2023 Februarie: Enhertu (trastuzumab deruxtecan) from AstraZeneca and Daiichi Sankyo has been approved as a monotherapy 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 specifically engineered HER2-directed antibody drug conjugate (ADC) that AstraZeneca and Daiichi Sankyo are jointly developing and commercialising.
In the DESTINY-Breast03 Phase III trial, Enhertu demonstrated a 72% reduction in the risk of disease progression or death compared to trastuzumab emtansine (T-DM1) (hazard ratio [HR] 0.28; 95% confidence interval [CI] 0.22-0.37; p0.000001) in patients with HER2-positive unresectable and/or metastatic borskanker previously treated with trastuzumab and a taxan
In China, breast cancer is the most prevalent cancer among women, with over 415,000 cases expected to be diagnosed in 2020.
1 Approximately 18% of global breast cancer deaths occurred in China in 2020, with nearly 120,00 deaths attributable to breast cancer. 1 Approximately one out of every five cases of breast cancer is HER2-positive. 2
Binghe Xu, MD, Professor and Director of the Department of Medical Oncology, Cancer Hospital and Institute Cancer Hospital, Chinese Academy of Medical Sciences, stated, “This approval represents a significant milestone for the breast cancer community in China, as patients with HER2-positive metastatic breast cancer continue to require additional treatment options. Despite initial treatment, patients with HER2-positive metastatic breast cancer frequently experience disease progression, demonstrating the importance of early systemic disease control and the potential for Enhertu to assist patients with metastatic breast cancer who are eligible for treatment.”
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, stated, “This first approval of Enhertu in China represents a significant advancement in the treatment of HER2-targetable tumours and offers patients with previously treated HER2-positive metastatic breast cancer the opportunity to benefit from this important medication as a second line therapy. The approval demonstrates our commitment to patients in China, where the incidence of breast cancer has increased, as we continue to investigate the potential benefits of Enhertu in the treatment of HER2-directed metastatic breast cancer and other HER2-targetable cancers.
Kiminori Nagao, Head of Daiichi Sankyo’s Asia, South and Central America (ASCA) Business Unit, stated, “Enhertu is extending the time before disease progression or death and helping to redefine outcomes for patients with previously treated HER2-positive metastatic breast cancer, and now physicians in China will have access to this important medicine for their patients. With this approval, Enhertu has the potential to become a new standard of care in China for patients with HER2-positive metastatic breast cancer in the second-line setting.”
In DESTINY-Breast03, Enhertu’s safety profile was looked at in 257 patients with HER2-positive breast cancer that could not be removed or had spread to other parts of the body. It was similar to what had been seen in previous kliniese proewe, and no new safety concerns were found. Nausea (75.9%), fatigue (49.4%), vomiting (49.0%), neutropenia (42.8%), and alopecia (37%) were the most common adverse reactions.
This approval follows China’s NMPA’s Breakthrough Therapy Designation and Priority Review of Enhertu for this type of breast cancer in 2022.
Notes
Borskanker en HER2 uitdrukking
Breast cancer is the most common cancer and one of the leading causes of cancer-related deaths worldwide.3 Meer as twee miljoen pasiënte is in 2020 met borskanker gediagnoseer, met byna 685,000 XNUMX sterftes wêreldwyd.3 In China, breast cancer is the most common cancer in women, with more than 415,000 patients diagnosed in 2020.1 There were nearly 120,000 breast cancer deaths in China in 2020, representing approximately 18% of global breast cancer deaths.1 Approximately one in five cases of 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.4 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and a poor prognosis in breast cancer.5
Despite initial treatment with trastuzumab and a taxane, patients with HER2-positive metastatic breast cancer will often experience disease progression.6,7
DESTINY-Bors03
DESTINY-Breast03 is 'n wêreldwye, kop-aan-kop, gerandomiseerde, oop-etiket, registrasie Fase III proef wat die doeltreffendheid en veiligheid van Enhertu (5.4mg/kg) teenoor T-DM1 by pasiënte met HER2-positiewe onopereerbare en/of metastatiese borskanker wat voorheen met trastuzumab en 'n taksaan behandel is.
