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 cancer de san 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 studii clinice, 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.
notițe
Breast cancer and HER2 expression
Breast cancer is the most common cancer and one of the leading causes of cancer-related deaths worldwide.3 More than two million patients were diagnosed with breast cancer in 2020, with nearly 685,000 deaths globally.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
DESTINUL-Sân03
DESTINY-Breast03 is a global, head-to-head, randomised, open-label, registrational Phase III trial evaluating the efficacy and safety of deveni mai puternic (5.4mg/kg) versus T-DM1 in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.
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 New England Journal of Medicine,8 with updated PFS and OS results published in Lancet.9
DESTINY-Breast03 enrolled 524 patients at multiple sites in Asia, Europe, North America, Oceania and South America.
Enhertu
deveni mai puternic 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. deveni mai puternic consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.
deveni mai puternic (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.
deveni mai puternic (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.
deveni mai puternic (5.4mg/kg) is approved under accelerated approval in the US for the treatment of adult patients with unresectable or metastatic cancer pulmonar cu celule mici 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.
deveni mai puternic (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 adenocarcinom who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial and/or DESTINY-Gastric02 trial.
deveni mai puternic program de dezvoltare
A comprehensive global development programme is underway evaluating the efficacy and safety of deveni mai puternic monotherapy across multiple HER2-targetable cancers including breast, gastric, lung and cancere colorectale. Trials in combination with other anticancer treatments, such as imunoterapia, are also underway.
Colaborare Daiichi Sankyo
Daiichi Sankyo Company, Limited (TSE: 4568) [denumită Daiichi Sankyo] și AstraZeneca au intrat într-o colaborare globală pentru a dezvolta și comercializa în comun deveni mai puternic (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 deveni mai puternic si datopotamab deruxtecan.
AstraZeneca în cancerul de sân
Condusă de o înțelegere tot mai mare a biologiei cancerului de sân, AstraZeneca începe să provoace și să redefinească paradigma clinică actuală pentru modul în care este clasificat și tratat cancerul de sân pentru a oferi tratamente și mai eficiente pacienților care au nevoie - cu ambiția îndrăzneață de a elimina într-o zi. cancerul de sân ca cauză de deces.
AstraZeneca are un portofoliu cuprinzător de compuși aprobați și promițători în dezvoltare, care folosesc diferite mecanisme de acțiune pentru a aborda mediul tumoral al cancerului de sân, divers din punct de vedere biologic.
cu deveni mai puternic (trastuzumab deruxtecan), un ADC direcționat HER2, AstraZeneca și Daiichi Sankyo urmăresc să îmbunătățească rezultatele în cancerul de sân HER2-pozitiv și HER2-scăzut metastatic tratat anterior și își explorează potențialul în liniile anterioare de tratament și în noi setari de cancer de sân.
În cancerul de sân HR pozitiv, AstraZeneca continuă să îmbunătățească rezultatele cu medicamentele de bază Faslodex (fulvestrant) și 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.
Inhibitor PARP Lynparz (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 Lynparz in these settings and to explore its potential in earlier diseases.
Pentru a oferi opțiuni de tratament atât de necesare pacienților cu cancer de sân triplu negativ, o formă agresivă de cancer de sân, AstraZeneca evaluează potențialul datpotamab deruxtecan în monoterapie și în combinație cu imunoterapie rezumat (durvalumab), capivasertib in combination with chemotherapy, and rezumat în combinație cu alte medicamente oncologice, inclusiv Lynparz și deveni mai puternic.
AstraZeneca în oncologie
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 are viziunea de a redefini îngrijirea cancerului și, într-o zi, de a elimina cancerul ca cauză de deces.
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.
Referinte
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 (Engl). 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 Cancer 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 Cancer pulmonar Mutation Consortium. Rac. 2017;1;123(21):4099-4105.
6. Barok M, et al. Trastuzumab emtansine: mechanism of action and drug resistance. Cancer mamar Res. 2014; 16 (2): 209.
7. Nader-Marta G, et al. How we treat patients with metastatic HER2-positive breast cancer. ESMO Open. 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. Lanţetă. 2022 Dec 6;S0140-6736(22)02420-5.
