Enhertu vs Herceptin: What is the difference between these HER2-mutated cancer treatments?

Last updated: 16 January 2024

For patients with a HER2-positive tumor, there are multiple third-line treatment options available. One of them is often a combination of chemotherapy and immunotherapy, such as Herceptin (trastuzumab). However, in recent years, there have been more and more alternatives available - including Margenza (margetuximab), Kadcyla (adu-trastuzumab emtansine), and Enhertu (fam-trastuzumab deruxtecan).

Having more treatment options is good news. However, it can be hard to understand how one medicine compares to another.

In this article, we'll focus on the similarities and differences between Herceptin and Enhertu. Including what types of HER2-positive cancers they can treat, and how you can access them if they're not available in your country yet.

Enhertu vs Herceptin: What are they used for?

Both Enhertu and Herceptin are used in the treatment of metastatic HER2-positive tumors. However, Enhertu is approved for more indications than Herceptin.

Herceptin is approved for the treatment of:

HER2-positive breast cancer (both early stage and metastatic);
HER2-positive metastatic gastric or gastroesophageal junction adenocarcinoma ².

Enhertu is approved for the treatment of:

HER2-positive metastatic breast cancer, which cannot be surgically removed;
HER2-low metastatic breast cancer, which cannot be removed by surgery;
HER2-positive advanced gastric cancer (stomach cancer) or gastro-oesophageal junction cancer.
HER2-mutant metastatic Non-Small Cell Lung Cancer ³.

You should keep in mind, though, that the indications for which Enhertu is approved may vary per country. For example, Enhertu's approval in the UK is only a fact for HER2-positive metastatic breast cancer.

Enhertu vs Herceptin: How do they work?

Similarities

Both Enhertu and Herceptin are targeted therapies. They are designed to bind to HER2 receptors on the surface of cancer cells. In this way, the medicines aim to stop the receptors from sending growth signals to cancer cells, effectively stopping the tumor from growing.

Differences

One of the biggest differences between Herceptin and Enhertu is that Enhertu combines immunotherapy and chemotherapy.

In addition to trastuzumab (an ingredient in both Enhertu and Herceptin), Enhertu also contains the chemotherapy agent deruxtecan. Because of that, Enhertu can deliver chemotherapy directly into the cancer cells, once it attaches to them.

How effective are Enhertu and Herceptin?

The safety and efficacy of Enhertu and Herceptin have been studied in multiple clinical trials. We'll look at them per indication below.

Early breast cancer

Herceptin clinical trial results

A meta-analysis of seven randomized trials of Herceptin in early-stage HER2-positive breast cancer reports these conclusions:

- The risks of breast cancer recurrence and death from breast cancer were lower with trastuzumab plus chemotherapy than with chemotherapy alone;
- The absolute 10-year recurrence risk was reduced by 9%, and the 10-year breast cancer mortality was reduced by 6.4% ⁴.
Enhertu clinical trial results

Enhertu has not been studied as a treatment in early breast cancer.

HER2-positive metastatic breast cancer

Herceptin clinical trial results

In a trial comparing Herceptin and chemotherapy against chemotherapy alone, these were the main findings:

- For 45% of patients treated with Herceptin and chemo the tumors shrank or disappeared (as compared to 29% of the chemo only group);
- Patients treated with Herceptin and chemo had a median time to progression of 7.2 months (as compared to 4.5 months for the chemo only group);
- The median duration of response was 8.3 months for the Herceptin and chemo patients. For the chemo only patients, it was 5.8 months ⁵.
Enhertu clinical trial results

The main outcomes of the DESTINY-Breast03 which compared Enhertu with Kadcyla (ado-trastuzumab emtansine) were:

- Tumors shrank or disappeared for 82.7% of Enhertu patients, as compared to 36.1% of Kadcyla patients;
- The median progression-free survival was 18.5 months for Enhertu patients and 5.6 months for Kadcyla patients ⁷.

Clinical trial results for Enhertu vs Herceptin as treatments for HER2-positive metastatic breast cancer

HER2-low metastatic breast cancer

Herceptin clinical trial results

Herceptin has not been studied as a treatment for HER2-low metastatic breast cancer.

Enhertu clinical trial results

In the DESTINY-Breast04 trial, Enhertu was studied against chemotherapy. The main reported outcomes were:

- Tumors shrank or disappeared for 52.3% of Enhertu patients, as compared to 16.3% of the chemo patients;
- Overall median survival was 23.4 months for Enhertu patients, as compared to 16.8 months for chemo patients;
- Median progression-free survival was 9.9 months for Enhertu patients and 5.1 months for chemo patients ⁷.

