Seattle Jenetik 'HER2 vize TKI Oral Dwog Tukysa te apwouve pa Inyon Ewopeyen an!

Seattle Genetik (Seagen) denyeman te anonse ke Komisyon Ewopeyen an (EC) te apwouve vize antikristyanism dwog la Tukysa (tucatinib), konbine avek trastuzumab ak kapesitabin, pou tretman an nan HER2 ki te deja resevwa omwen de rekomandasyon anti-HER2. Pasyan granmoun ki gen kanse pozitif lokalman avanse oswa metastatik kanse nan tete.

Tukysa se yon ti molekil ti kras molekil kinaz inibitor (TKI) ki sib HER2, yon pwoteyin ki ankouraje kwasans lan nan selil kanse. Apwobasyon sa a aplike a tout eta manm nan Inyon Ewopeyen an kom byen ke Novej, Liechtenstein, Islann ak Northern Ireland. Ozetazini, Tukysa te apwouve pa FDA nan mwa avril 2020 pou tretman pasyan ki gen avanse oswa metastatik HER2-pozitif kanse nan tete ki pa ka chirijikal retire e ki te deja resevwa youn oswa plis anti-HER2 rejim pou maladi metastatik, ki gen ladan devlopman nan sevo. Pasyan ki te transfere. Anplis de sa, Tukysa te tou te apwouve nan Kanada, Swis, Singapore, ak Ostrali.

Apwobasyon Inyon Ewopeyen an se yon gwo avansman pou pasyan Ewopeyen yo. Yo pral resevwa yon medikaman ki apwouve pou premye fwa, ki se konfime yo dwe efikas nan HER2-pozitif pasyan kanse nan tete ki te pwogrese apre li fin resevwa de estanda anti-HER2 rekomandasyon. Bay benefis sivivan. Nan jijman an pivotal HER2CLIMB, konpare ak trastuzumab + kapestab tretman, Tukysa + trastuzumab + kapesitab tretman rejim amelyore siviv an jeneral (OS) ak pwogresyon-gratis siviv pasyan (PFS), ki gen ladan pasyan ki gen aktif, trete, oswa metastas nan sevo avanse ki gen bezwen yo kleman inmet.

Dokte Clay Siegall, CEO nan Seagen, te di: "Tukysa konbinezon terapi se yon tretman landmark pou pasyan ki gen KAnse tete METASTATIK HER2-pozitif (avek oswa san metastases nan sevo). Sivivan an jeneral nan pasyan yo te siyifikativman pwolonje. Nou kontan ke Tukysa te kounye a apwouve nan Ewop, epi nou gade pou pi devan pou bay Tukysa nan pasyan pi vit ke posib."

Apwobasyon sa a baze sou done ki soti nan jijman an pivote HER2CLIMB klinik. Sa a se yon jijman owaza (2:1), doub-aveg, plasbo-kontwole, pozitif-dwog-kontwole jijman nan pasyan ki gen kanse lokalman avanse oswa metastatik HER2-pozitif, konbine tucatinib ak trastuzumab ak carbohydrate rejim konbinezon an nan pecitabine te konpare ak konbinezon an konbinezon nan trastuzumab ak capecitabine. Pasyan yo enskri nan jijman an te deja resevwa trastuzumab, pertuzumab, ak T-DM1 (ado-trastuzumab emtansine) tretman, ak 48% nan pasyan yo te gen metastas nan sevo le yo te enskri nan etid la.

