Burooyinka caloosha ku dhaca ee caloosha bartilmaameedsada daroogada Avapritinib (Avapriny, Ayvakit, BLU-285) waxaa ansixiyay USFDA 9th Janaayo, 2020. Daawada waxay daboolaysaa laba tilmaamood: daaweynta bukaanka qaangaarka ah ee qalliinka aan la shaqeyn karin ama GIST metastatic ee xambaarsan soo-saaraha cunsur-soosaaraha alfa (PDGFRA) exon 18 isbeddel (oo ay ku jiraan isbeddellada PDGFRA D842V), Iyo afar-qalliin aan qalliin ahayn ama bukaanno qaangaar ah oo GIST metastatic ah.
ORR waa sida ugu sareysa 86%, Avapritinib waxay rajo cusub u keentaa bukaanada qaba burooyinka caloosha kujira ee caloosha kujira
Bishii Nofeembar 2019, shirkii sanadlaha ahaa ee Ururka Isku-xirka Cudurka Kansarka ee Isku-xidhka (CTOS) ayaa ku dhawaaqay natiijooyinka NAVIGATOR Phase I ee tijaabada caafimaadka ee ku saabsan avapritinib ee PDGFRA exon 18 isbeddellada iyo bukaannada qaata khadka afaraad ee GIST.
1. Taariikhda cilmi baarista
Laga bilaabo Nofeembar 16, 2018, wadar ahaan 121-kii-afraad iyo wixii ka sareeya bukaanada (inta badan isbedelada KIT) iyo 43 bukaan ah GIST oo qaba PDGFRA exon 18 isbadal ayaa la qoray. Tijaabadu waxay sahmisay qiyaasta bilowga ah ee tijaabada iyada oo ah "400 mg oo afka ah hal mar maalintii", markii dambena waxay yareysey qiyaasta lagu taliyey "300 mg afka ah hal mar maalintii" sunta darteed. Bukaanku wuxuu helay Avapritinib ilaa cudurka uu ka sii socdo ama sun ah oo aan la aqbali karin.
2. Xog wax ku ool ah
Bukaannada qaba PDGFRA exon 18 mutation, waxaa jiray 3 xaaladood oo cafis dhammaystiran (OR) iyo 34 xaaladood oo cafis qayb ah (PR), iyo heerka jawaabta ujeedadu (ORR) waxay ahayd 86%. Muddada jawaabta dhexdhexaadka ah (DOR) iyo dhex-dhexaadinta badbaadada xorta ah (PFS) lama gaarin. Laga bilaabo taariikhda la jaray xogta (waqtiga daba-galka dhexe wuxuu ahaa 10.9 bilood), 78% bukaannada ayaa wali ka jawaabay.
111 GIST bukaanada leh khadka afaraad ama wixii ka sareeya, 1 wuxuu lahaa cafis dhameystiran, 23 wuxuu lahaa cafis qeyb ahaan, ORR wuxuu ahaa 22%, celceliska jawaabta dhexdhexaadka wuxuu ahaa 10.2 bilood, dhexdhexaadka PFS wuxuu ahaa 3.7 bilood, waqtiga la socoshada dhexdhexaadka wuxuu ahaa 10.8. bil.
Xagga nabadgelyada, dhacdooyinka ugu xun (AEs) badankood waa fasalka 1, 2 kuwa ugu badanna waa lallabbo, daal, dhiig-yaraan, shuban, matag, iwm; darajada 3-4 ee la xiriirta AE ≥ 2%, dhiig yari, daal, Phosphaemia oo hooseysa, hyperbilirubinemia, neutropenia iyo shuban. 10% bukaannada ayaa joojiyay daaweynta sababo la xiriira AE-yada daaweynta la xiriira.
3. Qiimaha caafimaad
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 burooyinka stromal caloosha iyo mindhicirka (GIST) with KIT and PDGFRα mutations, including the D842V mutation of the PDGFRα gene and other primary or secondary resistance mutations.
Keyless quful-PDGFRA exon 18 mutant GIST
Gastrointestinal stromal buro (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 burooyinka stromal caloosha iyo mindhicirka, 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.
Xilligan, illaa 85% burooyinka GIST waxay leeyihiin mid ka mid ah labada isbadal ee hiddo-wadaha PDGFRA iyo KIT. Isbeddelladani waxay horseedayaan soo saarista KIT aan caadi ahayn iyo borotiinnada PDGFRA, ee wada kansarka. Labadan borotiin badanaa waxaa damin kara imatinib iyo daawooyin la mid ah oo xannibaya waxqabadka borotiinka. Laakiin isbeddelka PDGFRA exon 18 waa mid aad u qaas ah, wuxuu beddelaa qaabka borotiinka PDGFRA, sidaas darteedna looga hortago daroogada inay ku xirnaato. Isbeddellada PDGFR [exon 18], "furaha" hore kuma haboona "qufulka".
