Enhertu Gets Breakthrough Therapy Designation for HER2-Low/Ultralow Breast Cancer

The FDA will speed up its review of Enhertu for certain patients with breast cancer.

The Food and Drug Administration (FDA) granted a breakthrough therapy designation to Enhertu (fam-trastuzumab deruxtecan-nxki) for the treatment of patients with unresectable (unable to be removed by surgery) or metastatic HR-positive, HER2-low or -ultralow breast cancer.

Specifically, the indication is for disease that has been previously treated with either two lines of endocrine therapy in the metastatic setting, or one line of endocrine therapy if the disease progressed within six months of starting the initial endocrine treatment combined with a CDK4/6 inhibitor or within two years of starting postsurgical endocrine therapy, according to a press release from Daiichi Sankyo, the manufacturer of the drug.

Breakthrough therapy designations, according to the FDA, are intended to speed up the development and potential approval of drugs intended to treat serious conditions or diseases.

“If approved, Enhertu could once again change the treatment paradigm for certain patients with breast cancer, pushing past old boundaries and broadening the number of people who may be eligible for a HER2-directed therapy,” Dr. Ken Takeshita, Global Head, R&D at Daiichi Sankyo, said in the release announcing the breakthrough therapy designation.

DESTINY-Breast06 Study, Outcomes

The FDA’s decision is based on data from the phase 3 DESTINY-Breast06 trial, which were presented at the 2024 American Society of Clinical Oncology Annual Meeting.

Researchers conducting the DESTINY-Breast06 trial compared the safety and efficacy of Enhertu with investigator’s choice of chemotherapy (capecitabine, paclitaxel or nab-paclitaxel) in HR-positive, HER2-low or -ultralow advanced or metastatic breast cancer. The main goals of the trial were to see which treatment group had better progression-free survival (PFS; time after treatment patients live until their disease worsens), as well as overall survival (OS; time from treatment until death of any cause). The researchers also analyzed objective response rate (ORR; percentage of patients whose disease shrinks or disappears from treatment), duration of response, time to next treatment or death, time to second subsequent treatment or death, and safety.

For patients with HER2-low disease, median PFS in the Enhertu group was 13.2 months, compared with 8.1 months in the chemotherapy group. For those with HER2-ultralow cancer, median PFS was 13.2 months and 8.3 months in the Enhertu and chemotherapy groups, respectively.

READ MORE: Enhertu Boosts PFS in Pretreated, HR-Positive, HER2-Low and -Ultralow Breast Cancer

At the time the research was presented in June, the OS data were not yet mature, meaning that not enough patients had died for researchers to calculate an average time until death.

About Enhertu and HER2 Expression in Breast Cancer

Enhertu is an antibody drug conjugate, which is a type of drug that targets a specific protein on cancer cells — in this case HER2. Once the drug binds to the cells, it releases a cancer-killing proponent.

Traditionally, clinicians divided patients into two different HER2 statuses: HER2-positive and HER2-negative. However, more recently, researchers have added the HER2-low classification for patients who do not quite meet the HER2-positive criteria, but still have some HER2 expression on their cancer cells.

According to the press release from Daiichi Sankyo, it is estimated that approximately 60-65% of HR-positive, HER2-negative breast cancers are HER2-low. Up to 25% may also be HER2-ultralow.

In 2022, Enhertu was approved for unresectable or metastatic HER2-low breast cancer, marking the first targeted therapy for HER2-low disease.

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