Rezilta yo te montre ke jijman an rive nan pwen prensipal la nan siviv pwogre-gratis (PFS): konpare ak trastuzumab + kapesitabin rkomande, tucatinib + trastuzumab + kapesitabin rejim te montre pi bon efikasite, risk pou yo pwogresyon maladi oswa lanmo te siyifikativman redwi pa 46% (medyan PFS: 7.8 mwa vs 5.6 mwa; HR = 0.54 [95% CI: 0.42-0.71], p<0.00001). in="" the="" interim="" analysis,="" the="" trial="" also="" reached="" two="" key="" secondary="" endpoints.="" compared="" with="" the="" trastuzumab="" +="" capecitabine="" treatment="" group,="" the="" overall="" survival="" (os)="" of="" the="" tucatinib="" +="" trastuzumab="" +="" capecitabine="" treatment="" group="" improved="" (median="" os:="" 21.9="" months="" vs="" 17.4="" month),="" the="" risk="" of="" death="" was="" reduced="" by="" 34%="" (hr="0.66" [95%ci:="" 0.50-0.88],="" p="0.0048)," and="" the="" objective="" remission="" rate="" was="" nearly="" doubled="" (orr:="" 40.6%="" vs="" 22.8%).="" for="" patients="" with="" brain="" metastases="" at="" baseline,="" compared="" with="" the="" trastuzumab+capecitabine="" regimen,="" the="" tucatinib+trastuzumab+capecitabine="" regimen="" also="" showed="" superior="" pfs="" data="" (median="" pfs:="" 7.6="" month="" vs.="" 5.4="" months),="" the="" risk="" of="" disease="" progression="" or="" death="" was="" significantly="" reduced="" by="" 52%="" (hr="0.48[95%CI:0.34-0.69],"><>

Nan jijman sa a, sekirite a nan tucatinib konbine avek trastuzumab ak capecitabine se yon bon bagay. Reyaksyon yo pi komen piblisite nan gwoup la tretman tucatinib enkli dyare, wouj sansasyon palmoplantar (PPE), ke plen, fatig, ak vomi. Konpare ak gwoup la kontwol, evenman negatif nan 3e ane oswa pi wo a nan gwoup la tretman tucatinib enkli dyare (12.9% vs 8.6%), elve aminotransferaz aspatat (AST) (4.5% vs 0.5%), alanine aminotransferase (ALT) ) Ogmante (5.4% vs 0.5%) ak bilirubin ogmante (0.7% vs 2.5%). Pa gen medikaman prevantif antidiarheal nesese. Evenman kontwol ki mennen nan discontinuation te estraodine nan gwoup la tucatinib ak gwoup la kontwol (5.7% ak 3.0, respektivman).

HER2 se yon récepteurs kwasans ki se overexpressed nan yon varyete kanse, ki gen ladan kanse nan tete, kanse kolorek, ak kanse nan gastric. HER2 medyate kwasans selile, diferansyasyon ak siviv. Nan kanse nan tete, apepre 15-20% se HER2 pozitif. Konpare ak KAnse nan tete HER2-negatif, KAnse nan tete HER2-pozitif se pi agresif ak pi fasil pou rplonje. Jiska 50% nan pasyan ki gen metastatik HER2-pozitif kanse nan tete devlope metastas nan sevo sou tan.

Engredyan an aktif pharmaceutiical nan Tukysa se tukysa, ki se yon oral byolojik efikas tirosin kinaz entedi (TKI) ki se tre selektif pou HER2 e pa gen okenn efe inibitory evidan sou EGFR. Anpeche EGFR ki asosye ak toksisite enpotan, ki gen ladan gratel sou po ak dyare. Tucatinib te montre aktivite ki ka geri tankou yon dwog sel, konbinezon chimyoterapi ak lot HER2 vize dwog (tankou trastuzumab). Etid klinik sou konbinezon an nan tucatinib te montre sistemik ak anti-nan sevo metastasi aktivite. Pwemyeman, tucatinib te akode deziyasyon dwog ofelen pa FDA a pou tretman nan pasyan kanse nan tete ak metastas nan sevo.

Anplis jijman AN HER2CLIMB, Seattle Genetik ap fe yon lot faz III jijman nan klinik, HER2CLIMB-02, evalye konbinezon an nan tucatinib ak T-DM1 ak T-DM1 rejyon sel-ajan pou tretman an nan kanse lokalman avanse oswa metastatik HER2 pozitif kanse nan tete. Anplis de sa, konpayi an se tou fe yon faz II klinik jijman MONTAINEER evalye tucatinib konbine avek trastuzumab nan tretman an nan HER2-pozitif, RAS sovaj-kalite, metastatik oswa enkwayab kanse kolorek.