ENHERTU

What it is

ENHERTU (trastuzumab deruxtecan) is a powder for injection supplied as 100 mg vials for reconstitution. This medicinal product is subject to additional monitoring in Australia due to approval of an extension of indication, which will allow quick identification of new safety information.

Approved indications

— Treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who previously received trastuzumab and a taxane for metastatic disease, or one prior anti-HER2-based regimen and developed disease recurrence during or within six months of completing neo-adjuvant or adjuvant therapy. — Treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-negative) breast cancer who have received prior 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 additionally have received and no longer be considered eligible for endocrine therapy. — Treatment of adult patients with unresectable or metastatic HR+ and either HER2-low (IHC 1+ or IHC 2+/ISH-negative) or HER2-ultralow (IHC 0 with membrane staining) breast cancer who have received at least one endocrine therapy in the metastatic setting and who are not considered suitable for endocrine therapy as the next line of treatment. — Treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior anti-HER2-based regimen. This indication was approved via the provisional approval pathway based on objective response rate, with continued approval depending on verification and description of benefit in a confirmatory trial. — Treatment of adult patients with unresectable or metastatic HER2-positive (IHC3+) solid tumours who have received prior systemic treatment and who have no satisfactory alternative treatment options. This indication was approved via the provisional approval pathway based on objective response rate, with full registration depending on submission of further clinical data to confirm clinical benefit. — Treatment of adult patients with unresectable or metastatic NSCLC whose tumours have activating HER2 (ERBB2) mutations and who have received prior platinum-based chemotherapy with or without immunotherapy. This indication was approved via the provisional approval pathway based on objective response rate, with continued approval depending on verification and description of benefit in a confirmatory trial.

Dosing overview

The initial dose should be administered as a 90-minute intravenous infusion; if the initial infusion is well tolerated, subsequent doses may be administered as 30-minute infusions. ENHERTU is emetogenic, which includes delayed nausea and/or vomiting; prior to each dose, 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.

Key safety warnings

Cases of interstitial lung disease (ILD) and/or pneumonitis have been reported with ENHERTU. Patients should be advised to immediately report cough, dyspnoea, fever, and/or any new or worsening respiratory symptoms. Patients should be monitored for signs and symptoms of ILD/pneumonitis, and evidence of ILD/pneumonitis should be promptly investigated. In patients who received ENHERTU 5.4 mg/kg in clinical studies across multiple tumour types, ILD occurred in 11.8% of patients as determined by independent review, with median time to first onset of 5.5 months. In patients treated with ENHERTU 6.4 mg/kg in clinical studies across multiple tumour types, ILD occurred in 16.8% of patients as determined by independent review, with median time to first onset of 4.2 months. Cases of neutropenia, including febrile neutropenia, were reported in clinical studies of ENHERTU. Complete blood counts should be monitored prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. Based on the severity of neutropenia, ENHERTU may require dose interruption or reduction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies. LVEF should be assessed prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. ENHERTU should be permanently discontinued if LVEF of less than 40% or absolute decrease from baseline of greater than 20% is confirmed, or in patients with symptomatic congestive heart failure. ENHERTU can cause fetal harm when administered to a pregnant patient. In post-marketing reports, use of trastuzumab, a HER2 receptor antagonist, during pregnancy resulted in cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Based on findings in animals and its mechanism of action, the topoisomerase I inhibitor component of ENHERTU can also cause embryo-fetal harm when administered to a pregnant patient. Patients who could become pregnant should be advised to use effective contraception during treatment and for at least 7 months following the last dose of ENHERTU.

Contraindications

There are no contraindications listed.

PBS listing

ENHERTU powder for intravenous infusion 100 mg is listed on the PBS with 4 items, authority required restriction, and an ex-manufacturer price of A$2493.06.

Regulatory history

ENHERTU (trastuzumab deruxtecan) 100 mg powder for injection was first listed on the ARTG on 8 October 2021. The initial approval date was 5 October 2021 for treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens, approved via the provisional approval pathway based on overall response rate and duration of response. In July 2022, PBAC did not recommend listing for HER2-positive metastatic breast cancer in patients whose disease had progressed following prior HER2-directed therapy. In December 2022, PBAC deferred the decision. In March 2023, PBAC recommended listing for HER2-positive metastatic breast cancer, with a deferred decision on inclusion of patients with more than two prior lines of therapy. In July 2023, PBAC recommended listing for breast cancer. In November 2023, PBAC did not recommend listing for HER2-low unresectable or metastatic breast cancer. In March 2024, PBAC recommended listing for HER2-low unresectable or metastatic breast cancer. In May 2025, the PBAC deferred a decision on metastatic HER2-positive gastric or gastroesophageal junction cancer following trastuzumab therapy.