Enhertu Combo Receives FDA Designation in Metastatic HER2+ Breast Cancer

The FDA granted breakthrough therapy designation to first-line treatment with Enhertu plus Perjeta for unresectable or metastatic HER2+ breast cancer.

The United States Food and Drug Administration (FDA) has granted breakthrough therapy designation to first-line treatment with Enhertu (fam-trastuzumab deruxtecan-nxki) plus Perjeta (pertuzumab) for patients with unresectable or metastatic HER2-positive breast cancer, according to a news release from Daiichi Sankyo.

A breakthrough therapy designation is intended to expedite the development and review of novel treatments for individuals with serious conditions and limited therapeutic options. To be eligible, the investigational therapy must demonstrate early clinical evidence of significant improvement over current standard treatments.

The breakthrough therapy designation, in this case, was granted by the regulatory agency based on data from the DESTINY-Breast09 clinical trial. Data from the phase 3 study were shared during a special late-breaking oral session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

“This breakthrough therapy designation provides further recognition of the potential benefit of Enhertu in combination with Perjeta in the first-line setting of HER2-positive metastatic breast cancer,” said Dr. Ken Takeshita, global head of R&D at Daiichi Sankyo. “If approved, Enhertu will continue to redefine the treatment of metastatic breast cancer as these latest results from DESTINY-Breast09 demonstrate a median progression-free survival of more than three years when using Enhertu plus Pertuzumab in this disease setting, which is an improvement over the current standard of care that has been in place for more than a decade.”

Notably, this marks the ninth breakthrough therapy designation that has been granted to Enhertu. Of the nine total breakthrough designations granted for the therapeutic agent, five are for different types and stages of metastatic breast cancer, including HER2-positive and HER2-low or ultralow disease. Additionally, Enhertu has earned breakthrough therapy designations for the treatment of HER2-positive metastatic gastric and colorectal cancers, HER2-positive metastatic solid tumors, and HER2-mutant metastatic non-small cell lung cancer.

More Information on the DESTINY-Breast09 Clinical Trial

HER2-positive metastatic breast cancer is an aggressive form of the disease that affects approximately 15% to 20% of patients with metastatic breast cancer and is driven by overexpression or amplification of the HER2 protein. Although HER2-targeted therapies have improved outcomes, many patients experience disease progression within two years of first-line treatment, and nearly one-third receive no further therapy due to progression or death. The prognosis for this disease remains poor, highlighting the need for more effective treatment options. Therefore, investigators launched DESTINY-Breast09.

The global, multicenter, randomized, open-label DESTINY-Breast09 study evaluated the safety and efficacy of Enhertu either alone or in combination with Perjeta compared with the standard of care in patients with HER2 positive metastatic breast cancer being treated in the first line.

At the meeting, investigators reported that treatment with the first-line combination approach improved key survival outcomes compared with the standard care for those within the patient population.

“The combination of [Enhertu] and Perjeta, as we saw in DESTINY-Breast09, [nearly] doubled progression-free survival [for patients]. Therefore, I think [this treatment] does present a really nice new potential first-line therapy option for patients if they're newly diagnosed with metastatic HER2-positive positive breast cancer,” Dr. Sara M. Tolaney, DESTINY-Breast09 study author, explained in an interview with CURE.

Tolaney is a senior physician at Dana-Farber Cancer Institute and the chief of the Division of Breast Oncology at the Susan F. Smith Center for Women's Cancers, where she also serves as the associate director. Additionally, she is an associate professor of medicine at Harvard Medical School, located in Boston, Massachusetts.

The combination of Enhertu and Perjeta nearly doubled the time patients lived without their cancer worsening compared with standard-of care-treatment. Specifically, progression-free survival was 40.7 months with Enhertu and Perjeta versus 26.9 months with the standard of care, which translates to an improvement of nearly 14 months.

"Given these very significant improvements in progression-free survival, I believe Enhertu and Perjeta could be a new potential first-line treatment option for patients with metastatic HER2-positive breast cancer," Tolaney concluded in the interview with CURE.

References

1. "ENHERTU® Plus Pertuzumab Granted Breakthrough Therapy Designation in the U.S. as First-Line Therapy for Patients with HER2 Positive Metastatic Breast Cancer." News Release. Daiichi Sankyo.
2. “Trastuzumab deruxtecan plus Perjeta versus standard therapy for first-line HER2-positive advanced breast cancer” by Dr. Sara Tolaney, et al., Journal of Clinical Oncology.

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