Positive high-level results from the DESTINY-Breast02 Phase III trial of Enhertu (trastuzumab deruxtecan) versus physician’s choice of treatment showed the trial met the primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab emtansine (T-DM1). The trial also met the key secondary endpoint of improved overall survival (OS).
Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.
The trial evaluated a similar later-line patient population as the single-arm DESTINY-Breast01 Phase II trial, which was the basis for initial approvals in advanced HER2-positive metastatic breast cancer. The safety profile of Enhertu in DESTINY-Breast02 was consistent with previous Phase III clinical trials with no new safety concerns identified. Interstitial lung disease (ILD) rates and severity were consistent with those observed in other metastatic breast cancer trials of Enhertu, with a low rate of Grade 5 ILD events observed as determined by an independent adjudication committee.
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said, “The DESTINY-Breast02 trial results in this patient population with advanced disease confirm the efficacy and safety profile seen in DESTINY-Breast01 and are consistent with the results seen across our broader clinical programme in HER2-positive metastatic breast cancer. These data further strengthen our confidence in Enhertu and reinforce its potential to transform patient outcomes across multiple treatment settings.”
Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: “The top-line results from DESTINY-Breast02 confirm the robust progression-free survival seen in previous trials of Enhertu and enrich our clinical understanding of the benefit this therapy may offer patients with HER2-positive metastatic breast cancer. As this is the confirmatory trial for our current breast cancer indication in Europe and several other countries, we look forward to sharing these findings with regulatory authorities to add to the body of data for Enhertu for the treatment of HER2-positive metastatic breast cancer.”
The data will be presented at a forthcoming medical meeting.
HER2-positive breast cancer
Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide.1 More than two million patients were diagnosed with breast cancer in 2020, with nearly 685,000 deaths globally.1 Approximately one in five patients with breast cancer are considered HER2-positive.2
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast, gastric, lung and colorectal cancers.3 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.4
DESTINY-Breast02 is a global, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) versus physician’s choice of treatment (trastuzumab/capecitabine or lapatinib/capecitabine) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with T-DM1. Patients were randomised 2:1 to receive either Enhertu or physician’s choice of treatment.
The primary endpoint of DESTINY-Breast02 is PFS based on blinded independent central review (BICR). The key secondary endpoint is OS. Other secondary endpoints include objective response rate based on BICR and investigator assessment, duration of response based on BICR, PFS based on investigator assessment and safety.