HER2-positive metastatic gastric cancer

Herceptin clinical trial results

Herceptin with chemotherapy was studied against chemotherapy alone. The main reported outcomes were:

- The median overall survival was 13.8 months for Herceptin patients, as compared to 11.1 months for chemo only patients ⁶;
- In a post hoc exploratory analysis, the patient subgroup with IHC2+/FISH+ or IHC3+ cancers had a 4.2 month prolongation of median overall survival with the addition of Herceptin to chemotherapy (16.0 versus 11.8 months) ¹³.
Enhertu clinical trial results

The DESTINY-Gastric01 trial compared Enhertu against chemotherapy. The main reported results were:

- Tumors shrank or disappeared for 40.5% of Enhertu patients, as compared to 11.3% of chemo patients;
- The median duration of response was 11.3 months for Enhertu and 3.9 months for chemo;
- Median overall survival was 12.5 months for Enhertu and 8.4 months for chemo ⁷.

Clinical trial highlights for Enhertu vs Herceptin in treating HER2-positive metastatic gastric cancer

HER2-mutant metastatic Non-Small Cell Lung Cancer

Herceptin clinical trial results

Herceptin hasn't been studied as a treatment for HER2-mutant NSCLC.

Enhertu clinical trial results

The DESTINY-Lung01 and DESTINY-Lung02 trials focused on Enhertu in different dosages. The main outcomes were:

- Tumors shrank or disappeared for 57.7% of Enhertu patients;
- The median duration of response was 8.7 months ⁷.

Enhertu vs Herceptin: Safety and side effects

Enhertu common side effects

In patients with metastatic breast cancer and HER2-mutated NSCLC:
- nausea
- decreased white blood cell count
- decreased hemoglobin
- decreased neutrophil count
- decreased lymphocyte count
- fatigue
- decreased platelet count
- increased aspartate aminotransferase
- vomiting
- increased alanine aminotransferase
- alopecia (hair loss)
- increased blood alkaline phosphatase
- constipation
- musculoskeletal pain
- decreased appetite
- hypokalemia
- diarrhea
- respiratory infection ⁷.
In patients with gastric cancer:
- decreased hemoglobin
- decreased white blood cell count
- decreased neutrophil count
- decreased lymphocyte count
- decreased platelet count
- nausea
- decreased appetite
- increased aspartate aminotransferase
- fatigue
- increased blood alkaline phosphatase
- increased alanine aminotransferase
- diarrhea
- hypokalemia
- vomiting
- constipation
- increased blood bilirubin
- fever
- alopecia (hair loss) ⁷.

Herceptin common side effects

In patients with adjuvant breast cancer:
- headache
- diarrhea
- nausea
- chills ².
In patients with metastatic breast cancer:
- fever
- chills
- headache
- infection
- congestive heart failure
- insomnia
- cough
- rash ².
In patients with metastatic gastric cancer:
- neutropenia
- diarrhea
- fatigue
- anemia
- stomatitis
- weight loss
- upper respiratory tract infections
- fever
- thrombocytopenia
- mucosal inflammation
- nasopharyngitis
- dysgeusia (metallic taste sensation) ².

Do you lose hair with Herceptin and Enhertu?

It depends on all the elements of your therapy.

Hair loss (alopecia) is not among the common side effects of Herceptin. Therefore, if you are prescribed Herceptin as a single agent (e.g. as a third-line therapy for HER2-positive breast cancer), you should not experience any hair loss. However, if your treatment combines Herceptin with chemotherapy, then you should refer to the patient information leaflets for your prescribed chemotherapy agent.

When it comes to Enhertu, hair loss is listed among the common side effects of the medicine. This is to be expected, as Enhertu contains a chemotherapy agent.

Do Herceptin and Enhertu cause weight gain?

Weight gain is not a known adverse effect of Herceptin (trastuzumab). However, if you're experiencing rapid weight gain during your Herceptin treatment, this may indicate a serious cardiovascular side effect. You should immediately consult with your doctor if in doubt ⁸.

Although not very common, weight gain can be a side effect of treatment with Enhertu.

Enhertu vs Herceptin: Price comparison

When it comes to medicines, the price always depends on your location. Final costs tend to vary depending on local approval, suppliers, or insurance coverage. Below is an indication of the costs of Herceptin and Enhertu, assuming no insurance coverage.

A single-dose vial of Enhertu costs approximately EUR 5,165. With the recommended dosage of one vial every 3 weeks, the yearly treatment costs for 1 person add up to about EUR 87,805 ⁹.

The indicative price of Herceptin per single-dose vial is EUR 1,534. In terms of yearly costs for 1 person, this comes up to EUR 79,768 ¹⁰.

Where are Enhertu and Herceptin approved?

Herceptin (trastuzumab) is widely approved, including in the USA, EU, UK, Japan, Australia and more. In recent years, biosimilar medicines have also started to gain approval around the world, including Herzuma, Ontruzant, Kanjinti and Trazimera.

Enhertu is approved in the USA, Japan, EU and the UK. However, it is not approved for all its indications everywhere.

Is Enhertu not (yet) approved or available in your country for the indication you need? If you and your doctor are of the opinion that this treatment might benefit you, get in touch with our team of Medicine Access experts. We can help you buy Enhertu immediately as an Individual Named Patient.

Get in touch to buy Enhertu