ENHERTU POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION 100MG/VIAL [SIN16352P]

Product Info

ENHERTU POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION 100MG/VIAL

[SIN16352P]

Indication

4.1 Therapeutic indications

Metastatic Breast Cancer

HER2-Positive

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.

HER2-Low and HER2-Ultralow

ENHERTU as a monotherapy is indicated for the treatment of adult patients with unresectable or metastatic

• Hormone receptor-positive HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer who have received at least one endocrine therapy in the metastatic setting.

• HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received at least one prior line of chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy. Patients with hormone receptor-positive breast cancer should have received at least one and be no longer considered eligible for endocrine therapy.

Unresectable or Metastatic Non-Small Cell Lung Cancer (NSCLC)

ENHERTU is indicated for the treatment of adult patients with unresectable or metastatic NSCLC whose tumors have activating HER2 (ERBB2) mutations and who have received a prior systemic therapy.

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 two or more prior regimens, including a trastuzumab-based regimen.

Other Unresectable or Metastatic Solid Tumors

ENHERTU is indicated as monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who show progression after at least one prior systemic treatment and who have no satisfactory alternative treatment options.

Dosing

4.2 Posology and method of administration

In order to prevent medicinal product errors, it is important to check the vial labels to ensure that the medicinal product being prepared and administered is ENHERTU (trastuzumab deruxtecan) and not trastuzumab or trastuzumab emtansine.

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

Patient Selection for HER2-low or HER2-ultralow Metastatic Breast Cancer

Select patients for treatment of unresectable or metastatic HER2-low breast cancer based on IHC 1+ or IHC 2+/ISH-, or HER2-ultralow breast cancer based on IHC 0 with membrane staining (IHC >0<1+) tumor status detected by a validated test.

Patient Selection for Unresectable or Metastatic NSCLC

Select patients for the treatment of unresectable or metastatic NSCLC with ENHERTU based on the presence of activating HER2 (ERBB2) mutations detected by a validated test.

Patient Selection for Other Unresectable or Metastatic Solid Tumors

Select patients for treatment of unresectable or metastatic solid tumors based on HER2-positive (IHC 3+) tumor status.

Premedication

ENHERTU is emetogenic (see section 4.7 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information), which includes delayed nausea and/or vomiting. Prior to each dose of ENHERTU, patients should be premedicated with a combination regimen of two or three medicinal products (e.g., dexamethasone with either a 5-HT3 receptor antagonist and/or an NK1 receptor antagonist, as well as other medicinal products as indicated) for prevention of chemotherapy-induced nausea and vomiting.

Posology

The initial dose should be administered as a 90-minute intravenous infusion. If the prior infusion was well tolerated, subsequent doses of ENHERTU may be administered as 30-minute infusions.

The infusion rate of ENHERTU should be slowed or interrupted if the patient develops infusion related symptoms. ENHERTU should be permanently discontinued in case of severe infusion reactions.

Recommended Dosage for Metastatic Breast Cancer, Unresectable or Metastatic HER2-mutant NSCLC, and Other Unresectable or Metastatic Solid Tumors

The recommended dose 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 dose 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.

Dose Modifications

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

ENHERTU dose should not be re-escalated after a dose reduction is made.

Delayed or Missed Dose

If a planned dose is delayed or missed, it should be administered as soon as possible without waiting until the next planned cycle. The schedule of administration should be adjusted to maintain a 3-week interval between doses. The infusion should be administered at the dose and rate the patient tolerated in the most recent infusion.

Special Populations

Geriatrics

No dose adjustment of ENHERTU is required in patients aged 65 years or older.

Of the 2335 patients in clinical studies across multiple tumor types treated with ENHERTU 5.4 mg/kg, 28.9% were 65 years or older and 6.3% were 75 years or older. The incidence of Grade 3–4 adverse reactions observed in patients aged 65 years or older was 47.8% and in younger patients was 42.7%. There was a higher incidence of Grade 3–4 adverse reactions observed in patients aged 65 years or older (48.5%) as compared to younger patients (43.3%) in patients with HER2-positive breast cancer.

Of the 794 patients in clinical studies across multiple tumor types treated with ENHERTU 6.4 mg/kg, 38.7% were 65 years or older and 7.4% were 75 years or older. The incidence of Grade 3-4 adverse reactions observed in patients aged 65 years or older was 58.6% and in younger patients was 60.6%. There was a higher incidence of ≥Grade 3 adverse reactions observed in younger patients (87%) as compared to patients aged 65 years or older (76%) in patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01.

Population pharmacokinetic analysis indicates that age does not have a clinically meaningful effect on the pharmacokinetics of trastuzumab deruxtecan.

Pediatrics

The safety and efficacy in children and adolescents below 18 years of age have not been established as there is no relevant use in the pediatric population.

Renal Impairment

No dose adjustment is required in patients with mild (creatinine clearance [CLcr] ≥60 and <90 mL/min) or moderate (CLcr ≥30 and <60 mL/min) renal impairment. Limited data are available in patients with severe renal impairment. A higher incidence of Grade 1 and 2 ILD/pneumonitis leading to an increase in discontinuation of therapy has been observed in patients with moderate renal impairment. Patients with moderate or severe renal impairment should be monitored carefully (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Hepatic Impairment

No dose adjustment is required in patients with mild (total bilirubin ≤ULN and any AST >ULN or total bilirubin >1 to 1.5 times ULN and any AST) hepatic impairment. There are limited data to make a recommendation on dose adjustment in patients with moderate (total bilirubin >1.5 to 3 times ULN and any AST) hepatic impairment. No data are available in patients with severe (total bilirubin >3 times ULN and any AST) hepatic impairment.

Method of Administration

ENHERTU is for intravenous use. It must be reconstituted and diluted by a healthcare professional and administered as an intravenous infusion. ENHERTU must not be administered as an intravenous push or bolus.

For instructions on reconstitution and dilution of ENHERTU before administration, see section 6.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Contraindications

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.