2023 Pébruari: Enhertu (trastuzumab deruxtecan) ti AstraZeneca sareng Daiichi Sankyo geus disatujuan salaku monoterapi pikeun pengobatan penderita sawawa jeung kanker payudara unresectable atanapi métastatik HER2-positip anu geus narima hiji atawa leuwih régimen basis anti-HER2 saméméhna.
Enhertu mangrupikeun konjugat obat antibodi (ADC) anu direkayasa khusus anu diarahkeun ku HER2 anu AstraZeneca sareng Daiichi Sankyo babarengan ngembangkeun sareng komersial.
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 kanker payudara previously treated with trastuzumab and a taxan
Di Cina, kanker payudara mangrupikeun kanker anu paling umum di antawis awéwé, kalayan langkung ti 415,000 kasus diperkirakeun didiagnosis dina taun 2020.
1 Kira-kira 18% tina maotna kanker payudara global lumangsung di Cina dina 2020, kalayan ampir 120,00 maotna disababkeun ku kanker payudara. 1 Kira-kira hiji tina unggal lima kasus kanker payudara HER2-positip. 2
Binghe Xu, MD, Profesor sareng Diréktur Dinas Onkologi Médis, Rumah Sakit Kanker sareng Rumah Sakit Kanker Institut, Akademi Élmu Médis Cina, nyatakeun, "Persetujuan ieu ngagambarkeun tonggak penting pikeun komunitas kanker payudara di China, salaku penderita HER2- kanker payudara métastatik positif terus merlukeun pilihan perlakuan tambahan. Sanajan perlakuan awal, penderita kanker payudara métastatik HER2-positip remen ngalaman progression kasakit, demonstrating pentingna kontrol kasakit sistemik mimiti jeung poténsi Enhertu pikeun mantuan penderita kanker payudara métastatik anu layak pikeun perlakuan.
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, Kapala Daiichi Sankyo's Asia, South and Central America (ASCA) Business Unit, nyatakeun, "Enhertu manjangkeun waktos sateuacan kamajuan panyakit atanapi maot sareng ngabantosan ngarobih deui hasil pikeun pasien anu parantos dirawat kanker payudara métastatik HER2-positip, sareng ayeuna dokter di Cina bakal boga aksés ka ubar penting ieu pikeun penderita maranéhanana. Kalayan persetujuan ieu, Enhertu berpotensi janten standar perawatan anyar di Cina pikeun pasien kanker payudara métastatik HER2-positip dina setting garis kadua.
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 percobaan klinis, 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.
Persetujuan ieu nuturkeun Penetapan Terapi Terobosan NMPA sareng Tinjauan Prioritas Enhertu pikeun jinis kanker payudara ieu dina 2022.
Catetan
Kanker payudara sareng éksprési HER2
Kanker payudara mangrupikeun kanker anu paling umum sareng salah sahiji panyabab utama maotna anu aya hubunganana sareng kanker di dunya.3 Langkung ti dua juta pasien didiagnosis kanker payudara dina 2020, sareng ampir 685,000 maotna sacara global.3 Di Cina, kanker payudara mangrupikeun kanker anu paling umum di awéwé, kalayan langkung ti 415,000 pasien didiagnosis dina taun 2020.1 Aya ampir 120,000 maotna kanker payudara di Cina dina 2020, ngawakilan sakitar 18% tina maotna kanker payudara global.1 Kira-kira hiji tina lima kasus kanker payudara dianggap HER2-positip.2
HER2 mangrupakeun tirosin kinase reséptor pertumbuhan-promosi protéin dinyatakeun dina beungeut loba jenis tumor kaasup payudara, lambung, paru-paru, sarta kanker colorectal. sarta prognosis goréng dina kanker payudara.5
Sanajan perlakuan awal jeung trastuzumab na taxane a, penderita kanker payudara métastatik HER2-positip bakal mindeng ngalaman progression kasakit.6,7
TAKDIR-Dudung03
DESTINY-Breast03 mangrupikeun uji coba global, head-to-head, randomized, open-label, pendaptaran Fase III anu ngevaluasi khasiat sareng kasalametan Enhertu (5.4mg / kg) versus T-DM1 di penderita HER2-positip unresectable jeung / atawa kanker payudara métastatik saméméhna dirawat kalayan trastuzumab na taxane a.
Titik efficacy primér DESTINY-Breast03 nyaéta survival bébas progression (PFS) dumasar kana review sentral bebas buta (BICR). Gemblengna survival (OS) mangrupakeun konci ukuran hasil efficacy sekundér. Titik efficacy sekundér séjén kaasup laju respon obyektif (ORR), lilana respon, PFS dumasar kana assessment investigator jeung kaamanan. Hasil primér tina DESTINY-Breast03 diterbitkeun dina The New England Journal of Medicine,8 kalawan PFS diropéa sarta hasil OS diterbitkeun dina The Lancet.9
DESTINY-Breast03 enrolled 524 patients at multiple sites in Asia, Europe, North America, Oceania and South America.
