Compared with doctors choice of chemotherapy, Enhertu (chemical name: fam-trastuzumab-deruxtecan-nxki) improved both progression-free survival and overall survival in people diagnosed with previously treated metastatic HER2-low breast cancer, according to a study.

The research was presented on June 5, 2022, at the American Society of Clinical Oncology (ASCO) Annual Meeting and published simultaneously in The New England Journal of Medicine. Read the abstract of Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer.

Progression-free survival is how long a person lives without the cancer growing. Overall survival is how long a person lives, whether or not the cancer grows.

Metastatic breast cancer is breast cancer that has spread to parts of the body away from the breast, such as the bones, liver, or brain.

Some breast cancer cells make, or overexpress, too many copies of the HER2 gene. The HER2 gene makes a protein known as a HER2 receptor. HER2 receptors are like ears, or antennae, on the surface of cells. These HER2 receptors receive signals that stimulate the cell to grow and multiply. But breast cancer cells with too many HER2 receptors can pick up too many growth signals and start growing and multiplying too much and too fast. Breast cancer cells that overexpress the HER2 gene are called HER2-positive.

Doctors use several tests to find out if a breast cancer is HER2-positive. Two of the most common are:

IHC (ImmunoHistoChemistry): The IHC test uses a chemical dye to stain the HER2 proteins. The IHC measures the amount of HER2 proteins on the surface of cells in a breast cancer tissue sample and gives it a score of 0 to 3+. If the score is 0 to 1+, its considered HER2-negative. If the score is 2+, its considered borderline. A score of 3+ is considered HER2-positive.

FISH (Fluorescence In Situ Hybridization): The FISH test uses special labels that attach to the HER2 proteins. The special labels have chemicals added to them so they change color and glow in the dark when they attach to the HER2 proteins. With the FISH test, you get a score of either positive or negative (some hospitals call a negative test result zero).

About 15% to 20% of breast cancers are HER2-positive. Still, research shows that more than 60% of breast cancers considered HER2-negative have some HER2 proteins on the surface of its cells. There just arent enough HER2 proteins for the cancer to be considered HER2-positive. Doctors now call these cancers HER2-low.

There are medicines called targeted therapies that specifically target the HER2 receptors on HER2-positive breast cancer cells. Herceptin (chemical name: trastuzumab) was the first anti-HER2 medicine developed. Still, these anti-HER2 medicines have not been effective against HER2-low breast cancers.

HER2-low breast cancer is commonly treated as if it were HER2-negative breast cancer, almost always with chemotherapy.

Enhertu is approved by the U.S. Food and Drug Administration (FDA) to treat unresectable or metastatic HER2-positive breast cancer in people who have previously received an anti-HER2 medicine:

for metastatic disease

before or after surgery for early-stage disease that came back (recurred) within six months of completing treatment

Unresectable means the cancer cant be removed with surgery.

Enhertu is a targeted therapy made up of three parts:

fam-trastuzumab: an anti-HER2 medicine that has the same basic structure as Herceptin

a topoisomerase I inhibitor chemotherapy called DXd: topoisomerase I inhibitors work by interfering with a cancer cells ability to replicate

a compound that links the fam-trastuzumab molecule to the topoisomerase I inhibitor chemotherapy molecule

Doctors call Enhertu an antibody-drug conjugate targeted therapy. The combination of the topoisomerase I inhibitor and the linking compound is called deruxtecan. The linking compound attaches (conjugates) the fam-trastuzumab to the topoisomerase I inhibitor chemotherapy.

Enhertu was designed to deliver the topoisomerase I inhibitor to cancer cells in a targeted way by attaching the topoisomerase I inhibitor to the fam-trastuzumab. The fam-trastuzumab part of Enhertu attaches to the HER2 protein, stopping it from receiving growth signals and also carries the topoisomerase I inhibitor to the cancer.

Because Enhertu contains both an anti-HER2 medicine and a chemotherapy medicine, the researchers for this study thought it might effectively treat HER2-low breast cancers.

Called DESTINY-Breast04, the study included 557 people 555 women and two men diagnosed with metastatic HER2-low breast cancer. The people joined the study between December 2018 and December 2021. All the people in the study had already received one or two lines of chemotherapy for metastatic disease.

In this study, the researchers defined breast cancer as HER2-low if it got an IHC score of 1+ or an IHC score of 2+ and a negative FISH test.

About 89% of the cancers in the study were hormone receptor-positive and about 11% were hormone receptor-negative.

About 45% of the people in the study lived in Europe or Israel and almost half were white.

