An Improvement To The Standard Of Care

  • Data presented at this year’s ASCO conference indicates more people facing advanced breast cancer may be able to put off treatment with chemotherapy in favor of a more effective, targeted approach.
  • The DESTINY-Breast09 trial showed that starting treatment with trastuzumab deruxtecan (brand name: Enhertu) plus pertuzumab kept HER2+ advanced breast cancer from growing noticeably longer than the long-standing standard.
  • The trastuzumab deruxtecan plus pertuzumab approach reduced the risk of disease progression or death by 44% compared to the standard.

Data presented at 2025’s American Society of Clinical Oncology (ASCO) conference indicates that more people facing advanced breast cancer may be able to put off treatment with harsh chemotherapy in favor of a more effective, targeted approach.

The DESTINY-Breast09 trial showed that starting treatment with trastuzumab deruxtecan (brand name: Enhertu) plus pertuzumab kept advanced HER2+ breast cancer from growing noticeably longer than the long-standing standard — taxane, trastuzumab, and pertuzumab.

The results showed that the trastuzumab deruxtecan plus pertuzumab approach reduced the risk of disease progression or death by 44% compared to the standard.

The findings suggest that many women, and the smaller group of men who share this diagnosis, can postpone harsh chemotherapy and keep their cancer under control for longer.

“That’s where the clinically meaningful and statistically significant improvement in progression-free survival matters,” Dr. Nancy Chan, director for breast cancer clinical research at NYU Langone’s Perlmutter Cancer Center, tells SurvivorNet Connect. “…It translates into, for patients, not just a longer time period from progression, but also better quality of life.”

Why Do These Results Matter?

Twenty years ago, the outlook for stage 4 HER2+ disease felt bleak. Then came trastuzumab (brand name: Herceptin), a targeted antibody that blocks the HER2 signal. Adding pertuzumab (Perjeta) later improved the results further.

Oncologists combined both antibodies with a taxane chemotherapy drug in a regimen made famous by the CLEOPATRA trial. While CLEOPATRA gave patients precious months and even years without cancer progression, taxanes bring their own hardships in the form of side effects.

More recently, scientists designed antibody-drug conjugates (ADCs) that deliver a microscopic package of chemotherapy directly to HER2-laden cells. Trastuzumab deruxtecan, often shortened to T-DXd and marketed as Enhertu, is the most potent of those ADCs so far. Until today it sat in the second-line seat, offered after the cancer outgrew the standard of care drug cocktail.

DESTINY-Breast09 asked a simple question: Why wait to use the T-DXd approach?

DESTINY-Breast09: What Did The Data Show?

Results from the DESTINY-Breast09 trial were presented at the annual ASCO conference on June 2. They showed that the trastuzumab deruxtecan plus pertuzumab (T-DXd) approach reduced the risk of disease progression or death by 44% compared to the standard taxane, trastuzumab and pertuzumab (THP) approach as a first-line treatment for patients with HER2+ metastatic breast cancer.

The median progression-free survival was 40.7 months in the group given T-DXd compared to 26.9 months with THP.

Researchers were still tracking the overall survival for T-DXd compared to THP, but early data looks promising for the new, targeted approach as well.

“This study actually demonstrated that we’ve now managed to find a new therapy that improved upon the standard and this will impact many patients who have HER2+ breast cancer,” Dr. Chan explains.

How Will This Change Treatment Going Forward?

For more than a decade, the combination of a taxane, trastuzumab, and pertuzumab ruled as the standard treatment approach. DESTINY-Breast09 challenges that order. Many eligible patients will likely be eager to take the T-DXd plus pertuzumab route and avoid chemotherapy’s harsher toll.

However, several questions about the drug’s effectiveness remain, including:

  • How long should patients be on the drug? Should people stay on T-DXd indefinitely or take it for a fixed number of cycles then coast on the antibodies alone? The trial ran continuous dosing, but some doctors wonder if an “induction” phase followed by maintenance could slash ILD risk without losing control.
  • What comes after T-DXd? If T-DXd moves up, what comes second? Options include tucatinib-based triple therapy, the old CLEOPATRA trio, or antibody-drug conjugates that target different proteins. Trials are already mapping these paths.