Febhuwari 2023: I-Enhertu (trastuzumab deruxtecan) evela kwa-AstraZeneca kanye no-Daiichi Sankyo igunyazwe njenge-monotherapy yokwelashwa kweziguli ezikhulile ezinomdlavuza webele we-HER2 ongenayo i-metastatic noma i-metastatic ezithole uhlobo olulodwa noma ngaphezulu olususelwe ekulweni ne-HER2.
I-Enhertu iyi-antibody conjugate (ADC) eyakhelwe ngokukhethekile i-HER2 eqondiswe ngqo i-AstraZeneca kanye noDaiichi Sankyo ngokuhlanganyela abayithuthukisayo futhi bayayidayisa.
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 umdlavuza webele previously treated with trastuzumab and a taxan
E-China, umdlavuza webele ungumdlavuza odlange kakhulu kwabesifazane, njengoba kulindeleke ukuthi kutholakale amacala angaphezu kuka-415,000 ngo-2020.
1 Cishe i-18% yokufa komdlavuza webele emhlabeni wonke kwenzeka eChina ngo-2020, futhi kwafa cishe i-120,00 ngenxa yomdlavuza webele. 1 Cishe isigameko esisodwa kwezinhlanu zomdlavuza webele sine-HER2-positive. 2
UBinghe Xu, MD, uSolwazi kanye noMqondisi woMnyango Wezempilo, Isibhedlela Somdlavuza kanye Nesibhedlela Somdlavuza, iChinese Academy of Medical Science, uthe, "Le mvume imele ingqophamlando emphakathini womdlavuza webele eChina, njengeziguli ezine-HER2- umdlavuza webele we-metastatic omuhle uyaqhubeka nokudinga izindlela zokwelashwa ezengeziwe. Naphezu kokwelashwa kokuqala, iziguli ezinomdlavuza webele we-HER2-positive metastatic zivame ukubhekana nokukhula kwesifo, okubonisa ukubaluleka kokulawulwa kwezifo ngokushesha kanye nethuba le-Enhertu lokusiza iziguli ezinomdlavuza webele we-metastatic ezifanele ukuthola ukwelashwa.”
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.
UKiminori Nagao, oyiNhloko yeDaiichi Sankyo's Asia, South and Central America (ASCA) Business Unit, uthe, "I-Enhertu yelula isikhathi ngaphambi kokuqhubekela phambili kwesifo noma ukufa futhi isiza ukuchaza kabusha imiphumela yeziguli ezinomdlavuza webele webele owelashwe ngaphambilini i-HER2-positive metastatic, kanye manje odokotela baseShayina bazokwazi ukuthola lo muthi obalulekile ezigulini zabo. Ngale mvume, i-Enhertu inethuba lokuba izinga elisha lokunakekela e-China ezigulini ezinomdlavuza webele we-HER2-positive metastatic esimweni somugqa wesibili.”
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 izivivinyo zokwelashwa, 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.
Lokhu kugunyazwa kulandela Ukuqokwa Kwe-NMPA Yase-China Nokubuyekezwa Okubalulekile Kwe-Enhertu yalolu hlobo lomdlavuza webele ngo-2022.