Enhertu
Enhertu mangrupakeun ADC HER2-diarahkeun. Dirancang nganggo téknologi DXd ADC proprietary Daiichi Sankyo, Enhertu mangrupikeun pimpinan ADC dina portopolio onkologi Daiichi Sankyo sareng program paling canggih dina platform ilmiah ADC AstraZeneca. Enhertu diwangun ku hiji antibodi monoklonal HER2 napel muatan inhibitor topoisomerase I, turunan exatecan, ngaliwatan link cleavable basis tetrapeptide stabil.er.
Enhertu (5.4mg/kg) disatujuan di leuwih ti 40 nagara pikeun pengobatan penderita sawawa jeung kanker payudara HER2-positip unresectable atawa métastatik anu geus narima (atawa hiji atawa leuwih) saméméh regimen basis anti-HER2, boh dina métastatik. setting atawa dina setting neoadjuvant atanapi adjuvant, sarta geus ngembangkeun kambuh panyakit salila atawa dina genep bulan completing terapi dumasar kana hasil tina percobaan DESTINY-Breast03.
Enhertu (5.4mg/kg) disatujuan di leuwih ti 30 nagara pikeun pengobatan penderita sawawa kalawan unresectable atawa métastatik HER2-low (imunohistokimia [IHC] 1+ atawa IHC 2+/in-situ hibridisasi [ISH]-) kanker payudara anu parantos nampi terapi sistemik sateuacana dina setting métastatik atanapi ngembangkeun kambuh panyakit salami atanapi dina genep bulan saatos ngalengkepan kémoterapi adjuvant dumasar kana hasil tina percobaan DESTINY-Breast04.
Enhertu (5.4mg/kg) is approved under accelerated approval in the US for the treatment of adult patients with unresectable or metastatic kanker paru sél non-leutik 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 adénokarsinoma anu nampi regimen dumasar trastuzumab sateuacana dumasar kana hasil tina percobaan DESTINY-Gastric01 sareng / atanapi percobaan DESTINY-Gastric02.
Enhertu program pangwangunan
Program pangwangunan global anu komprehensif dijalankeun pikeun ngevaluasi khasiat sareng kasalametan Enhertu monotherapy across multiple HER2-targetable cancers including breast, gastric, lung and kangker kolorékal. Trials in combination with other anticancer treatments, such as immunotherapy, ogé dijalankeun.
Daiichi Sankyo kolaborasi
Daiichi Sankyo Company, Limited (TSE: 4568) [disebut Daiichi Sankyo] sareng AstraZeneca asup kana kolaborasi global pikeun babarengan ngembangkeun sareng komersialisasi. Enhertu (ADC diarahkeun HER2) dina Maret 2019, sareng datopotamab deruxtecan (DS-1062; ADC anu diarahkeun TROP2) dina Juli 2020, iwal di Jepang dimana Daiichi Sankyo ngajaga hak ekslusif. Daiichi Sankyo tanggung jawab pikeun manufaktur sarta suplai Enhertu sarta datopotamab deruktecan.
AstraZeneca dina kanker payudara
Didorong ku pamahaman anu ngembang ngeunaan biologi kanker payudara, AstraZeneca mimiti tangtangan, sareng ngartikeun deui, paradigma klinis ayeuna ngeunaan kumaha kanker payudara diklasifikasikeun sareng dirawat pikeun nganteurkeun pangobatan anu langkung efektif ka pasien anu peryogi - kalayan ambisi anu wani pikeun ngaleungitkeun hiji dinten. kanker payudara salaku ngabalukarkeun maot.
AstraZeneca gaduh portopolio komprehensif ngeunaan sanyawa anu disatujuan sareng ngajangjikeun dina pangwangunan anu ngungkit mékanisme tindakan anu béda pikeun ngatasi lingkungan tumor kanker payudara anu rupa-rupa sacara biologis.
jeung Enhertu (trastuzumab deruxtecan), ADC anu diarahkeun HER2, AstraZeneca sareng Daiichi Sankyo narékahan pikeun ningkatkeun hasil dina kanker payudara métastatik métastatik HER2-positip sareng HER2-rendah anu dirawat sateuacana sareng ngajalajah poténsialna dina jalur perawatan sateuacana sareng dina setélan kanker payudara énggal.
