Enhertu Gets FDA Approval for Treatment of Advanced HER2-positive Breast Cancer

Enhertu Gets FDA Approval for Treatment of Advanced HER2-positive Breast Cancer

The U.S. Food and Drug Administration (FDA) approved Enhertu (fam-trastuzumab deruxtecan-nxki) for the treatment of adults with inoperable or metastatic HER2-positive breast cancer who have received at least two prior anti-HER2-based regimens after their cancer had spread.

This accelerated approval comes just a few months after the agency agreed to review the application, under priority review. The medication should become available to patients in the U.S. in the coming weeks.

Accelerated approval is a form of conditional approval given to a medication that addresses an unmet need in a serious medical condition, providing it has shown benefits on surrogate or interim measures in a clinical trial. Enhertu’s continued use, and full approval, requires further verification and description of clinical benefit in a confirmatory study.

Enhertu, formerly known as DS-8201, is an antibody-drug conjugate consisting of the anti-HER2 antibody trastuzumab bound to the cancer-killing agent deruxtecan (a derivative of exatecan).

Jointly developed by Daiichi Sankyo and AstraZeneca, the therapy has been designed to deliver deruxtecan directly to HER2-positive cancer cells, improving specificity and reducing off-target effects when compared with conventional chemotherapy.

“The approval of Enhertu underscores that this specifically engineered HER2 directed antibody drug conjugate is delivering on its intent to establish an important new treatment for patients with HER2-positive metastatic breast cancer,” Antoine Yver, MD, executive vice president and global head of oncology research and development at Daiichi Sankyo, said in a press release.

“Since the beginning of our clinical trial program four years ago, we have focused on the opportunity to transform the treatment landscape for patients with HER2-positive metastatic breast cancer, and we are extremely proud of how quickly we delivered Enhertu to patients in the U.S., as Enhertu represents one of the fastest developed biologics in oncology,” Yver said.

FDA approval was based on data from the multicenter, single-arm Phase 2 DESTINY-Breast01 trial (NCT03248492).

DESTINY-Breast01 was designed to assess the safety and efficacy of trastuzumab deruxtecan at a dose of 5.4 mg per kilogram of body weight in 253 patients with inoperable and/or metastatic HER2-positive tumors who had been previously treated with at least two prior HER2 therapy regimens, including the antibody-drug conjugate Kadcycla (ado-trastuzumab emtansine).

The main goal of the study was to determine the percentage of patients achieving an objective response rate, i.e., those in whom the cancer disappeared (complete response) or shrank considerably after treatment (partial response).

Secondary objectives included duration of response, progression-free survival (the time patients lived without their disease worsening), and overall survival.

Of the first 184 women given Enhertu in the trial, 112 (60.9%) responded favorably to treatment, according to findings recently presented at the San Antonio Breast Cancer Symposium and published in The New England Journal of Medicine.  These included 103 (56%) who achieved a partial response and eight (4.3%) who achieved a complete response.

At a median follow-up of 11.1 months, the median time women lived without showing signs of disease progression was 16.4 months.

“Enhertu has shown impressive results in women with HER2 positive metastatic breast cancer, with the majority of women benefiting from treatment and the median duration of response exceeding 14 months,” said José Baselga, MD, PhD, executive vice president of Oncology Research and Development at AstraZeneca.

“With this first approval, we are proud to bring Enhertu to patients with high unmet need, and we look forward to further exploring its potential in additional settings,” Baselga said.

Enhertu’s safety was assessed in a separate pooled analysis that included data from 234 patients with inoperable or metastatic HER2-positive breast cancer who received at least one dose of the medication in DESTINY-Breast01 and in a prior Phase 1 trial (NCT02564900).

The most common adverse events reported in the studies included nausea, fatigue, vomiting, hair loss, constipation, decreased appetite, anemia, neutropenia (low white blood cell count), diarrhea, cough, and thrombocytopenia (low platelet count).

Six patients (2.6%) died due to complications caused by interstitial lung disease (ILD, scarring of lung tissue), which was reported in 9% of the participants, and pneumonitis.

Enhertu was approved with a boxed warning stating the medication has been associated with fatalities caused by ILD/pneumonitis and recommending patients stop treatment immediately if they start showing symptoms of these disorders.

In addition, the boxed warning  says exposure to the medication during pregnancy may harm the developing fetus, and advises all women taking Enhertu to ensure they use effective contraception.

Enhertu’s recommended dosing is 5.4 mg/kg given as an intravenous infusion once every three weeks until disease progression or unacceptable toxicity. Full prescribing information for Enhertu, including recommended dosing schedules and safety warnings, can be found here.