Dato-DXd Seems Promising As New Treatment for Certain Metastatic Breast Cancers

The experimental medicine Dato-DXd may be a new treatment option for certain metastatic, hormone receptor-positive breast cancers.
Nov 2, 2023
 

A new targeted therapy medicine, Dato-DXd (datopotamab deruxtecan), offered better progression-free survival — which is how long a person lives without the cancer growing — than standard chemotherapy, according to a study. The medicine helped treat breast cancer with these characteristics: 

  • inoperable or metastatic

  • hormone receptor-positive, HER2-negative 

  • had grown during treatment with hormonal therapy

  • had been previously treated with chemotherapy

The research, “Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in previously treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer: Primary results from the randomized phase 3 TROPION-Breast01 trial,” was presented on Oct. 23, 2023, at the European Society for Medical Oncology (ESMO) Congress 2023.

Listen to the episode of The Breastcancer.org Podcast featuring Dr. Aditya Bardia discussing the TROPION-Breast01 study.

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Promising New Treatment for Metastatic Breast Cancer

Nov 2, 2023
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About Dato-DXd

Like Enhertu (chemical name: fam-trastuzumab-deruxtecan-nxki) and Trodelvy (chemical name: sacituzumab govitecan-hziy), Dato-DXd is a type of targeted therapy medicine called an antibody-drug conjugate.

Dato-DXd is made up of three parts:

  • datopotamab, a type of molecule called a monoclonal antibody, that targets the Trop-2 protein; the Trop-2 protein is found in about 80% of breast cancers

  • a topoisomerase I inhibitor chemotherapy called DXd; topoisomerase I inhibitors work by interfering with a cancer’s cells ability to replicate

  • a compound that links, or conjugates, the datopotamab to the DXd

 

About the study

Called TROPION-Breast01, the study included 732 people – 723 women and nine men – diagnosed with inoperable or metastatic, hormone receptor-positive, HER2-negative breast cancer that had been treated with one or two lines of chemotherapy. All the cancers had grown either while being treated with hormonal therapy or without hormonal therapy, for the people who couldn’t receive hormonal therapy.

The researchers split the people into two treatment groups:

  • 365 people received Dato-DXd once every three weeks

  • 367 people received their doctors’ choice of standard chemotherapy

For the second treatment group, the chemotherapy medicines used were:

  • Halaven (chemical name: eribulin), given on days one and eight of a three-week cycle

  • Navelbine (chemical name: vinorelbine), given on days one and eight of a three-week cycle

  • Gemzar (chemical name: gemcitabine), given on days one and eight of a three-week cycle

  • Xeloda (chemical name: capecitabine), taken as a pill for the first two weeks of a three-week cycle

The people stayed on the medicines until the cancer grew or they developed unacceptable side effects.

Better progression-free survival with Dato-DXd

Median progression-free survival was:

  • 6.9 months for people receiving Dato-DXd

  • 4.9 months for people receiving their doctors’ choice of chemotherapy

Median means half the people had a longer progression-free survival time and half the people had a shorter progression-free survival time.

This difference in progression-free survival was statistically significant, which means that it was likely due to the difference in treatment and not just because of chance.

The progression-free survival rates at nine months were: 37.5% in the Dato-DXd group and 18.7% in the doctors’ choice of chemotherapy group.

“The nine-month progression-free survival rates were almost double with Dato-DXd compared to investigators’ choice of chemotherapy,” said Aditya Bardia, MD, MPH, associate professor at Harvard Medical School and director of breast cancer research at Massachusetts General Hospital, who presented the research.

The overall survival data – how long the people lived whether the cancer grew or not – were not ready for this presentation, but Dr. Bardia said there was a trend that favored Dato-DXd. The next analysis will include overall survival information.

Other results

People also were able to stay on Dato-DXd longer than chemotherapy. Median treatment time was:

  • 6.7 months for people in the Dato-DXd group

  • 4.1 months for people in the chemotherapy group

After about 11 months of follow-up, 93 people in the Dato-DX group were still receiving the medicine and 39 people in the doctors’ choice of chemotherapy were still receiving chemotherapy.

This means that about three times the number of people were still receiving Dato-DXd compared to people still receiving chemotherapy.

Dr. Bardia explained that most of the people who stopped treatment stopped because the cancer grew.

Side effects

Like most breast cancer medicines, Dato-DXd can cause side effects. In this study, 94% of people receiving Dato-DXd and 86% of people receiving chemotherapy had one or more side effects.

Still, people receiving Dato-DXd experienced less severe side effects compared to people receiving chemotherapy. The rates of side effects that were grade three (meaning they were severe but not life-threatening) or higher were:

  • 21% in the Dato-DXd group

  • 45% in the chemotherapy group

Side effects led to a dose reduction in 21% of the people receiving Dato-DXd and 30% of the people receiving chemotherapy.

The most common side effects caused by Dato-DXd were:

“Overall results support Dato-DXd as a potential new therapeutic option for patients with metastatic hormone receptor-positive breast cancer,” Dr. Bardia concluded.

 

What this means for you

Editor's Note: On Jan. 17, 2025, the U.S. Food and Drug Administration approved Dato-DXd to treat adults diagnosed with unresectable or metastatic hormone receptor-positive, HER2-negative breast cancer that grew during previous treatment with hormonal therapy and chemotherapy. Unresectable means the cancer can't be removed with surgery.

If you’ve been diagnosed with this type of breast cancer, you may want to talk to your doctor about Dato-DXd to learn if it might be a good fit for you and your unique situation.

— Last updated on May 1, 2025 at 4:41 PM

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