First-Line Enhertu Combo Gets Priority Review in HER2+ Metastatic Breast Cancer

The U.S. Food and Drug Administration (FDA) has granted priority review to a supplemental biologics license application for first-line treatment with Enhertu (fam-trastuzumab deruxtecan-nxki; T-DXd) plus Perjeta (pertuzumab) for adults with unresectable or metastatic HER2-positive breast cancer, according to a news release from AstraZeneca.

“The DESTINY-Breast09 trial showed that treating patients with HER2-positive metastatic breast cancer with Enhertu in combination with [Perjeta] until progression in the first-line setting produced a new landmark of more than 40 months for progression-free survival and nearly doubled the number of patients with no evidence of disease on imaging,” Susan Galbraith, executive vice president of Oncology Haematology R&D at AstraZeneca, said in the news release. “This marks the first major evolution in treatment in this first-line setting in more than a decade — a setting where a strong response is crucial, as up to one-third of patients may not receive second-line therapy.”

Priority review status means the FDA will review the application more quickly than usual, as the combination therapy may provide meaningful improvements compared with current standard options.

A regulatory decision is expected during the first quarter of 2026. For patients, this means there may soon be an earlier opportunity to access a promising therapy that could help delay disease progression.

In addition to priority review, the FDA also granted breakthrough therapy designation to Enhertu plus Perjeta in this treatment setting. Breakthrough therapy designation is designed to accelerate the development and review of medicines that address serious conditions and meet an unmet medical need.

Phase 3 DESTINY-Breast09 Trial Results Showed Improved Outcomes

The FDA’s review is based on results from the phase 3 DESTINY-Breast09 trial. This study compared Enhertu plus Perjeta with the current standard treatment of a taxane chemotherapy, Herceptin (trastuzumab), and Perjeta — altogether referred to as THP — in patients receiving therapy for HER2-positive metastatic breast cancer for the first time.

Results showed that Enhertu plus Perjeta reduced the risk of disease progression or death by 44% compared with THP. Median progression-free survival was more than three years (40.7 months) for patients treated with the Enhertu-based approach, compared with 26.9 months for patients who received THP.

The benefits of Enhertu plus Perjeta were consistent across patient subgroups. The confirmed objective response rate was also higher in the Enhertu group at 85.1% compared with 78.6% with THP. Complete responses were achieved by 58 patients on Enhertu plus Perjeta compared to 33 on THP.

The safety profile of Enhertu plus Perjeta was consistent with what is already known for each therapy. No new safety concerns were identified, which suggests the combination can be given safely.

Will Enhertu Plus Perjeta Change the Standard of Care?

HER2-positive metastatic breast cancer is an aggressive form of the disease caused by the overexpression or amplification of the HER2 protein, the news release explained. It affects an estimated 15% to 20% of patients with metastatic breast cancer. Until now, THP has been the standard first-line regimen for more than a decade. However, the results from DESTINY-Breast09 suggest Enhertu plus Perjeta may offer a more effective option.

“Enhertu in combination with [Perjeta] delayed disease progression for more than three years compared with around two years with current standard of care as a first-line treatment for patients with HER2-positive metastatic breast cancer,” Ken Takeshita, global head of R&D at Daiichi Sankyo, added in the news release. “Receiving priority review moves us closer to offering Enhertu to patients even earlier in the metastatic treatment pathway as a potential new first-line treatment option.”

Notably, Enhertu, a HER2-directed antibody drug conjugate, is already approved in more than 85 countries as a second-line treatment for HER2-positive breast cancer based on results from the DESTINY-Breast03 trial. If the FDA approves this new first-line indication, Enhertu plus Perjeta may become the next standard of care for patients facing HER2-positive metastatic breast cancer, the news release concludes.

Reference

1. “ENHERTU® (fam-trastuzumab deruxtecan-nxki) plus pertuzumab granted Priority Review in the US as 1st-line treatment for patients with HER2-positive metastatic breast cancer,” by AstraZeneca. News release; Sept. 24, 2025.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.