For UK media ONLY
- Marketing Authorisation based on the DESTINY-Breast01 trial
(16 February, 2021) Daiichi Sankyo UK, Limited(hereafter, Daiichi Sankyo) and AstraZeneca UK's Enhertu (trastuzumab deruxtecan) has been granted conditional authorisation in the UK 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.
In the UK, almost 54,000 cases of breast cancer in women are diagnosed 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 approximately 12,000 deaths per year.1 There are an estimated 35,000 people living with metastatic breast cancer in the UK, and in around 5% of women the breast cancer has already spread by the time it is diagnosed.4
"One in five women with breast cancer have HER2 positive disease. Though significant treatment advances have been made, there has been no clear standard of care for patients with metastatic HER2 positive disease following progression on first and second-line treatment and many patients do not have a durable response to other available later-line treatment options," said Dr Rebecca Roylance, Consultant Medical Oncologist, UCLH. "The authorisation of trastuzumab deruxtecan by the MHRA and EMA brings a new treatment option to patients and their doctors in the UK."
Authorisation is based on the results of the single arm, phase 2 DESTINY-Breast01 trial of trastuzumab deruxtecan (5.4 mg/kg) in 184 patients with HER2 positive metastatic breast cancer. Results from the data cut-off in June 2020 demonstrated a confirmed objective response rate of 61.4% (95% CI: 54.0-68.5), including a 6.5% complete response rate and a 54.9% partial response rate. After a median follow-up of 20.5 months, the median duration of response (DoR) was 20.8 months (95% CI: 15.0-NR).5 Trastuzumab deruxtecan showed a generally tolerable safety profile with 33 (17.9%) treatment discontinuations due to treatment-emergent adverse events.6
"Trastuzumab deruxtecan offers an important new option for patients with HER2 positive metastatic breast cancer in the UK who are in need of new treatment options after their cancer has progressed beyond both 1st and 2nd line therapy," said Haran Maheson, Commercial Director for Oncology, Daiichi Sankyo U.K. "This authorisation by the MHRA and EMA is the first for a medicine using our proprietary Dxd antibody drug conjugate technology and highlights the strength of the Daiichi Sankyo and AstraZeneca collaboration. We will now work closely in partnership with the MHRA to fulfil all regulatory requirements before stock can be available in the UK."
"The DESTINY-Breast01 trial showed a duration of response not previously seen in patients after progression on 1st and 2nd line treatment," said Arun Krishna, Head of Oncology, AstraZeneca U.K. "Trastuzumab deruxtecan is an important new treatment option for patients at this stage of care and will shift clinical discussions towards a focus on targeted treatment. This is the first new cancer medicine to be authorised by the MHRA in 2021 and our focus now is on securing access for NHS patients as quickly as possible."
The safety of trastuzumab deruxtecan 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 trastuzumab deruxtecan 5.4 mg/kg in clinical studies. The median duration of exposure to trastuzumab deruxtecan 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%), anaemia (33.8%), neutropenia (32.5%), diarrhoea (30.8%), thrombocytopenia (23.1%), cough (21.4%), leukopenia (20.5%), and headache (20.1%).5
Cases of interstitial lung disease (ILD) or pneumonitis were reported in 15.0% (n=234) of patients. Fatal outcomes were observed in 3% of patients. Patients should be advised to immediately report cough, dyspnoea, 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 (CT) scan. Patients with a history of ILD or pneumonitis may be at increased risk.5
Appraisals of trastuzumab deruxtecan by the National Institute of Health and Care Excellence and the Scottish Medicines Consortium are currently underway and NHS access decisions are expected later in 2021.
About HER2 positive breast cancer
HER2 is an epidermal growth factor receptor expressed on the surface of many types of tumours including breast cancer. 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.7
There remain significant unmet clinical needs for patients with HER2 positive metastatic breast cancer, since the disease remains incurable with patients eventually progressing after currently available treatment options.8,9
DESTINY-Breast01 is a phase 2, single-arm, open-label, global, multicentre, two-part trial evaluating the safety and efficacy of trastuzumab deruxtecan in patients with HER2 positive unresectable and/or metastatic breast cancer who had received two or more prior anti-HER2-based regimens, including trastuzumab emtansine (100%), trastuzumab (100%), and pertuzumab (65.8%). The primary endpoint of the trial is confirmed objective response rate, as determined by independent central review. Key secondary objectives were the disease control rate, clinical-benefit rate, duration of response and progression-free survival and safety.
About trastuzumab deruxtecan
Trastuzumab deruxtecan is a HER2 directed antibody drug conjugate (ADC). Designed using Daiichi Sankyo's proprietary DXd ADC technology, trastuzumab deruxtecan is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme 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. Trastuzumab deruxtecan is comprised of a humanised 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.
Trastuzumab deruxtecan (5.4 mg/kg) has also been granted conditional approval in the EU, under accelerated approval, 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 based on the DESTINY-Breast01 trial.
About the collaboration between Daiichi Sankyo and AstraZeneca
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialise trastuzumab deruxtecan in March 2019, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for the manufacturing and supply of trastuzumab deruxtecan.
About Daiichi Sankyo
Daiichi Sankyo Group is dedicated to the creation and supply of innovative pharmaceutical therapies to improve standards of care and address diversified, unmet medical needs of people globally by leveraging our world-class science and technology. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 15,000 employees around the world draw upon a rich legacy of innovation and a robust pipeline of promising new medicines to help people. In addition to a strong portfolio of medicines for cardiovascular diseases, under the Group's 2025 Vision to become a "Global Pharma Innovator with Competitive Advantage in Oncology," Daiichi Sankyo is primarily focused on providing novel therapies in oncology, as well as other research areas centred around rare diseases and immune disorders. For more information, please visit www.daiichi-sankyo.co.uk and follow Daiichi Sankyo UK on Twitter: @DaiichiSankyoUK.
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas Oncology, Cardiovascular, Renal Metabolism and Respiratory Immunology. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.
With its global headquarters in Cambridge, AstraZeneca operates in five different locations in the UK, where around 8,300 employees work in research and development, manufacturing, supply, sales and marketing. We supply 40 different medicines to the NHS. The UK is also an important location for AstraZeneca's clinical trials; in 2018, we undertook 201 trials in the UK, involving 376 centres and over 7,000 patients.
For more information, please visit www.astrazeneca.co.uk and follow us on Twitter @AstraZenecaUK
1 GLOBOCAN 2018. UK Cancer Fact Sheet. World Health Organization. Accessed: January 2021.
2 DeKoven M et al. J Comp Eff Res. 2012 ;1(5):453-63.
3 Sledge GW, et al. J Clin Oncol. 2014;32(19):1979-1986
4 Breast Cancer Now, 2020. Facts and Statistics 2020. Accessed: January 2021.
5 Medicines and Healthcare products Regulatory Agency. ENHERTU Summary of product characteristics.
6 Modi S et al. Presented at SABCS 2020 Poster PD3-06
7 Iqbal N Iqbal N. Mol Biol Int. 2014;852748.
8 de Melo Gagliato D, et al. Oncotarget. 2016;7(39):64431-46.
9 The National Comprehensive Cancer Network (NCCN). NCCN Guidelines Version 3.2020. Breast Cancer. June 2020.
ADC/21/0016 January 2021
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