When Enhertu stops working: What causes it and what comes after?

Enhertu has been making waves in the treatment of HER2-positive tumors since its approval. Its clinical trial results, particularly in metastatic breast cancer, have been referred to as "unheard of" ¹. The director of the Yale Cancer Center, Dr. Eric Winer, even called Enhertu a "new standard of care" ¹.

Unsurprisingly, this context sets a lot of expectations for patients. However, as far as cancer treatments go, there are no guarantees. No two patients get the same result. And for some patients, Enhertu stops working.

What happens after Enhertu, and what are some treatment options that you may still have? All you need to know at a glance.

How long is Enhertu effective?

Based on Enhertu clinical trial results, the medicine shows a median response duration of 11.3 months. In other words, for 50% of patients, Enhertu is likely to be effective for at least as long as 11.3 months. The other 50% may experience a shorter-term effect ².

Please keep in mind that results can vary across patients. Factors such as previous medical history or other conditions can influence medicine efficacy.

Why Enhertu stops working: Possible reasons

If you've started a treatment with Enhertu and have seen positive results, there are typically two reasons for Enhertu to stop working:

Side effects exceed the clinical benefit

Similar to other cancer medicines, Enhertu also comes with side effects. While some of them are mild and shouldn't affect your treatment, there are serious side effects as well. For example:

• allergic reactions

• serious lung conditions

• blood disorders, such as anemia

• reduced heart function.

   

If you're affected by a serious adverse effect, your doctor may decide to stop your Enhertu treatment and seek an alternative. Technically, this would not be because Enhertu isn’t working, but because the adverse effects have outweighed the clinical benefit for you. 

Immunotherapy resistance

A common occurrence with cancer immunotherapy is that cancer cells find ways to develop resistance to the effects of the treatment over time. This is known to happen with trastuzumab (one of Enhertu’s active ingredients).

Since Enhertu is a combination therapy (combining trastuzumab with chemotherapy), it may delay resistance. If we compare Enhertu vs Herceptin (trastuzumab) in terms of duration of response in HER2-positive metastatic breast cancer patients, Enhertu shows an advantage (18.5 months progression-free survival vs 7.8 months for Herceptin) ^3,4. However, even if Enhertu delays immunotherapy resistance, it does not prevent it.

What if you’re affected by trastuzumab resistance? There are still treatment options for you. Here are some.

What's after Enhertu: Some of your treatment options

Depending on your previous treatment regimens, your specific medical history, and the reason why Enhertu stopped working for you, the medicines below may be alternatives for your doctor to consider.

Enhertu alternatives for HER2-positive breast cancer

• Margenza (margetuximab-cmkb), possibly in combination with chemotherapy

Both Enhertu and Margenza are used in the treatment of HER2-positive metastatic breast cancer, after at least two prior rounds of treatment. However, they have different mechanisms of action.

Margenza is a monoclonal antibody that directly targets HER2. Unlike Enhertu, Margenza doesn't contain chemotherapy. Your doctor may prescribe it alongside chemotherapy.

Margenza is currently only approved in the USA. However, if you're based elsewhere, you can still access the medicine immediately as an Individual Named patient. Click below for more information.

Buy Margenza

 

• Kadcyla (trastuzumab emtansine)

Kadcyla is a medicine that combines trastuzumab with the chemotherapy drug emtansine. It's indicated for the treatment of advanced or metastatic HER2-positive breast cancer in adults who previously received trastuzumab and a taxane.

• Tukysa (tukatinib)

Tukysa is a kinase inhibitor approved for use alongside trastuzumab and capecitabine to treat metastatic HER2-positive breast cancer. This medicine also can be used in individuals with brain metastases.

Enhertu alternatives for HER2-positive gastric cancer

• Herceptin (trastuzumab)

Herceptin, which only contains the active ingredient trastuzumab, is indicated as a single agent for the treatment of metastatic HER2-positive gastric cancer. Usually, it is administered after chemotherapy treatment. Your doctor will determine whether it might be applicable to you as an alternative to Enhertu if you’ve had to discontinue your treatment.

Your doctor may consider these treatments after Enhertu stops working. He or she will determine whether they are suitable for your specific case.

What if an Enhertu alternative is not available in your country?

Has your doctor prescribed Margenza (margetuximab-cmkb) or another medicine that isn't available in your country yet? You don't have to wait for its approval to start your treatment. As an Individual Named Patient, you can buy any medicine that has been prescribed to you, before it's available locally.

At Everyone.org, we specialize in helping patients access the best treatment when they need it: now. If you have a prescription for Margenza or another Enhertu alternative that isn't available locally, get in touch, so we can help you access it.

Get in touch

References:

1. Kolata, Gina. Enhertu Breast Cancer Drug Results in ‘Unheard-of’ Survival Rates. The New York Times, 7 June 2022.
2. Efficacy Data | ENHERTU® (fam-trastuzumab deruxtecan-nxki). Enhertu, Accessed 8 January 2024.
3. Trastuzumab Genentech Herceptin. Accessdata.fda.gov, Accessed 8 January 2024.
4. USPI-DB-04 CDX Update FINAL. Daiichi Sankyo, Inc., Accessed 8 January 2024.