Results consistent with previous trials, reinforcing benefit of
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
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, witha low rate of Grade 5 ILD events observed as determined by an independent adjudication committee.
The data will be presented at a forthcoming medical meeting.
Notes
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
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.
DESTINY-Breast02 enrolled approximately 600 patients at multiple sites in
Enhertu
Enhertu is a HER2-directed ADC. Designed using
Enhertu (5.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a (or one or more) prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.
Enhertu (5.4mg/kg) is approved in several countries 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 based on the results from the DESTINY-Breast01 trial.
Enhertu (5.4mg/kg) is approved in the US for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.
Enhertu (5.4mg/kg) is approved in the US for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours have activating HER2 (ERBB2) mutations, as detected by a
Enhertu (6.4mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.
Enhertu development programme
A comprehensive development programme is underway globally, evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.
Regulatory applications for Enhertu in breast and gastric cancer are currently under review in several countries based on the DESTINY-Breast01, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Gastric01 and DESTINY-Gastric02 trials,respectively.
Driven by a growing understanding of breast cancer biology,
PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in HER2-negative early and metastatic breast cancer patients with an inherited BRCA mutation.
Building on the initial approvals of Enhertu, in previously treated HER2-positive metastatic breast cancer,
To bring much needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer,
The Company's focus is on some of the most challenging cancers. It is through persistent innovation that
References
1. Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 10.3322/caac.21660.
2. Ahn S, et al. HER2 status in breast cancer: changes in guidelines and complicating factors for interpretation. J Pathol Transl Med. 2020; 54(1): 34-44.
3. Iqbal N, et al. Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications. Mol Biol Int. 2014; 852748.
4. Pillai R, et al. HER2 mutations in lung adenocarcinomas: A report from the
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