What is the success rate of Enhertu in metastatic breast cancer?

Key Points

In the DESTINY-Breast03 study in people with HER2-positive metastatic breast cancer, treatment with Enhertu (fam-trastuzumab deruxtecan-nxki) lengthened the amount of time people lived without their cancer getting worse (called median progression free survival or PFS) by 72% when compared to another HER2 inhibitor treatment called Kadcyla (ado-trastuzumab emtansine).

In the DESTINY-Breast06 study in people with HER2-low or HER2-ultralow metastatic breast cancer who had not received prior chemotherapy for advanced or metastatic disease, treatment with Enhertu lengthened median progression free survival (PFS) by 13.2 months compared to 8.1 months in those receiving their doctor's choice of chemotherapy treatment. This was equal to a 36% lower risk of disease progression or death.

Median progression-free survival is the amount of time that 50% of the people enrolled in studies were on treatment before their cancer started growing or spreading.

How is Enhertu used in metastatic breast cancer?

Enhertu is approved for three specific uses in metastatic breast cancer (has spread to other parts of the body) or that cannot be removed by surgery:

1. Enhertu (fam-trastuzumab deruxtecan) is approved to treat adults with human epidermal growth factor receptor 2 (HER2)-positive breast cancer that cannot be removed by surgery (unresectable) or that has spread to other parts of the body (metastatic), and who have received a prior anti-HER2-based regimen either:

• for metastatic disease, or
• have breast cancer that has come back during or within 6 months of completing treatment for their early-stage breast cancer.

This approval from May 2022 broadened the indications for Enhertu to be used earlier in HER2-positive metastatic breast cancer and it converted the FDA accelerated approval of Enhertu to regular approval.

2. Enhertu is also approved to treat HER2-low breast cancer that cannot be removed by surgery or that has spread to other parts of the body (metastatic), and who have received a prior chemotherapy for

• metastatic disease, or
• whose disease has returned during or within 6 months of completing adjuvant chemotherapy (after surgery).
• Eligible patients are determined by an FDA-approved test.

3. Enhertu is used for the treatment of adults with hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, that cannot be removed by surgery or has spread in the body (metastatic) and

• that has progressed on one or more endocrine therapies for metastatic disease.
• Eligible patients are determined by an FDA-approved test.

Administration

Enhertu is given as an intravenous (IV) infusion into your vein by a healthcare provider. You will normally receive this medicine one time every three weeks (on a 21-day treatment cycle) at your healthcare provider's office or at a local infusion center. Your healthcare provider will decide how many treatments you will need.

Enhertu may help people with cancer live longer and delay the progression of their disease, but keep in mind that your treatment results may differ from those seen in clinical studies. It’s always best to speak to your healthcare provider to determine the most effective and safe treatment for your condition and your expected results and timelines.

Enhertu is also approved by the FDA to treat non-small cell lung cancer with a that has a certain mutation in the HER2 gene, HER2-positive gastric or gastroesophageal junction adenocarcinoma (stomach cancer), and solid tumors that are HER2-positive (IHC 3+).

Enhertu is manufactured and marketed by AstraZeneca and Daiichi Sankyo.

Enhertu vs. Kadcyla in HER2-positive MBC

Researchers evaluated two primary endpoints - progression-free survival and overall survival - to see how effective Enhertu was compared to Kadcyla in patients with HER2-positive metastatic breast cancer (MBC) that could not be removed with surgery or that had spread, and who had received prior treatment. They also looked at a secondary endpoint, the overall response rate.

Kadcyla is another cancer medicine that is also used to treat HER2-positive metastatic breast cancer. It is usually given after other cancer medications have been tried without success.

Both Enhertu and Kadcyla are classified as HER2 inhibitors.

Progression-Free Survival

In studies, living longer without the cancer progressing is called progression-free survival. It is a common way researchers determine how well medicines work. Compared to Kadcyla, people receiving Enhertu were 72% more likely to be alive without cancer progression compared to Kadcyla. This result was found to be statistically significant, meaning it did not occur just by chance.

• The first time researchers looked at the data in DESTINY-Breast03 with 524 people in May 2021, they found that 174 of 261 of people (66.7%) who were treated with Enhertu lived without their cancer progressing or dying, compared to 105 of 263 people (39.9%) who received Kadcyla (ado-trastuzumab emtansine).
• Overall, 67% (174 of 261) of people treated with Enhertu were alive at the time of data analysis without their cancer progressing, compared to 40% (105 of 263) of people treated with Kadcyla.

Median progression-free survival (mPFS) is the amount of time it takes for the cancer to progress in the body or for death to occur in at least 50% of people in the study.

• In the review of results in May 2021, the mPFS for Enhertu had not been reached, meaning that more than 50% of patients had not yet had cancer progression or died. Comparatively, the mPFS for people taking Kadcyla was 6.8 months.
• When researchers looked at follow-up exploratory data in July 2022, they found that the mPFS with Enhertu was 28.8 months.

Overall Survival

Overall survival is another way researchers look at treatment effectiveness in cancer studies.

Overall survival (OS) is the length of time from either the date of diagnosis of the cancer or the start of treatment that patients diagnosed with the disease are still alive.

Overall survival rate is the percentage of people who are still alive at a certain time point after either the date of the diagnosis or the beginning of treatment.

In the initial review in May 2021, median overall survival data (in months) was not available. In the second review of data in July 2022, researchers found that people receiving Enhertu lived longer than people receiving Kadcyla.

