2023-fevral: AstraZeneca va Daiichi Sankyo'dan Enhertu (trastuzumab deruxtecan) bir yoki bir nechta oldingi HER2-ga asoslangan rejimlarni olgan, rezektsiya qilib bo'lmaydigan yoki metastatik HER2-musbat ko'krak saratoni bilan og'rigan katta yoshli bemorlarni davolash uchun monoterapiya sifatida tasdiqlangan.
Enhertu, AstraZeneca va Daiichi Sankyo birgalikda ishlab chiqayotgan va tijoratlashtirayotgan maxsus ishlab chiqilgan HER2-yo'naltirilgan antikor dori konjugati (ADC).
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 ko'krak saratoni previously treated with trastuzumab and a taxan
Xitoyda ko'krak bezi saratoni ayollar orasida eng ko'p tarqalgan saraton bo'lib, 415,000 yilda 2020 XNUMX dan ortiq kasallik aniqlanishi kutilmoqda.
1 18 yilda ko'krak bezi saratoni bilan bog'liq global o'limning taxminan 2020% Xitoyda sodir bo'lgan, 120,00 ga yaqin o'lim ko'krak saratoni bilan bog'liq. 1 Ko'krak bezi saratonining taxminan har beshtasidan biri HER2-musbat. 2
Binghe Xu, tibbiyot fanlari doktori, professor va Xitoy Tibbiyot fanlari akademiyasi Tibbiy onkologiya, saraton kasalxonasi va institut saraton kasalxonasi bo'limi direktori, shunday dedi: "Ushbu tasdiqlash HER2- bilan kasallangan Xitoyda ko'krak bezi saratoni hamjamiyati uchun muhim bosqichdir. ijobiy metastatik ko'krak saratoni qo'shimcha davolash usullarini talab qiladi. Dastlabki davolanishga qaramay, HER2-musbat metastatik ko'krak saratoni bilan og'rigan bemorlar tez-tez kasallikning rivojlanishini boshdan kechirishadi, bu kasallikni erta tizimli nazorat qilish muhimligini va Enhertu-ning davolanishga yaroqli metastatik ko'krak saratoni bilan kasallangan bemorlarga yordam berish potentsialini ko'rsatadi.
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, Daiichi Sankyoning Osiyo, Janubiy va Markaziy Amerika (ASCA) biznes bo'limi rahbari, "Enhertu kasallikning rivojlanishi yoki o'limidan oldingi vaqtni uzaytiradi va ilgari HER2-musbat metastatik ko'krak saratoni bilan davolangan bemorlarning natijalarini qayta aniqlashga yordam beradi va va endi Xitoydagi shifokorlar o'z bemorlari uchun ushbu muhim doridan foydalanish imkoniyatiga ega bo'ladilar. Ushbu tasdiqlash bilan Enhertu ikkinchi qatorda HER2-musbat metastatik ko'krak saratoni bilan og'rigan bemorlar uchun Xitoyda yangi tibbiy yordam standartiga aylanish potentsialiga ega.
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 klinik tadqiqotlar, 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.
Ushbu tasdiq Xitoyning NMPA tomonidan 2022 yilda ushbu turdagi ko'krak bezi saratoni uchun Enhertu-ning yutuq terapiyasi va ustuvorliklarini ko'rib chiqishdan keyin berilgan.