amanothi
Umdlavuza webele kanye ne-HER2 expression
Umdlavuza webele umdlavuza ovame kakhulu futhi ungenye yezimbangela ezihamba phambili zokufa kwabantu okuhlobene nomdlavuza emhlabeni jikelele.3 Iziguli ezingaphezu kwezigidi ezimbili kwatholakala ukuthi zinomdlavuza webele ngo-2020, nokufa kwabantu abacishe babe ngu-685,000 emhlabeni jikelele.3 E-China, umdlavuza webele uwumdlavuza ovame kakhulu kwabesifazane, njengoba kutholakale iziguli ezingaphezu kuka-415,000 ngo-2020.1 Cishe bangu-120,000 abantu ababulawa umdlavuza webele eChina ngo-2020, okusho ukuthi cishe i-18% yabantu ababulawa umdlavuza webele emhlabeni wonke.1 Cishe isigameko esisodwa kwezihlanu zomdlavuza webele sithathwa njenge-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
Ngaphandle kokwelashwa kokuqala nge-trastuzumab kanye ne-taxane, iziguli ezinomdlavuza webele we-HER2-positive metastatic ngokuvamile zizobhekana nokukhula kwesifo.6,7
I-DESTINY-Breast03
I-DESTINY-Breast03 iyisivivinyo somhlaba wonke, esibheka phezulu, esingahleliwe, esivulekile, sokubhalisa seSigaba III esihlola ukusebenza kahle nokuphepha kwe. I-Enhertu (5.4mg/kg) uma kuqhathaniswa ne-T-DM1 ezigulini ezinomdlavuza webele we-HER2 ongenakunqandeka kanye/noma we-metastatic owelashwe ngaphambilini nge-trastuzumab ne-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 I-New England Journal of Medicine,8 ngemiphumela ebuyekeziwe ye-PFS ne-OS eshicilelwe ku I-Lancet.9
DESTINY-Breast03 enrolled 524 patients at multiple sites in Asia, Europe, North America, Oceania and South America.
Enhertu
I-Enhertu iyi-ADC eqondiswe yi-HER2. Idizayinelwe kusetshenziswa ubuchwepheshe be-DXd ADC yobunikazi be-Daiichi Sankyo, i-Enhertu iyi-ADC ehamba phambili kuphothifoliyo ye-oncology ye-Daiichi Sankyo kanye nohlelo oluthuthuke kakhulu kunkundla yesayensi ye-AstraZeneca ye-ADC. I-Enhertu iqukethe i-HER2 monoclonal antibody exhunywe ku-topoisomerase I inhibitor payload, i-exatecan derivative, ngesixhumanisi esivulekayo esisekelwe ku-tetrapeptidest.
I-Enhertu (5.4mg/kg) ivunyelwe emazweni angaphezu kwama-40 ukuze zelashwe iziguli ezikhulile ezinomdlavuza webele we-HER2-positive ongasuleki noma one-metastatic ezithole (noma eyodwa noma ngaphezulu) irejimeni esekelwe ngaphambili yokulwa ne-HER2, kungaba ku-metastatic. ukusetha noma ku-neoadjuvant noma i-adjuvant setting, futhi baye bahlakulela ukuphindaphinda kwesifo phakathi noma phakathi nezinyanga eziyisithupha zokuqeda ukwelashwa ngokusekelwe emiphumeleni yocwaningo lwe-DESTINY-Breast03.
I-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.
I-Enhertu (5.4mg/kg) is approved under accelerated approval in the US for the treatment of adult patients with unresectable or metastatic umdlavuza wamaphaphu weselula ongewona omncane 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.
I-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 i-adenocarcinoma abathole uhlobo lwangaphambili olususelwe ku-trastuzumab ngokusekelwe emiphumeleni yokuhlola ye-DESTINY-Gastric01 kanye/noma nokuhlola kwe-DESTINY-Gastric02.
I-Enhertu uhlelo lokuthuthukisa
Uhlelo oluphelele lwentuthuko yomhlaba wonke luyaqhubeka oluhlola ukusebenza kahle nokuphepha kwe I-Enhertu monotherapy across multiple HER2-targetable cancers including breast, gastric, lung and umdlavuza omhlophe. Trials in combination with other anticancer treatments, such as immunotherapy, nazo ziyaqhubeka.
Ukubambisana kwe-Daiichi Sankyo
I-Daiichi Sankyo Company, Limited (TSE: 4568) [ebizwa ngokuthi i-Daiichi Sankyo] kanye ne-AstraZeneca bangene ekusebenzisaneni komhlaba wonke ukuze bathuthukise ngokuhlanganyela futhi bahwebe. I-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 I-Enhertu kanye ne-datopotamab deruxtecan.
I-AstraZeneca kumdlavuza webele
Iqhutshwa ukuqonda okukhulayo kwebhayoloji yomdlavuza webele, i-AstraZeneca isiqala ukubekela inselele, futhi ichaza kabusha, ipharadigm yamanje yomtholampilo yokuthi umdlavuza webele uhlukaniswa kanjani futhi welashwe ukuze ulethe ukwelashwa okuphumelelayo nakakhulu ezigulini ezidingayo - ngesifiso esinesibindi sokuqeda usuku olulodwa. umdlavuza webele njengembangela yokufa.
