USFDA ta amince da cututtukan cututtukan cututtukan ciki na hanji Avapritinib (Avapriny, Ayvakit, BLU-285) a ranar 9 ga Janairu, 2020. Magungunan sun ƙunshi alamomi guda biyu: don kula da marasa lafiyar manya tare da raunin rashin aiki ko GIST mai ɗauke da mai karɓar sinadarin ci gaban platelet alpha (PDGFRA) exon 18 maye gurbi (gami da maye gurbin PDGFRA D842V), Da kuma layi huɗu marasa tiyata ko ƙananan marasa lafiya GIST.
ORR yana da girma kamar 86%, Avapritinib yana kawo sabon bege ga marasa lafiya tare da ciwan ciwan ciki na hanji
A watan Nuwamba na 2019, taron shekara-shekara na Haɗin Haɗin Oncology na Haɗin Kai (CTOS) ya ba da sanarwar sakamakon gwajin gwaji na NAVIGATOR Phase I akan avapritinib a cikin PDGFRA ya fitar da sauyin 18 da marasa lafiya da ke karɓar layi na huɗu GIST.
1. Binciken bincike
Ya zuwa Nuwamba 16, 2018, jimillar layin 121 na huɗu da sama da marasa lafiya (galibi maye gurbi na KIT) da kuma 43 GIST marasa lafiya tare da PDGFRA exon 18 maye gurbi an yi rajista. Gwajin ya binciko matakin farko na gwajin a matsayin "400 MG na baka sau ɗaya a rana", kuma daga baya ya rage matakin da aka ba da shawarar zuwa "300 MG na baka sau ɗaya a rana" saboda yawan guba. Mai haƙuri ya karɓi Avapritinib har sai ci gaba da cuta ko cutar da ba za a yarda da ita ba.
2. Ingantaccen bayanan
Ga marasa lafiya tare da maye gurbin PDGFRA exon 18, akwai lokuta 3 na cikakkiyar gafara (OR) da kuma lokuta 34 na remission (PR), kuma ƙimar amsawar haƙiƙa (ORR) shine 86%. Matsakaicin lokacin amsawa (DOR) da rayuwa marar ci gaba (PFS) ba a kai ba. Tun daga ranar yanke bayanan (lokacin bin tsaka-tsaki shine watanni 10.9), 78% na marasa lafiya har yanzu sun amsa.
Daga 111 GIST marasa lafiya tare da layi na huɗu ko sama, 1 yana da cikakkiyar gafartawa, 23 yana da rashi na ƙarshe, ORR ya kasance 22%, tsawon lokacin amsawa na tsakani shine watanni 10.2, PFS na tsakiya ya kasance watanni 3.7, kuma lokacin biyan mediya shine 10.8. wata.
Dangane da aminci, mafi yawan abubuwan da ke faruwa (AEs) galibi sune aji 1, 2 kuma mafi yawanci sune tashin zuciya, kasala, rashin jini, gudawa, amai, da sauransu; maki 3-4 masu dangantaka da AE ≥ 2%, rashin jini, gajiya, ƙarancin Phosphaemia, hyperbilirubinemia, neutropenia da gudawa. 10% na marasa lafiya sun dakatar da magani saboda AEs masu alaƙa da magani.
3. Darajar asibiti
Avapritinib is the first precision therapy approved for GIST patients with PDGFRA exon 18 mutation. It is an oral, potent and selective KIT and PDGFRα inhibitor. Avapritinib has shown extensive inhibition in ciwon ciki na stromal (GIST) with KIT and PDGFRα mutations, including the D842V mutation of the PDGFRα gene and other primary or secondary resistance mutations.
Keyless makullin-PDGFRA exon 18 mutant GIST
Gastrointestinal stromal tumo (GIST) is a rare mesenchymal tissue tumor, accounting for 0.1% to 3% of all gastrointestinal malignant tumors, with an incidence of 1 to 1.5 / 10 million. In people with ciwon ciki na stromal, the most common sites are the stomach and small intestine, but they may also be found anywhere in or near the gastrointestinal tract. If the tumor cannot be completely removed by surgery or the tumor has metastasized, targeted therapy is a standard treatment.
A halin yanzu, har zuwa 85% na ciwace-ciwacen GIST suna da ɗaya daga cikin maye gurbi guda biyu PDGFRA da KIT. Wadannan maye gurbi suna haifar da samar da sinadarai na KIT da PDGFRA marasa kyau, waɗanda ke haifar da ciwon daji. Wadannan sunadaran guda biyu galibi ana iya kashe su ta hanyar imatinib da makamantansu da ke toshe ayyukan furotin. Amma maye gurbin PDGFRA exon 18 na musamman ne, yana canza siffar furotin PDGFRA, don haka yana hana maganin daurinsa. Don maye gurbin PDGFR [exon 18], “maɓalli” na baya bai dace da wannan “kulle ba”.
