Enhertu Plus Perjeta: New First-Line Treatment for Metastatic HER2-Positive Breast Cancer?
People diagnosed with metastatic HER2-positive breast cancer who received Enhertu (chemical name: fam-trastuzumab-deruxtecan-nxki) and Perjeta (chemical name: pertuzumab) as a first treatment had a lower risk of the cancer growing or death than people who received the standard of care Taxol-Herceptin-Perjeta (THP) regimen.
The results from the DESTINY-Breast09 trial were presented at the 2025 American Society of Clinical Oncology Annual Meeting (ASCO).
Key takeaways
People who received Enhertu and Perjeta lived more than three years without the cancer growing (progression-free survival). Progression-free survival was more than two years for people who received THP chemo.
People who received Enhertu and Perjeta had a 44% lower risk of the cancer growing or dying from breast cancer than people who received THP chemo.
About 15% of cancers treated with Enhertu and Perjeta completely disappeared, called a complete response by doctors, compared to 8.5% of cancers treated with THP chemo.
What this means for you
These results suggest that Enhertu and Perjeta may be a better first-line treatment option for metastatic HER2-positive breast cancer than the THP chemo regimen. If you’ve been diagnosed with this type of breast cancer and are deciding on first treatments, you may want to talk to your doctor about this study.
Why do the study?
Results from the DESTINY-Breast02 and DESTINY-Breast03 studies confirmed Enhertu’s benefits for previously treated metastatic HER2-positive breast cancer. Enhertu is made up of Herceptin attached to deruxtecan, a chemotherapy medicine. So doctors wondered if Enhertu could take the place of Taxol and Herceptin in the THP chemo regimen that is the standard first-line treatment for metastatic HER2-positive disease.
About the study
DESTINY-Breast09 included 1,157 people diagnosed with metastatic HER2-positive breast cancer that hadn’t been treated with chemotherapy or an anti-HER2 medicine.
The people were randomly assigned to receive one of three treatments:
387 people received Enhertu and a placebo, an infusion that was just like Perjeta but contained no medicine
383 people received Enhertu and Perjeta
387 people received THP chemo
Half the people were followed for more than 2.5 years and half were followed for shorter amounts of time.
Detailed results
For this analysis, the researchers presented only information comparing Enhertu and Perjeta to THP chemo.
At two years, about 70% of the cancers treated with Enhertu and Perjeta hadn’t grown, compared to 52% of the cancers treated with THP chemo. About 85% of the cancers treated with Enhertu and Perjeta got smaller or disappeared compared to about 78% of cancers treated with THP chemo.
Overall survival is still being measured, but there was a trend toward better overall survival for people treated with Enhertu and Perjeta. Overall survival is how long people live, whether or not the cancer grows.
Rates of serious side effects were similar for both treatment groups, but people who received Enhertu and Perjeta stayed on the combination longer than people receiving THP chemo.
The results have the potential to establish a new standard of care for first-line treatment for metastatic HER2-positive breast cancer, explained lead author Sara Tolaney, MD, MPH, chief of the Division of Breast Oncology at the Dana-Farber Cancer Institute and associate professor of medicine at Harvard Medical School, who presented the results. “[First treatments for this type of cancer] haven’t seen significant innovation in more than a decade,” she said.
Whether or not the combination of Enhertu and Perjeta will prove to be better than Enhertu alone is not known at this time, and will be reported on at a later date.
Tolaney, S., et al. Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (a/mBC): Interim results from DESTINY-Breast09. 2025 ASCO Annual Meeting. Abstract LBA1008.
— Last updated on August 15, 2025 at 9:10 PM
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