Therapy Areas: Respiratory
Enhertu Granted Breakthrough Therapy Designation in US for Patients with HER2 Positive Metastatic Breast Cancer Treated with One or More Prior Anti-HER2-Based Regimens
4 October 2021 - - The US Food and Drug Administration has granted Enhertu (fam-trastuzumab deruxtecan-nxki) Breakthrough Therapy Designation in the US for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received one or more prior anti-HER2-based regimens.

Enhertu is a HER2 directed antibody drug conjugate jointly developed by Daiichi Sankyo company, Ltd. (hereafter, Daiichi Sankyo) and AstraZeneca.

The US FDA's BTD is designed to accelerate the development and regulatory review of potential new medicines that are intended to treat a serious condition and address a significant unmet medical need.

The new medicine needs to have shown encouraging preliminary clinical results that demonstrate substantial improvement on a clinically significant endpoint over available medicines.

Breast cancer remains the most common cancer worldwide, with more than two m cases diagnosed in 2020, resulting in nearly 685,000 deaths globally.

Approximately one in five cases of breast cancer are considered HER2 positive.

Despite initial treatment with trastuzumab and a taxane, patients with HER2 positive metastatic breast cancer will often experience disease progression.

More effective options are needed to further delay progression and extend survival.

The FDA granted BTD based on data from the DESTINY-Breast03 pivotal trial presented during the 2021 European Society for Medical Oncology Congress.

In the trial, Enhertu demonstrated a 72% reduction in the risk of disease progression or death compared to T-DM1 (hazard ratio [HR] = 0.28; 95% CI: 0.22-0.37; p=7.8x10-22) in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

The safety profile of the most common adverse events with Enhertu in DESTINY-Breast03 was consistent with previous clinical trials with no new safety concerns identified.

The most common grade 3 or higher drug-related treatment emergent adverse events in the Enhertu arm were neutropenia (19.1%), thrombocytopenia, leukopenia, nausea, anemia, fatigue, vomiting, increase in ALT, decreased appetite, increase in AST, diarrhea and alopecia.

Overall, 10.5% of patients had interstitial lung disease or pneumonitis related to treatment as determined by an independent adjudication committee. The majority of ILD events were low grade (grade 1 or grade 2) with two grade 3 events reported. No grade 4 or grade 5 ILD or pneumonitis events occurred.

Previous BTDs for ENHERTU were in late-line HER2 positive metastatic breast cancer in 2017 and HER2 mutant metastatic non-small cell lung cancer (NSCLC) and HER2 positive metastatic gastric cancer in 2020.

Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide. More than 2m cases of breast cancer were diagnosed in 2020, resulting in nearly 685,000 deaths globally. Approximately one in five cases of breast cancer are considered HER2 positive.

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 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.

Despite initial treatment with trastuzumab and a taxane, patients with HER2 positive metastatic breast cancer will often experience disease progression. More effective options are needed to further delay progression and extend survival.

DESTINY-Breast03 is a global, head-to-head, randomized, open-label, pivotal phase 3 trial evaluating the safety and efficacy of ENHERTU (5.4 mg/kg) versus T-DM1 in patients with HER2 positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

The primary efficacy endpoint of DESTINY-Breast03 is progression-free survival based on blinded independent central review. Secondary efficacy endpoints include overall survival, objective response rate, duration of response, progression-free survival based on investigator assessment and safety.

DESTINY-Breast03 enrolled 524 patients at multiple sites in Asia, Europe, North America, Oceania and South America.
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