Policy & Regulation
Enhertu Approved in the EU for the Treatment of HER2 Positive Metastatic Breast Cancer
21 January 2021 - - Japan-based pharmaceutical company Daiichi Sankyo Company, Ltd's (OTC: DSKYF) and British-Swedish pharmaceutical and biopharmaceutical company AstraZeneca's (OTC: AZNCF) Enhertu (trastuzumab deruxtecan) has been granted conditional approval in the European Union as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2 based regimens, the companies said.

In Europe, approximately 531,000 cases of breast cancer in women are diagnosed annually, with an estimated one in five cases being HER2 positive.

The impact of the disease is significant, with breast cancer responsible for more than 141,000 deaths per year in Europe.

Approval by the European Commission of Enhertu on January 18 was based on positive results from the single arm, pivotal phase 2 DESTINY-Breast01 trial.

After a median follow-up of 20.5 months, ENHERTU showed a confirmed objective response rate of 61.4%, including a 6.5% complete response rate and a 54.9% partial response rate, and an estimated median duration of response of 20.8 months in 184 patients with HER2 positive metastatic breast cancer who had received at least two previous lines of therapy.

This analysis was presented at the 2020 San Antonio Breast Cancer Symposium. A previous analysis with a median of 11.1 months of follow-up was published in The New England Journal of Medicine in February 2020.

The safety of ENHERTU has been evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2 positive breast cancer who received at least one dose of Enhertu 5.4 mg/kg in clinical studies. The median duration of exposure to Enhertu was 9.8 months (range: 0.7 to 37.1 months).

The most common adverse reactions were nausea (79.9%), fatigue (60.3%), vomiting (48.7%), alopecia (46.2%), constipation (35.9%), decreased appetite (34.6%), anemia (33.8%), neutropenia (32.5%), diarrhea (30.8%), thrombocytopenia (23.1%), cough (21.4%), leukopenia (20.5%) and headache (20.1%).
Cases of interstitial lung disease or pneumonitis were reported in 15.0% of patients.

In 2.6% of patients, ILD lead to death. Patients should be advised to immediately report cough, dyspnea, fever and/or any new or worsening respiratory symptoms.

Patients should be monitored for signs and symptoms of ILD or pneumonitis and those with suspected ILD or pneumonitis should be evaluated by radiographic imaging, preferably a computed tomography scan. Patients with a history of ILD or pneumonitis may be at increased risk.

In March 2020, the European Medicines Agency's Committee for Medicinal Products for Human Use granted ENHERTU accelerated assessment for the treatment of adults with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2 based regimens.

Approximately 531,000 cases of breast cancer are diagnosed in Europe annually, with an estimated one in five cases being HER2 positive.1,2,3 The impact of the disease is significant, with breast cancer responsible for more than 141,000 deaths per year in Europe.

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancers. HER2 overexpression may be associated with a specific HER2 gene alteration known as HER2 amplification and is often associated with aggressive disease and poor prognosis in breast cancer.

There remain significant unmet clinical needs for patients with HER2 positive metastatic breast cancer. The disease remains incurable with patients eventually progressing after currently available treatment options.

DESTINY-Breast01 is a pivotal phase 2, single-arm, open-label, global, multicenter, two-part trial evaluating the safety and efficacy of ENHERTU in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine.

The primary endpoint of the trial is objective response rate, as determined by independent central review.

Secondary objectives include duration of response, disease control rate, clinical benefit rate, progression-free survival and overall survival.

Enhertu (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the US only) is a HER2 directed antibody drug conjugate. Designed using Daiichi Sankyo's proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca's ADC scientific platform.

ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ('payload') to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Enhertu is comprised of a humanized anti-HER2 IgG1 monoclonal antibody with the same amino acid sequence as trastuzumab attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a tetrapeptide-based cleavable linker.

In addition to the approval in the EU, Enhertu (5.4 mg/kg) is approved in the US, under accelerated approval, and Japan, under the conditional early approval system, as a treatment for adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting based on the DESTINY-Breast01 trial.

Enhertu is also approved in the US and Japan (6.4 mg/kg) for the treatment of patients with HER2 positive unresectable advanced or recurrent gastric cancer that has progressed after a trastuzumab-containing regimen based on the DESTINY-Gastric01 trial.
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