The researchers randomly assigned the people to one of two treatment groups:

373 people received Enhertu; 331 (88.7%) of these people had hormone receptor-positive disease

184 people received their doctors choice of chemotherapy; 163 (88.6%) of these people had hormone receptor-positive disease

Among people who received their doctors choice of chemotherapy medicines:

51.1% received Halaven (chemical name: eribulin)

20.1% received Xeloda (chemical name: capecitabine)

10.3% received Abraxane (chemical name: albumin-bound or nab-paclitaxel)

10.3% received Gemzar (chemical name: gemcitabine)

8.2% received Taxol (chemical name: paclitaxel)

About 63% of people who received Enhertu and 61% of people who received their doctors choice of chemotherapy had previously received three or more types of treatment for metastatic disease.

The researchers followed about half the people for more than 18.4 months and half for less time.

As of Jan. 11, 2022, progression-free survival time was:

9.9 months for people who received Enhertu

5.1 months for people who received their doctors choice of chemotherapy

Overall survival time was:

23.4 months for people who received Enhertu

16.8 months for people who received their doctors choice of chemotherapy

The researchers also looked at specific subgroups of people in the study.

For people diagnosed with hormone receptor-positive disease:

progression-free survival was 10.1 months for people who received Enhertu and 5.4 months for people who received their doctors choice of chemotherapy

overall survival was 23.9 months for people who received Enhertu and 17.5 months for people who received their doctors choice of chemotherapy

For people diagnosed with hormone receptor-negative disease:

progression-free survival was 8.5 months for people who received Enhertu and 2.9 months for people who received their doctors choice of chemotherapy

overall survival was 18.2 months for people who received Enhertu and 8.3 months for people who received their doctors choice of chemotherapy

The researchers analyzed side effects in 371 people who received Enhertu and 172 people who received their doctors choice of chemotherapy.

More than 99% of the people who received Enhertu and more than 98% of people who received their doctors choice of chemotherapy had at least one side effect. About a quarter of the people in each treatment group had a serious side effect.

About 16% of people who received Enhertu and about 8% of people who received their doctors choice of chemotherapy stopped the medicine because of side effects.

The most common side effects of any grade among people receiving Enhertu were:

nausea, experienced by 73% of the people

fatigue, experienced by 47.7% of the people

hair loss, experienced by 37.7% of the people

The most common grade 3 or higher side effects among people receiving Enhertu were:

low white blood cell count, experienced by 13.7% of the people

low red blood cell count, experienced by 8.1% of the people

fatigue, experienced by 7.5% of the people

Interstitial lung disease, a general term for disorders that cause inflammation and scarring in the lungs, is a less common but serious side effect of Enhertu. Overall, 45 people who received Enhertu and one person who received the doctors choice of chemotherapy developed interstitial lung disease.

In the person who received the doctors choice of chemotherapy, the interstitial lung disease was grade 1.

Among the people who received Enhertu:

13 people had grade 1 interstitial lung disease

24 people had grade 2 interstitial lung disease

5 people had grade 3 interstitial lung disease

3 people had grade 5 interstitial lung disease

Overall, 14 people who received Enhertu and five people who received their doctors choice of chemotherapy died from drug-related causes during the study.

With these results, we have expanded the benefits of HER2 targeted therapy to a new population of breast cancer patients, said lead author Shanu Modi, MD, breast medical oncologist at Memorial Sloan Kettering Cancer Center when presenting the research. And [we] have established trastuzumab deruxtecan as the new standard of care for patients with HER2-low metastatic breast cancer. These findings have the potential to impact survival for approximately 50% of all patients diagnosed with metastatic breast cancer today.

If youve been diagnosed with metastatic breast cancer, the results of this study are extremely exciting and promising.

The attendees at the 2022 ASCO Annual Meeting were also excited. At the end of her presentation, Dr. Modi received a 40-second standing ovation.

The results of DESTINY-Breast04 are practice-changing, Dr. Modi said in an interview after her presentation. I think the strong efficacy of trastuzumab deruxtecan in this HER2-low patient population supports the need to now reclassify HER2-low as a new therapeutically targetable category of metastatic breast cancer.

Based on the results of the DESTINY-Breast04 study, you may want to talk to your doctor about the HER2 test results in your pathology report. If the score was 1+ on an IHC test or the score was 2+ on an IHC test plus a negative FISH test, Enhertu may be an option for you.

Learn more about Enhertu.

Written by: Jamie DePolo, senior editor

The rest is here:
A New Standard of Care? Enhertu Improves Survival in People With Metastatic HER2-Low Breast Cancer - Breastcancer.org

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