Enhertu

ENHERTU- trastuzumab deruxtecan injection, powder, lyophilized, for solution
Daiichi Sankyo, Inc.

WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

  • Interstitial Lung Disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and the need to immediately report symptoms [see Dosage and Administration (2.3), Warnings and Precautions (5.1)].
  • Embryo-Fetal Toxicity: Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception [see Warnings and Precautions (5.4), Use in Specific Populations (8.1, 8.3)].

1 INDICATIONS AND USAGE

1.1 Metastatic Breast Cancer

ENHERTU is indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either:

  • in the metastatic setting, or
  • in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy.

1.2 Locally Advanced or Metastatic Gastric Cancer

ENHERTU is indicated for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.

2 DOSAGE AND ADMINISTRATION

2.1 Patient Selection for Locally Advanced or Metastatic Gastric Cancer

Select patients with locally advanced or metastatic gastric cancer based on HER2 protein overexpression or HER2 gene amplification. Reassess HER2 status if it is feasible to obtain a new tumor specimen after prior trastuzumab-based therapy and before treatment with ENHERTU.

Information on FDA-approved tests for the detection of HER2 protein overexpression and HER2 gene amplification in gastric cancer is available at: http://www.fda.gov/CompanionDiagnostics.

2.2 Recommended Dosage and Schedules

Do not substitute ENHERTU for or with trastuzumab or ado-trastuzumab emtansine.

First infusion: Administer infusion over 90 minutes.

Subsequent infusions: Administer over 30 minutes if prior infusions were well tolerated.

Slow or interrupt the infusion rate if the patient develops infusion-related symptoms.

Permanently discontinue ENHERTU in case of severe infusion reactions.

Premedication

ENHERTU is moderately emetogenic [see Adverse Reactions (6.1)] , which includes delayed nausea and/or vomiting. Administer prophylactic antiemetic medications per local institutional guidelines for prevention of chemotherapy-induced nausea and vomiting.

Recommended Dosage for Metastatic Breast Cancer

The recommended dosage of ENHERTU is 5.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.

Recommended Dosage for Locally Advanced or Metastatic Gastric Cancer

The recommended dosage of ENHERTU is 6.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.

2.3 Dose Modifications

Management of adverse reactions may require temporary interruption, dose reduction, or treatment discontinuation of ENHERTU as described in Tables 1 and 2.

Do not re-escalate the ENHERTU dose after a dose reduction is made.

If a planned dose is delayed or missed, administer as soon as possible; do not wait until the next planned cycle. Adjust the schedule of administration to maintain a 3-week interval between doses. Administer the infusion at the dose and rate the patient tolerated in the most recent infusion.

Table 1: Dose Reduction Schedule
Dose Reduction Schedule Breast Cancer Gastric Cancer
Recommended starting dose 5.4 mg/kg 6.4 mg/kg
First dose reduction 4.4 mg/kg 5.4 mg/kg
Second dose reduction 3.2 mg/kg 4.4 mg/kg
Requirement for further dose reduction Discontinue treatment. Discontinue treatment.
Table 2: Dose Modifications for Adverse Reactions
Adverse Reaction Severity Treatment Modification
Toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v.5.0).
Interstitial Lung Disease (ILD)/ Pneumonitis Asymptomatic ILD/pneumonitis (Grade 1) Interrupt ENHERTU until resolved to Grade 0, then:
  • if resolved in 28 days or less from date of onset, maintain dose.
  • if resolved in greater than 28 days from date of onset, reduce dose one level (see Table 1).
  • consider corticosteroid treatment as soon as ILD/pneumonitis is suspected [see Warnings and Precautions (5.1)].
Symptomatic ILD/pneumonitis (Grade 2 or greater)
  • Permanently discontinue ENHERTU.
  • Promptly initiate corticosteroid treatment as soon as ILD/pneumonitis is suspected [see Warnings and Precautions (5.1)].
Neutropenia Grade 3 (less than 1.0 to 0.5 × 109 /L)
  • Interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose.
Grade 4 (less than 0.5 × 109 /L)
  • Interrupt ENHERTU until resolved to Grade 2 or less.
  • Reduce dose by one level (see Table 1).
Febrile Neutropenia Absolute neutrophil count of less than 1.0 × 109 /L and temperature greater than 38.3°C or a sustained temperature of 38°C or greater for more than one hour
  • Interrupt ENHERTU until resolved.
  • Reduce dose by one level (see Table 1).
Thrombocytopenia Grade 3 (platelets less than 50 to 25 × 109 /L)
  • Interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose.
Grade 4 (platelets less than 25 × 109 /L)
  • Interrupt ENHERTU until resolved to Grade 1 or less.
  • Reduce dose by one level (see Table 1).
Left Ventricular Dysfunction 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%
  • Continue treatment with ENHERTU.
  • Repeat LVEF assessment within 3 weeks.
And absolute decrease from baseline is 10% to 20%
  • 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% from 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.

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