Infusion for the treatment of adults with inoperable or metastatic HER2-positive (IHC3+) solid tumours

About the medicinal product

Enhertu, containing the active substance trastuzumab deruxtecan, is used to treat adults with inoperable or metastatic (spread) HER2-positive (IHC3+)^[1] solid tumours.

HER2 is the abbreviation for human epidermal growth factor receptor 2. These receptors trigger division of cancer cells.

Enhertu is used after at least one prior systemic therapy^[2], if the disease is progressive^[3] and satisfactory alternative treatment options are no longer available.

The medicinal product Enhertu has already been authorised by Swissmedic for several other indications.

This indication extension for Enhertu was authorised in connection with "Project Orbis". Project Orbis is a programme for promising cancer treatments coordinated by the FDA, the US regulatory authority. It provides a framework for the concurrent submission and review of cancer medicines by several international partner authorities in various countries. The ultimate aim is to give patients faster access to innovative cancer treatments. In addition to the FDA, the authorisation authorities in Australia (TGA), Brazil (ANVISA), Israel (MOH), Canada (HC), Singapore (HSA), Switzerland (Swissmedic), and the United Kingdom (MHRA) are currently represented in Project Orbis.

^[1] _{IHC3+: Term used for strong staining of the protein HER2 on the surface of tumour cells. This means that the tumour forms particularly large amounts of HER2 proteins, which is important for the selection of specific targeted treatments.}

^[2] _{Systemic therapy: In contrast to local therapy (treatment at the site of the disorder), systemic therapy involves treatment of the entire body to eliminate a disorder.}

^[3] _{Progressive: The disease/tumour continues to progress, grow or spread despite treatment.}

Mode of action

Enhertu contains the active substance trastuzumab deruxtecan. This active substance combines an antibody (a protein) that can recognise and bind to the HER2 receptor on cancer cells with a substance known as a topoisomerase I inhibitor, which is effective against malignant tumours. As a result, the DNA (genetic material) of the tumour cells is damaged, leading to the death of the cancer cells.

Administration

Enhertu is a prescription-only medicine supplied as a powder for the preparation of a solution for infusion. Before use, the powder must be dissolved and diluted by a healthcare professional in accordance with the instructions and then infused slowly into the vein.

The recommended dose for metastatic or inoperable solid tumours is 5.4 mg/kg body weight. This dose is administered as an infusion once every three weeks and should be continued until the disease progresses or unacceptable side effects occur. 

Efficacy

The efficacy of Enhertu was investigated in clinical trials with 192 patients, all of whom had HER2-positive (IHC3+) inoperable or metastatic solid tumours and had already received prior treatments. The patients were enrolled in three phase II studies^[4]: DESTINY-PanTumor02, DESTINY-CRC02 and DESTINY-Lung01.

In these studies, the objective response rate (ORR)^[5] and the duration of response (DOR)^[6] were assessed by independent experts after the treatment with Enhertu.

The ORR was 51.4% in the DESTINY-PanTumor02 study, 52.9% in the DESTINY-Lung01 study and 46.9% in the DESTINY-CRC02 study.

The median DOR ranged from 5.5 months in DESTINY-CRC02, and 6.9 months in DESTINY-Lung01 to 19.4 months in DESTINY-PanTumor02.

Precautions, undesirable effects & risks

Enhertu must not be used in those who are hypersensitive to the active substance or any of the excipients.

While undergoing treatment with Enhertu, there is a risk of lung disease (interstitial lung disease, ILD) that can be potentially fatal. Patients should be monitored for signs such as coughing, shortness of breath, fever, or other respiratory symptoms.

Other very common undesirable effects after the administration of Enhertu include changes in blood cell counts, nausea, vomiting, fatigue, constipation, diarrhoea, and neutropenia^[7].

All precautions, risks, and other possible undesirable effects are listed in the Information for healthcare professionals.

^[4] _{Phase II study: Clinical trial in which a new medicinal product is tested in patients for efficacy and tolerability after its safety and dosage have been tested in phase I.}

^[5] _{Objective response rate (ORR): The objective response rate is defined as the percentage of patients with a clinically relevant reduction in tumour size.}

^[6] _{Duration of response (DOR): Period during which the tumour size is stably reduced or the tumour does not continue to grow following a response to treatment (i.e. the treatment was effective). The period ends when the tumour starts growing again or the disease has progressed.}

^[7] _{Neutropenia: Reduction in certain white blood cells that are important for fighting infections, resulting in an increased risk of infections.}

Why the medicinal product has been authorised

Limited treatment options are available for patients with inoperable or metastatic HER2-positive solid tumours (IHC3+) that have progressed after a prior systemic therapy and who do not have any satisfactory alternative treatment options. Enhertu offers a targeted treatment option specifically for this patient group.

The clinical trials (DESTINY-PanTumor02, DESTINY-CRC02, DESTINY-Lung01) showed clinically significant response rates and durations of response.

Although risks, including lung disease, exist, the clinically proven benefit outweighs these risks, particularly in patients with limited treatment options.

On the basis of the above, Swissmedic has extended the indication for the medicinal product Enhertu, containing the active substance trastuzumab deruxtecan, in Switzerland. Enhertu is now also authorised for the treatment of inoperable or metastatic HER2-positive solid tumours that have progressed after a prior systemic therapy or for which no other satisfactory treatment options are available.

This indication extension has been temporarily authorised under Article 9a TPA, since not all clinical trials had been completed or were available at the time of authorisation. The temporary indication extension is contingent on the timely submission of the additional data requested by Swissmedic. Once these authorisation conditions have been met, the temporary authorisation can be converted into an authorisation without special conditions in the event of a positive benefit-risk assessment of the results.

Further information on the medicinal product

Information for healthcare professionals:

Healthcare professionals can answer any further questions.

^{The date of revision of this text corresponds to that of the SwissPAR. New information concerning the authorised medicinal product in question will not be incorporated into the Summary report on authorisation.}

^{Swissmedic monitors medicinal products authorised in Switzerland. Swissmedic initiates the necessary action in the event of newly discovered adverse drug reactions or other safety-relevant signals. New findings that could impair the quality, efficacy, or safety of this medicinal product are recorded and published by Swissmedic. If necessary, the medicinal product information is adapted.}