• In the July 2022 review, more than 50% of all people in both groups were alive; but Enhertu reduced the overall risk of death compared to Kadcyla by 36% (hazard ratio = 0.64).
• Results showed that 170 of 261 people (65.1%) treated with Enhertu were alive at a median of 28.4 months while 138 of 263 people (52.4%) were alive at a median follow-up time of 26.5 months.
• The overall survival (OS) rate of people alive at 24 months was 77% in the group that received Enhertu and 70% with Kadcyla.

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Overall response rate

Overall response rate (ORR) is defined as the percentage of patients in a treatment group who have a partial or complete response to therapy over a certain time period. In studies, it helps to measure the cancer-killing properties of a medicine. ORR was a secondary outcome in DESTINY-Breast03 study.

In the initial review in May 2021, 83% (205 of 248) of people receiving Enhertu had their tumors shrink (the ORR) compared to 36% (87 of 241) of the people receiving Kadcyla.

In these studies, a complete response meant the tumor could not be seen on imaging tests and a partial response meant the tumor shrank by at least 30%. Not being able to see the cancer during imaging does always not mean the cancer is cured. Achieving stable disease meant that the tumor size did not increase by more than 20% or decrease by more than 30%.

• The data showed that 39 of 248 people (16%) receiving Enhertu and 20 of 241 people (8%) receiving Kadcyla had a complete response.
• Also, 166 of 248 people (67%) had a partial response with Enhertu compared to 67 of 241 people (28%) receiving Kadcyla.
• In addition, 37 of 248 people receiving Enhertu (15%) achieved stable disease vs. 97 of 241 (40%) receiving Kadcyla.

In the July 2022 assessment of data, 82% (202 of 246) of people receiving Enhertu had their tumors shrink (the overall response rate) compared to 37% (88 of 240) of people receiving Kadcyla.

• The updated data showed that 52 of 246 people (21%) receiving Enhertu achieved a complete response vs. 21 of 240 people (9%) receiving Kadcyla.
• A partial response was seen in 150 of 246 people receiving Enhertu (61%) compared to 67 of 240 people treated with Kadcyla (28%).
• In addition, 38 of 248 people receiving Enhertu (15%) achieved stable disease vs. 96 of 240 (40%) receiving Kadcyla.

Disease Control

In studies, the disease control rate is the percentage of people who have achieved a complete response, partial response or stable disease.

At both assessments in May 2021 and July 2022, 98% of patients treated with Enhertu had their tumors either shrink, stop growing, or slow down.

Enhertu in HER2-Low or HER2-Ultralow MBC

In some breast cancer cells, the human epidermal growth factor receptor 2 (HER2) protein is found on the cell surface and can cause cells to grow too quickly and spread. In some people with breast cancer identified as HER2-negative, low and ultra-low levels of the HER2 protein may still exist. These cells contain fewer HER2 proteins than do HER2-positive cancer cells, but may still be treated in some people. Your doctor will order an FDA-approved test to determine if you are eligible.

Enhertu was evaluated in the DESTINY-Breast06 Phase III trial in the treatment of 866 adults with hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, that could not be removed by surgery or that had spread in the body (metastatic), and had progressed on one or more endocrine therapies in metastatic disease. The primary outcome was progression free survival (PFS).

• Results showed a 36% reduction in the risk of disease progression or death versus chemotherapy (hazard ratio [HR] 0.64; 95% confidence interval [CI]: 0.54-0.76; p<0.0001) in the overall trial population of patients with chemotherapy-naïve HER2-low or HER2-ultralow metastatic breast cancer.
• A median progression-free survival (mPFS) of 13.2 months was seen in patients randomized to Enhertu compared to 8.1 months in those randomized to chemotherapy.
• The confirmed objective response rate (ORR) in the overall trial population was 62.6% for Enhertu versus 34.4% for chemotherapy.
• The median duration of response was 14.3 months (range: 0.4 to 39.6) for patients who received Enhertu compared to 8.6 months in the chemotherapy group.

Enhertu common side effects in breast cancer studies

All drugs can be associated with side effects and may occur frequently with cancer treatments. However, you may not experience all of the side effects listed below. Speak with your healthcare provider about the types of side effects you can expect and how to manage them.

The most common side effects with Enhertu in breast cancer studies (in at least 20% of people), including lab changes, were:

• Nausea
• Low white blood cell counts
• Low red blood cell counts
• Feeling tired, fatigue
• Low platelet counts
• Increased liver function blood tests
• Increased alkaline phosphatase
• Vomiting
• Hair loss
• Constipation
• Decreased appetite
• Low levels of blood potassium
• Diarrhea
• Muscle or bone pain
• Stomach-area pain

Your healthcare provider will give you medicines before your infusion to help prevent nausea and vomiting.

The Enhertu labeling also carries a Boxed Warning for Interstitial lung disease (ILD) and pneumonitis and harm to an unborn baby (embryo-fetal harm). A Boxed Warning is the FDA’s most stringent safety warning for a medication.

Tell your healthcare provider right away if you get any of the following symptoms of lung trouble:

• Cough
• Trouble breathing or shortness of breath
• Fever
• Other new or worsening breathing symptoms (such as chest tightness, wheezing).

Effective birth control (contraception) is required during treatment with Enhertu and for a period of months after treatment stops. If you are able to become pregnant, your healthcare provider should do a pregnancy test before you start treatment with Enhertu.

Your healthcare provider may reduce your dose, delay, or discontinue treatment with Enhertu if you have severe side effects. The most frequent adverse reactions (in at least 2% of patients) associated with a dose reduction were nausea, low white blood cells, and fatigue.

Related: Enhertu Warnings, Precautions and Side Effects (in more detail)

This is not all the information you need to know about Enhertu for safe and effective use and does not take the place of your doctor’s directions. Review the full patient medication guide and discuss this information and any questions you have with your doctor or other health care provider.