 29.5% of patients and 16.2% had Grade 3 or 4 events. Febrile neutropenia was reported in 1.7% of patients

Dose modifications for neutropenia1

Severity Treatment Modification
Grade 3
(ANC less than 1.0 to 0.5 x 109/L)
  • Interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose
Grade 4
(ANC less than 0.5 x 109/L)

Toxicity grades are in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v.4.03).

Dose modifications for febrile neutropenia1

Severity Treatment Modification
Absolute neutrophil count of less than 1.0 x 109/L and temperature is greater than 38.3℃ or a sustained temperature of ≥38℃ for more than one hour
Toxicity grades are in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v.4.03).
ANC, absolute neutrophil count.
  • Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated
  • Manage through treatment interruption or discontinuation
  • LVEF decrease has been observed with anti-HER2 therapies. In the 234 patients with unresectable or metastatic HER2+ breast cancer who received ENHERTU 5.4 mg/kg, two cases (0.9%) of asymptomatic LVEF decrease were reported. No decreases of LVEF to <40% were observed

Dose modifications for decreased LVEF1

Severity Treatment Modification
LVEF greater than 45% and absolute decrease from baseline is 10% to 20%
  • Continue treatment with ENHERTU
LVEF
40%
to 45%
And absolute decrease from baseline is less than 10%
And absolute decrease from baseline is 10% to 20%
  • Continue treatment with ENHERTU
  • Repeat LVEF assessment within 3 weeks
  • Interrupt ENHERTU
  • Repeat LVEF assessment within 3 weeks
  • If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU
  • If LVEF recovers to within 10% of baseline, resume treatment with ENHERTU at the same dose
LVEF less than 40% or absolute decrease from baseline is greater than 20%
  • Interrupt ENHERTU
  • Repeat LVEF assessment within 3 weeks
  • If LVEF of less than 40% or absolute decrease from baseline of greater than 20% is confirmed, permanently discontinue ENHERTU
Symptomatic congestive heart failure (CHF)
  • Permanently discontinue ENHERTU
Toxicity grades are in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v.4.03).

Nausea toxicity grading criteria1,2

Severity Description (NCI-CTCAEb grading) Incidence in
DESTINY-Breast01
with ENHERTU 5.4 mg/kg
(N=184)
Grade 1 and Grade 2
  • Grade 1: Loss of appetite without alteration in eating habits
  • Grade 2: Oral intake decreased without significant weight loss, dehydration or malnutrition
72%
Grade 3 and Grade 4
  • Grade 3: Inadequate oral caloric or fluid intake; tube feeding, TPN, or hospitalization indicated
  • Grade 4: Not available
7%
b National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) version 4.03.
TPN, total parenteral nutrition.

Vomiting toxicity grading criteria1,2

Severity Description (NCI-CTCAEb grading) Incidence in
DESTINY-Breast01
with ENHERTU 5.4 mg/kg
(N=184)
Grade 1 and Grade 2
  • Grade 1: 1-2 episodes (separated by 5 minutes) in 24 hours
  • Grade 2: 3-5 episodes (separated by 5 minutes) in 24 hours
43.2%
Grade 3 and Grade 4
  • Grade 3: ≥6 episodes (separated by 5 minutes) in 24 hours; tube feeding, TPN or hospitalization indicated
  • Grade 4: Life-threatening consequences
3.8%

Fatigue toxicity grading criteria1,2

Severity Description (NCI-CTCAEb grading) Incidence in DESTINY-Breast01
with ENHERTU 5.4 mg/kg
(N=184)
Grade 1 and Grade 2
  • Grade 1: Fatigue relieved by rest
  • Grade 2: Fatigue not relieved by rest, limiting instrumental activities of daily living
43%
Grade 3 and Grade 4
  • Grade 3: Fatigue not relieved by rest, limiting self-care activities of daily living
  • Grade 4: Not available
5%

Alopecia toxicity grading criteria1,2

Severity Description (NCI-CTCAEb grading) Incidence in DESTINY-Breast01
with ENHERTU 5.4 mg/kg
(N=184)
Grade 1 and Grade 2
  • 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
36.4%
  • Grade 2: Hair loss of ≥50% of normal 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
10.9%
* 0.4% grade 3 alopecia was reported by investigators. Per NCI-CTCAE v.4.03, the highest NCI-CTCAE grade for alopecia was Grade 2.1,3
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