Avapritinib wuxuu si xushmad leh uxidhaa PDGFRA iyo KIT borotiinka. Daraasadaha shaybaarka, daroogadu waxay kuxiran kartaa dhammaan borotiinnada isbeddelay ee PDGFRA waxayna xakameyn karaan waxqabadkooda unugyada kansarka.
Afar daawo oo hada loo ansixiyay burooyinka caloosha iyo caloosha ku jira: Avapritinib, imatinib, sunitinib, iyo rifaginib. Avapritinib kaliya waxay kuxirantahay enzymes mutant gaar ah oo loo yaqaan kinase (wareegyada cas) unugyada, halka daawooyinka la midka ah ay kuxiran yihiin kinase badan. Sawirka: Teknolojiyada Calaamadaha Qalabka.
| Daawada la bartilmaameedsaday ee loo oggolaaday burooyinka caloosha iyo caloosha ku dhaca (GIST) | Calaamadaha kale ee kansarka | Liiska guryaha |
| Gleevec | Imatinib | Cudurka sanbabada oo aad u daran (Philadelphia chromosome positive), chronic eosinophilic leukemia, Philadelphia chromosome positive chronic myeloid leukemia, dermatofibrosarcoma protuberans, myeloproliferative tumor | Lagu taxay laguna daray caymiska caafimaadka |
| Regorafenib | Stivarga | Liver cancer, kansarka mindhicirka | Lagu taxay laguna daray caymiska caafimaadka |
| Xarago | Sunitinib | Xixianai, kansarka kalyaha | Lagu taxay laguna daray caymiska caafimaadka |
| Avapritinib (Ayvakit) | maya | Liisaska lama qorin |
Horumarka kale ee cilmi baarista ee burooyinka caloosha iyo caloosha
Ripretinib
Ripretinib waa nooca II kinase inhibitor kaas oo si weyn u joojin kara isbeddellada loop firfircoon ee KIT iyo PDGFRA. Waa kinase inhibitor ah oo leh shaqo "kontoroolka wareejin", kaas oo kicin kara wareegga firfircoonida (ama kicin kara "switch") galay qaabaynta firfircoon, iyaduna, waxay joojisaa dhammaan KIT iyo PDGFRA mutants. Waxtarka Ripretinib ee moodooyinka kansarka saxda ah iyo tijaabooyinka caafimaad ee bilowga ah ayaa sidoo kale la ansixiyay in Ripretinib uu joojin karo isbeddelka caalamiga ah ee KIT ee bukaannada qaba GIST u adkaysta daroogada.
Xogta laga helay daraasadda Wejiga III (INVICTUS) waxay muujisay in bukaanada qaata Ripretinib ay 85% ka hooseeyaan halista burooyinka horumarka ama dhimashada marka la barbardhigo placebo, oo leh dhexdhexaad dhexdhexaad ah oo ah OS OS 15.1, iyo 6.6 bilood oo ku jira kooxda loo yaqaan 'placebo group'. Late GIST Late-ka ama daaweynta kor ku xusan waxay keenaysaa faa'iidooyin labalaab ah PFS iyo OS, iyo Ripretinib waxay muujineysaa dulqaad wanaagsan.
Larotrectnib
Daawada ugu horeysa ee la bartilmaameedsaday ee aan kala sooc lahayn ilaha burooyinka ee daaweynta bilowga ah-Vitrakvi ® (larotrectinib, halkan oo loo yaqaan 'larotinib'), ayaa waxaa ogolaaday bulshada burooyinka adduunka tan iyo markii loo ansixiyay suuq geynta Nofeembar 2018 Dhakhaatiirta iyo bukaanada waxay keeneen cusub rajooyinka iyo xulashooyinka.
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 kansarka tayroodh, and can be used for both adults and children. NTRK gene fusion exists in 0.7% ~ 3.6% of digestive tract tumors.
Sidaa darteed, haddii aad sameyso baaritaanka hidde-sideyaasha, waxaad marka hore arki kartaa haddii ay jiraan wax isbeddello ah oo keeni kara mucjiso badbaado, waxaad wici kartaa waaxda caafimaadka ee Shabakadda Oncologist Global si aad u fasirto warbixinta.
Waxaan rumaysanahay in marka ay soo baxayaan dawooyin badan oo la beegsanayo, bukaanada qaba stroma caloosha iyo mindhicirka
l burooyinka waxay heli karaan doorashooyin badan oo daaweyn ah iyo faa'iidooyin badbaado oo dheer. Waxaan sidoo kale rajeynayaa in daawooyinkan lagu qori karo Shiinaha sida ugu dhakhsaha badan oo lagu daro caymiska caafimaadka faa'iidada bukaanno badan.