Avapritinib yana ɗaura PDGFRA da protein na KIT da kyau. A cikin binciken dakin gwaje-gwaje, magani zai iya ɗaure ga duk furotin da aka gwada PDGFRA kuma ya hana aikin su cikin ƙwayoyin kansa.
Magunguna huɗu da aka amince da su a halin yanzu don ciwan ciwan ciki na ciki: Avapritinib, imatinib, sunitinib, da rifaginib. Avapritinib kawai yana ɗaure ne da takamaiman enzymes masu rikitarwa da ake kira kinases (jan da'ira) a cikin ƙwayoyin, yayin da irin waɗannan magunguna ke ɗaure da ƙarin ƙwayoyin cuta. Hotuna: Fasahar Siginar Sel.
| An ba da izinin maganin da aka ƙaddara don ciwon ciwon ciki na ciki (GIST) | Sauran alamomin cutar kansa | Jerin gida |
| Gleevec | Imatinib | Cutar kuturta mai saurin kamuwa da ita (Philadelphia chromosome positive), chronic eosinophilic leukemia, Philadelphia chromosome positive chronic myeloid leukemia, dermatofibrosarcoma protuberans, myeloproliferative tumor | An jera kuma an haɗa su a cikin inshorar likita |
| Regorafenib | Stivarga | Liver cancer, maganin ciwon daji | An jera kuma an haɗa su a cikin inshorar likita |
| Sanarwa | Sunitinib | Xixianai, ciwon daji na koda | An jera kuma an haɗa su a cikin inshorar likita |
| Avapritinib (Ayvakit) | babu | Ba a jera ba |
Sauran ci gaban bincike na cututtukan ciki na ciki
Ripretinib
Ripretinib wani nau'in mai hana kinase II ne wanda zai iya hana maye gurbi na kunnawa a cikin KIT da PDGFRA. Yana da mai hana kinase tare da aikin "sauyawa", wanda zai iya kunna madauki na kunnawa (ko kunna "canzawa") a cikin Tsarin aiki mai aiki, bi da bi, yana hana duk gwajin gwajin KIT da PDGFRA. Tasirin Ripretinib a cikin samfuran kansa na asali da gwajin asibiti na farko kuma sun tabbatar da cewa Ripretinib na iya hana maye gurbin KIT na duniya a cikin marasa lafiya da GIST mai jure wa miyagun ƙwayoyi.
Bayanai daga binciken na III (INVICTUS) ya nuna cewa marasa lafiya da ke karɓar Ripretinib suna da ƙananan haɗarin ci gaban tumo ko mutuwa idan aka kwatanta da placebo, tare da tsaka-tsakin OS na watanni 85, da kuma watanni 15.1 a cikin rukunin wuribo. Late GIST mai layi na huɗu ko magani na sama yana kawo fa'idodi biyu na PFS da OS, kuma Ripretinib yana nuna mafi kyawu.
Larotrectnib
Magungunan farko da aka yi niyya a duniya wanda ba ya rarrabe tushen kumburi don magani na farko-Vitrakvi ® (larotrectinib, wanda ake kira larotinib), ya sami amincewar ƙungiyar tumor ta duniya tun lokacin da aka amince da tallata shi a watan Nuwamba 2018 Doctors da marasa lafiya sun kawo sabon fata da zabi.
The biggest attraction of the drug is that it is a new anti-cancer drug that targets specific gene mutations but not specific cancer types. The NTRK gene fusion solid tumors that it can treat include 17 types of cancers including breast cancer, colorectal cancer, lung cancer, and thyroid ciwon daji, and can be used for both adults and children. NTRK gene fusion exists in 0.7% ~ 3.6% of digestive tract tumors.
Don haka, idan ka yi gwajin kwayoyin halitta, da farko za ka iya ganin ko akwai wasu sauye-sauye da za su iya kawo mu'ujizar rayuwa, za ka iya kiran sashen kiwon lafiya na Global Oncologist Network don fassara rahoton.
Na yi imani da cewa tare da zuwan magunguna da aka yi niyya, marasa lafiya da ciwon ciki
l ciwace-ciwacen daji na iya samun ƙarin zaɓuɓɓukan magani da fa'idodin rayuwa mai tsayi. Ina kuma fatan za a iya jera wadannan magungunan a kasar Sin da wuri-wuri kuma a sanya su cikin inshorar likitanci don amfanin karin marasa lafiya.
