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 HER2-Positive 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 HER2-Low Metastatic Breast Cancer
ENHERTU is indicated for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy [see Dosage and Administration (2.1)].
1.3 Unresectable or Metastatic HER2-Mutant Non-Small Cell Lung Cancer
ENHERTU is indicated for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy.
This indication is approved under accelerated approval based on objective response rate and duration of response [see Clinical Studies (14.3)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
1.4 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
Unresectable or Metastatic HER2-Low Breast Cancer
Select patients for treatment of unresectable or metastatic HER2-low breast cancer with ENHERTU based on HER2 expression (IHC 1+ or IHC 2+/ISH-) [see Clinical Studies (14.2)].
Unresectable or Metastatic HER2-Mutant NSCLC
Select patients for the treatment of unresectable or metastatic HER2-mutant NSCLC with ENHERTU based on the presence of activating HER2 (ERBB2) mutations in tumor or plasma specimens [see Clinical Studies (14.3)]. If no mutation is detected in a plasma specimen, test tumor tissue.
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.
Additional Patient Selection Information
Information on FDA-approved tests for the detection of HER2 protein expression, HER2 gene amplification, and activating HER2 mutations 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.
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 Unresectable or Metastatic HER2-Mutant NSCLC
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 Dosage 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.
Dose Reduction Schedule | Breast Cancer and NSCLC | 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. |
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 [see Warnings and Precautions (5.1)] | Asymptomatic ILD/pneumonitis(Grade 1) | Interrupt ENHERTU until resolved to Grade 0, then:
| |
Symptomatic ILD/pneumonitis(Grade 2 or greater) |
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Neutropenia [see Warnings and Precautions (5.2)] | Grade 3 (less than 1.0 to 0.5 × 109 /L) |
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Grade 4 (less than 0.5 × 109 /L) |
| ||
Febrile Neutropenia [see Warnings and Precautions (5.2)] | 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 |
| |
Thrombocytopenia[see Adverse Reactions (6.1)] | Grade 3 (platelets less than 50 to 25 × 109 /L) |
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Grade 4 (platelets less than 25 × 109 /L) |
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Left Ventricular Dysfunction [see Warnings and Precautions (5.3)] | LVEF greater than 45% and absolute decrease from baseline is 10% to 20% |
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LVEF 40% to 45% | And absolute decrease from baseline is less than 10% |
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And absolute decrease from baseline is 10% to 20% |
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LVEF less than 40% or absolute decrease from baseline is greater than 20% |
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Symptomatic congestive heart failure (CHF) |
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