Dina kanker payudara HR-positip, AstraZeneca terus ningkatkeun hasil sareng obat dasar Faslodex (fulvestrant) jeung Zoladex (goserelin) sarta boga tujuan pikeun reshape spasi HR-positip kalawan SERD generasi saterusna sarta poténsi camizestrant ubar anyar, kitu ogé poténsi munggaran-di-kelas AKT inhibitor kinase, capivasertib. AstraZeneca ogé kolaborasi sareng Daiichi Sankyo pikeun ngajalajah poténsi ADC anu diarahkeun TROP2, datopotamab deruxtecan, dina setting ieu.
Sambetan PARP Lynparza (olaparib) mangrupikeun pilihan pengobatan anu ditujukeun anu parantos ditaliti dina penderita kanker payudara awal sareng métastatik kalayan mutasi BRCA anu diwariskeun. AstraZeneca jeung MSD (Merck & Co., Inc. di AS jeung Kanada) terus panalungtikan Lynparza dina setélan ieu sareng ngajalajah poténsina dina panyakit anu baheula.
Pikeun nyangking pilihan perawatan anu diperyogikeun pikeun penderita kanker payudara triple-négatip, bentuk agrésif kanker payudara, AstraZeneca ngevaluasi poténsi datopotamab deruxtecan nyalira sareng digabungkeun sareng immunotherapy. Imfinzi (durvalumab), capivasertib dina kombinasi kalayan kémoterapi, jeung Imfinzi digabungkeun sareng obat onkologi anu sanés, kalebet Lynparza jeung Enhertu.
AstraZeneca dina Onkologi
AstraZeneca nuju revolusi onkologi kalayan ambisi pikeun nyayogikeun pangobatan pikeun kanker dina unggal bentuk, nuturkeun élmu pikeun ngartos kanker sareng sagala pajeulitna pikeun mendakan, ngembangkeun, sareng nganteurkeun obat anu ngarobih kahirupan ka pasien.
Fokus perusahaan nyaéta kana sababaraha kanker anu paling nangtang. Ngaliwatan inovasi pengkuh yén AstraZeneca parantos ngawangun salah sahiji portofolio sareng pipa anu paling beragam di industri, kalayan poténsial pikeun ngatalisan parobahan dina prakték kadokteran sareng ngarobih pangalaman pasien.
AstraZeneca gaduh visi pikeun ngartikeun ulang perawatan kanker sareng, hiji dinten, ngaleungitkeun kanker salaku panyabab maot.
AstraZeneca
AstraZeneca (LSE / STO / Nasdaq: AZN) mangrupikeun perusahaan biofarmaseutik global anu dipimpin ku élmu anu museurkeun kana panemuan, pamekaran, sareng komersialisasi obat resep dina Onkologi, Panyakit Langka, sareng BioPharmaceuticals, kalebet Cardiovascular, Renal & Metabolism, sareng Pernafasan. & Imunologi. Dumasar di Cambridge, Inggris, AstraZeneca beroperasi di langkung ti 100 nagara, sareng obat-obatan inovatifna dianggo ku jutaan pasien di sakuliah dunya.
Rujukan
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2. Ahn S, dkk. Status HER2 dina kanker payudara: parobahan dina tungtunan sareng faktor complicating pikeun interpretasi. J Pathol Transl Med. 2020; 54(1): 34-44.
3. Sung H, dkk. Statistik Kanker Global 2020: Perkiraan Kajadian sareng Kematian GLOBOCAN Di sakuliah dunya pikeun 36 Kanker di 185 Nagara. CA Kangker J Clin. 2021; 10.3322/caac.21660.
4. Iqbal N, dkk. Reséptor Faktor Tumuwuh épidermal manusa 2 (HER2) dina Kangker: Overexpression sareng Implikasi Terapi. Mol Biol Int. 2014; 852748.
5. Pillai R, et al. HER2 mutations in lung adenocarcinomas: A report from the Kangker paru Mutation Consortium. kangker. 2017;1;123(21):4099-4105.
6. Barok M, dkk. Trastuzumab emtansine: mékanisme aksi sareng résistansi ubar. Kanker payudara Res. 2014; 16 (2): 209.
7. Nader-Marta G, et al. Kumaha urang ngubaran penderita kanker payudara métastatik HER2-positip. ESMO Buka. 2022; 7:1.
8. Cortes J, dkk. Trastuzumab Deruxtecan versus Trastuzumab Emtansine pikeun Kangker Payudara. N Engl J Med. 2022; 386: 1143-1154.
9. Hurvitz S, dkk. Trastuzumab deruxtecan versus trastuzumab emtansine di penderita kanker payudara métastatik HER2-positip: hasil diropéa tina DESTINY-Breast03, a randomised, buka-labél, fase 3 sidang. Lancet. 2022 Dec 6;S0140-6736(22)02420-5.