The primary efficacy endpoint of DESTINY-Breast03 is progression-free survival (PFS) based on blinded independent central review (BICR). Overall survival (OS) is a key secondary efficacy outcome measure. Other secondary efficacy endpoints include objective response rate (ORR), duration of response, PFS based on investigator assessment and safety. Primary results from DESTINY-Breast03 were published in Die New England Journal of Medicine,8 with updated PFS and OS results published in The Lancet.9
DESTINY-Breast03 enrolled 524 patients at multiple sites in Asia, Europe, North America, Oceania and South America.
Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.
Enhertu (5.4mg/kg) is approved in more than 40 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 more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in-situ hybridization [ISH]-) breast cancer who have received a prior systemic therapy 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 under accelerated approval in the US for the treatment of adult patients with unresectable or metastatic longkanker wat nie klein is nie whose tumours have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Enhertu (6.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenokarsinoom who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial and/or DESTINY-Gastric02 trial.
Enhertu ontwikkelingsprogram
A comprehensive global development programme is underway evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers including breast, gastric, lung and kolorektale kanker. Trials in combination with other anticancer treatments, such as immunotherapie, are also underway.
Daiichi Sankyo samewerking
Daiichi Sankyo Company, Limited (TSE: 4568) [na verwys as Daiichi Sankyo] en AstraZeneca het 'n wêreldwye samewerking aangegaan om gesamentlik te ontwikkel en te kommersialiseer Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu en datopotamab deruxtecan.
AstraZeneca in borskanker
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.
AstraZeneca het 'n omvattende portefeulje van goedgekeurde en belowende verbindings in ontwikkeling wat verskillende meganismes van werking gebruik om die biologies diverse borskankertumor-omgewing aan te spreek.
Met Enhertu (trastuzumab deruxtecan), a HER2-directed ADC, AstraZeneca and Daiichi Sankyo are aiming to improve outcomes in previously treated HER2-positive and HER2-low metastatic breast cancer and are exploring its potential in earlier lines of treatment and in new breast cancer settings.
In HR-positive breast cancer, AstraZeneca continues to improve outcomes with foundational medicines Faslodex (fulvestrant) en Zoladex (goserelin) and aims to reshape the HR-positive space with next-generation SERD and potential new medicine camizestrant, as well as a potential first-in-class AKT kinase inhibitor, capivasertib. AstraZeneca is also collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan, in this setting.
PARP -remmer Lynparza (olaparib) is a targeted treatment option that has been studied in early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca and MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in these settings and to explore its potential in earlier diseases.
To bring much-needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is evaluating the potential of datopotamab deruxtecan alone and in combination with immunotherapy Imfinzi (durvalumab), capivasertib in combination with chemotherapy, and Imfinzi in combination with other oncology medicines, including Lynparza en Enhertu.
AstraZeneca in onkologie
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop, and deliver life-changing medicines to patients.
The company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.
AstraZeneca het die visie om kankersorg te herdefinieer en kanker eendag uit te skakel as oorsaak van dood.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries, and its innovative medicines are used by millions of patients worldwide.
Verwysings
1. Wei Cao, et al. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020. Chin Med J (Engels). 2021 Apr 5; 134(7): 783–791.
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. Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Kanker J Clin. 2021; 10.3322/caac.21660.
4. Iqbal N, et al. Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications. Mol Biol Int. 2014; 852748.
5. Pillai R, et al. HER2 mutations in lung adenocarcinomas: A report from the Long kanker Mutation Consortium. Kanker. 2017;1;123(21):4099-4105.
6. Barok M, et al. Trastuzumab emtansine: mechanism of action and drug resistance. Breast Cancer Res. 2014; 16 (2): 209.
7. Nader-Marta G, et al. How we treat patients with metastatic HER2-positive breast cancer. ESMO oop. 2022; 7:1.
8. Cortes J, et al. Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer. N Engl J Med. 2022; 386: 1143-1154.
9. Hurvitz S, et al. Trastuzumab deruxtecan versus trastuzumab emtansine in patients with HER2-positive metastatic breast cancer: updated results from DESTINY-Breast03, a randomised, open-label, phase 3 trial. Lancet. 2022 Dec 6;S0140-6736(22)02420-5.