Eslatmalar
Ko'krak saratoni va HER2 ifodasi
Ko'krak saratoni eng keng tarqalgan saraton va butun dunyo bo'ylab saraton bilan bog'liq o'limning asosiy sabablaridan biridir.3 2020 yilda ikki milliondan ortiq bemorga ko'krak bezi saratoni tashxisi qo'yilgan, dunyo bo'ylab qariyb 685,000 XNUMX kishi vafot etgan.3 Xitoyda ko'krak saratoni ayollarda eng ko'p uchraydigan saraton bo'lib, 415,000 yilda 2020 XNUMX dan ortiq bemorga tashxis qo'yilgan.1 120,000 yilda Xitoyda ko'krak bezi saratonidan 2020 18 ga yaqin o'lim qayd etilgan, bu global ko'krak bezi saratonidan o'limning taxminan XNUMX foizini tashkil qiladi.1 Taxminan har beshinchi ko'krak bezi saratoni holati HER2-musbat hisoblanadi.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
Trastuzumab va taksan bilan dastlabki davolanishga qaramay, HER2-musbat metastatik ko'krak saratoni bilan og'rigan bemorlarda ko'pincha kasallikning rivojlanishi kuzatiladi.6,7
TAQDIR-Ko'krak03
DESTINY-Breast03 - bu global, boshma-qarshi, tasodifiy, ochiq yorliqli, ro'yxatdan o'tish III bosqichining samaradorligi va xavfsizligini baholaydigan sinov. kuchliroq bo'ling Oldin trastuzumab va taksan bilan davolangan HER5.4-musbat rezektsiya qilinmagan va/yoki metastatik ko'krak saratoni bo'lgan bemorlarda T-DM1ga nisbatan (2 mg/kg).
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 tibbiyot jurnali,8 da chop etilgan yangilangan PFS va OS natijalari bilan Lancet.9
DESTINY-Breast03 enrolled 524 patients at multiple sites in Asia, Europe, North America, Oceania and South America.
Enhertu
kuchliroq bo'ling HER2 tomonidan boshqariladigan ADC hisoblanadi. Daiichi Sankyo kompaniyasining xususiy DXd ADC texnologiyasidan foydalangan holda ishlab chiqilgan Enhertu Daiichi Sankyo onkologiya portfelidagi yetakchi ADC va AstraZeneca ADC ilmiy platformasidagi eng ilg‘or dastur hisoblanadi. kuchliroq bo'ling barqaror tetrapeptidga asoslangan ajraladigan havola orqali topoizomeraz I inhibitori foydali yukiga, eksatekan hosilasiga biriktirilgan HER2 monoklonal antikoridan iborat.ar.
kuchliroq bo'ling (5.4 mg/kg) 40 dan ortiq mamlakatlarda rezektsiya qilib bo'lmaydigan yoki metastatik HER2-musbat ko'krak bezi saratoni bilan og'rigan kattalar bemorlarini (yoki bir yoki undan ko'p) ilgari HER2-ga qarshi metastatik rejimda davolash uchun tasdiqlangan. DESTINY-Breast03 sinovi natijalariga ko'ra, neoadjuvant yoki adjuvant sharoitda va terapiya tugaganidan keyin olti oy davomida yoki kasallikning qaytalanishi rivojlandi.
kuchliroq bo'ling (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.
kuchliroq bo'ling (5.4mg/kg) is approved under accelerated approval in the US for the treatment of adult patients with unresectable or metastatic kichik hujayrali o'pka saratoni 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.
kuchliroq bo'ling (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 adenokarsinoma DESTINY-Gastric01 va/yoki DESTINY-Gastric02 sinovlari natijalariga ko'ra, oldingi trastuzumabga asoslangan rejimni olganlar.
kuchliroq bo'ling rivojlantirish dasturi
Samaradorlik va xavfsizligini baholash uchun keng qamrovli global rivojlanish dasturi amalga oshirilmoqda kuchliroq bo'ling monotherapy across multiple HER2-targetable cancers including breast, gastric, lung and kolorektal saraton. Trials in combination with other anticancer treatments, such as immunoterapiya, ham olib borilmoqda.
Daiichi Sankyo hamkorligi
Daiichi Sankyo Company, Limited (TSE: 4568) [Daiichi Sankyo deb ataladi] va AstraZeneca birgalikda ishlab chiqish va tijoratlashtirish uchun global hamkorlikka kirishdilar. kuchliroq bo'ling (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 kuchliroq bo'ling va datopotamab deruxtekan.
