On April 20, 2021 Daiichi Sankyo UK, Limited (hereafter, Daiichi Sankyo) and AstraZeneca UK reported the news that the National Institute for Health and Care Excellence (NICE) has recommended Enhertu (trastuzumab deruxtecan) for use within the Cancer Drugs Fund (CDF) as an option for treating HER2 positive unresectable or metastatic breast cancer in adults who have received two or more prior anti-HER2 based therapies (Press release, Daiichi Sankyo, APR 20, 2021, View Source [SID1234578262]).
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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
"HER2 positive disease impacts one in five women with breast cancer, yet there is still no clear standard of care for patients with HER2 positive disease who have progressed following first-and second-line therapy," said Professor Peter Schmid, Barts Cancer Institute. "The availability of trastuzumab deruxtecan through NHS England’s Cancer Drugs Fund is good news for patients and brings an important new treatment option to those whose disease has continued to progress despite previous treatment."
"This authorisation is a significant step forward for the many thousands of people in England living with HER2 positive metastatic breast cancer," said Jo Taylor, founder of METUP UK, an advocacy group for people living with metastatic breast cancer. "Disease progression in metastatic breast cancer patients is an unmet need beyond second line treatment and new medicines are essential in the challenge to suppress this incurable disease."
This recommendation from NICE is based on the results of the single arm, multicentre, open label, phase 2 DESTINY-Breast01 trial of trastuzumab deruxtecan (5.4 mg/kg) in 184 patients with HER2 positive metastatic breast cancer who had received two or more prior anti-HER2-based therapies. Results from the data cut-off in June 2020 demonstrated a confirmed objective response rate (ORR) 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 34 (18.5%) treatment discontinuations due to treatment-emergent adverse events.6
"We are very proud to have worked with NICE, NHS England and the breast cancer community to make trastuzumab deruxtecan available, through the Cancer Drugs Fund, to eligible patients in England with HER2 positive metastatic breast cancer whose disease has progressed following treatment with two anti-HER2 directed therapies," said Haran Maheson, Commercial Director for Oncology, Daiichi Sankyo U.K.
"Though many treatment advances have been made in HER2 positive metastatic breast cancer, there has been no clear standard of care for patients following progression after second line treatment and many patients do not have a durable response to other available later-line options. To know that patients in England now have access to a new treatment option is welcome news indeed," said Arun Krishna, Head of Oncology, AstraZeneca U.K.
Daiichi Sankyo and AstraZeneca UK will continue working in close partnership with NICE as additional data are collected throughout the managed access period. During this time, eligible patients will be able to access trastuzumab deruxtecan in advance of a decision from NICE on routine funding on the NHS.
The CDF recommendation is applicable to patients in England. Discussions with Welsh and Northern Irish health authorities are ongoing and the submission for the appraisal of trastuzumab deruxtecan to the Scottish Medicines Consortium is currently in development, with a decision expected later in 2021.
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% of the 234 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
For further information about trastuzumab deruxtecan, such as the licensed indication and safety profile, please refer to the summary of product characteristics.
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. The disease remains incurable, with patients eventually progressing after currently available treatment options.8,9
About DESTINY-Breast01
DESTINY-Breast01 was 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 was confirmed ORR, as determined by independent central review. Key secondary objectives were disease control rate, clinical-benefit rate, duration of response, 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.
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.