I-AstraZeneca inephothifoliyo ebanzi yezinhlanganisela ezivunyiwe nezithembisayo ekuthuthukisweni ezisebenzisa izindlela ezahlukahlukene zokwenza ukubhekana nemvelo ehlukahlukene yesimila somdlavuza webele.
With I-Enhertu (trastuzumab deruxtecan), i-ADC eqondiswe ku-HER2, i-AstraZeneca kanye noDaiichi Sankyo bahlose ukuthuthukisa imiphumela yokwelashwa kwangaphambilini komdlavuza webele we-HER2-positive kanye ne-HER2-low metastatic futhi bahlola amandla awo emigqeni yangaphambili yokwelashwa nasezilungiselelweni ezintsha zomdlavuza webele.
Kumdlavuza webele we-HR-positive, i-AstraZeneca iyaqhubeka nokwenza ngcono imiphumela ngemithi eyisisekelo I-Faslodex (i-fulvestrant) kanye 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.
I-PARP inhibitor I-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 I-Lynparza in these settings and to explore its potential in earlier diseases.
Ukuletha izinketho zokwelashwa ezidingeka kakhulu ezigulini ezinomdlavuza webele ophindwe kathathu, uhlobo olunolaka lomdlavuza webele, i-AstraZeneca ihlola amandla e-datopotamab deruxtecan kuphela futhi ihlanganiswe ne-immunotherapy. Imfinzi (durvalumab), i-caivasertib ehlanganiswe ne-chemotherapy, kanye Imfinzi ngokuhlanganiswa neminye imithi ye-oncology, kuhlanganise I-Lynparza futhi I-Enhertu.
I-AstraZeneca ku-oncology
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.
I-AstraZeneca inombono wokuchaza kabusha ukunakekelwa komdlavuza futhi, ngolunye usuku, iqede umdlavuza njengembangela yokufa.
I-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.
Okubhekwayo
1. Wei Cao, et al. Ukushintsha amaphrofayili omthwalo womdlavuza emhlabeni wonke naseChina: ukuhlaziya kwesibili kwezibalo zomdlavuza zomhlaba wonke 2020. U-Chin Med J (Engl). 2021 Ephreli 5; 134(7): 783–791.
2. U-Ahn S, nabanye. Isimo se-HER2 kumdlavuza webele: izinguquko eziqondisweni nezici eziyinkimbinkimbi zokuchazwa. J Pathol Transl Med. 2020; 54(1): 34-44.
3. Sung H, et al. Izibalo Zomdlavuza Zomhlaba Wonke 2020: Izilinganiso Ze-GLOBOCAN Zezehlakalo Nokufa Emhlabeni Wonke KwamaCancer angama-36 Emazweni ayi-185. I-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. I-Mol Biol Int. 2014; 852748.
5. Pillai R, et al. HER2 mutations in lung adenocarcinomas: A report from the Lung Cancer Mutation Consortium. Cancer. 2017;1;123(21):4099-4105.
6. Barok M, et al. I-Trastuzumab emtansine: indlela yokusebenza kanye nokumelana nezidakamizwa. Breast Cancer Res. 2014; 16 (2): 209.
7. U-Nader-Marta G, et al. Siziphatha kanjani iziguli ezinomdlavuza webele we-metastatic HER2-positive. ESMO Vula. 2022; 7:1.
8. Cortes J, et al. Trastuzumab Deruxtecan vs Trastuzumab Emtansine for Breast Cancer. N Engl J Med. I-2022; I-386: 1143-1154.
9. U-Hurvitz S, et al. I-Trastuzumab deruxtecan iqhathaniswa ne-trastuzumab emtansine ezigulini ezinomdlavuza webele we-metastatic we-HER2-positive: imiphumela ebuyekeziwe evela ku-DESTINY-Breast03, ilebula engahleliwe, evulekile, isilingo sesigaba sesi-3. I-Lancet. 2022 Dec 6;S0140-6736(22)02420-5.