Ko'krak saratonida AstraZeneca
AstraZeneca ko'krak bezi saratoni biologiyasi bo'yicha o'sib borayotgan tushunchaga asoslanib, muhtoj bemorlarga yanada samaraliroq davolash usullarini taqdim etish uchun ko'krak bezi saratoni qanday tasniflanishi va davolashning hozirgi klinik paradigmasini shubha ostiga qo'yadi va qayta ta'riflaydi - bir kun uni yo'q qilishga dadil intilish. ko'krak saratoni o'lim sababi sifatida.
AstraZeneca ishlab chiqilayotgan tasdiqlangan va istiqbolli birikmalarning keng qamrovli portfeliga ega bo'lib, ular biologik xilma-xil ko'krak bezi saratoni o'smalari muhitini hal qilish uchun turli ta'sir mexanizmlaridan foydalanadi.
bilan kuchliroq bo'ling (trastuzumab deruxtecan), HER2-yo'naltirilgan ADC, AstraZeneca va Daiichi Sankyo ilgari davolangan HER2-musbat va HER2-past metastatik ko'krak saratoni natijalarini yaxshilashga intilmoqda va uning potentsialini davolashning oldingi bosqichlarida va yangi ko'krak saratoni sharoitlarida o'rganmoqda.
HR-musbat ko'krak saratonida AstraZeneca asosiy dorilar yordamida natijalarni yaxshilashda davom etmoqda. Faslodeks (fulvestrant) va 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 inhibitori Linparza (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 Linparza in these settings and to explore its potential in earlier diseases.
Ko'krak bezi saratonining agressiv shakli bo'lgan uch salbiy ko'krak bezi saratoni bilan og'rigan bemorlarga juda zarur bo'lgan davolash usullarini taqdim etish uchun AstraZeneca datopotamab deruxtekanning yakka o'zi va immunoterapiya bilan birgalikda potentsialini baholaydi. Xulosa (durvalumab), kapivasertib kemoterapi bilan birgalikda va Xulosa boshqa onkologik dorilar bilan birgalikda, shu jumladan Linparza va kuchliroq bo'ling.
Onkologiyada AstraZeneca
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 saraton kasalligini davolashni qayta belgilash va bir kun kelib saratonni o'lim sababi sifatida yo'q qilish nuqtai nazariga ega.
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.
Manbalar
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2. Ahn S va boshqalar. Ko'krak bezi saratonidagi HER2 holati: ko'rsatmalardagi o'zgarishlar va talqin qilish uchun murakkablashtiruvchi omillar. J Pathol Transl Med. 2020; 54(1): 34-44.
3. Sung H va boshqalar. Global saraton statistikasi 2020: GLOBOCAN hisob-kitoblari bo'yicha dunyo bo'ylab 36 ta mamlakatda 185 ta saraton kasalligiga chalinish va o'lim darajasi. CA saraton 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 yil; 852748.
5. Pillai R, et al. HER2 mutations in lung adenocarcinomas: A report from the O'pka saratoni Mutation Consortium. rak. 2017;1;123(21):4099-4105.
6. Barok M va boshqalar. Trastuzumab emtansin: ta'sir mexanizmi va dori qarshiligi. Ko'krak bezi saratoni Res. 2014 yil; 16 (2): 209 yil.
7. Nader-Marta G va boshqalar. Biz metastatik HER2-musbat ko'krak saratoni bilan og'rigan bemorlarni qanday davolashamiz. ESMO ochiq. 2022; 7:1.
8. Kortes J va boshqalar. Ko'krak bezi saratoni uchun Trastuzumab Deruxtecan va Trastuzumab Emtansine. N Engl J Med. 2022; 386: 1143-1154.
9. Hurvitz S va boshqalar. HER2-musbat metastatik ko'krak saratoni bilan og'rigan bemorlarda trastuzumab deruxtekan va trastuzumab emtansin: DESTINY-Breast03 dan yangilangan natijalar, randomizatsiyalangan, ochiq etiketli, 3-bosqich sinovi. Lancet. 2022 Dec 6;S0140-6736(22)02420-5.
