Gastrointestinal stromal tumor yakanangana nemishonga Avapritinib (Avapriny, Ayvakit, BLU-285) inogamuchirwa neUSFDA musi wa9 Ndira, 2020. Mushonga uyu unovhara zviratidzo zviviri: zvekurapa kwevakuru varwere vane isingagone resection kana metastatic GIST inotakura platelet-yakatorwa kukura chinhu chinogamuchira alpha (PDGFRA) exon 18 mutation (kusanganisira PDGFRA D842V mutation), Uye ina-mitsara isiri-yekuvhiya kana metastatic GIST vakuru varwere.
ORR yakakwira kunge 86%, Avapritinib inounza tariro nyowani kuvarwere vane dumbu remudumbu stromal tumors.
MunaNovember 2019, musangano wepagore weConnective Tissue Oncology Society (CTOS) yakazivisa mhedzisiro ye NAVIGATOR Phase I kiriniki kutongwa pane avapritinib mu PDGFRA exon 18 mutations uye varwere vanowana mutsara wechina GIST.
1. Kutsvaga mamiriro
Kubva munaNovember 16, 2018, yakazara ye121 yechina-mutsara uye pamusoro pevarwere (kunyanya KIT mutations) uye 43 GIST varwere vane PDGFRA exon 18 shanduko vakanyoreswa. Muedzo wakaongorora muyero wekutanga wekuyedza se "400 mg yemuromo kamwe pazuva", uye yakazodzora dhosi inokurudzirwa ku "300 mg yemuromo kamwe pazuva" nekuda kwehuturu. Murwere akagamuchira Avapritinib kudzamara hosha ichiwedzera kana huturu husingagamuchiriki.
2. Efficacy data
For patients with PDGFRA exon 18 mutation, there were 3 cases of complete remission (OR) and 34 cases of partial remission (PR), and the objective response rate (ORR) was 86%. The median duration of response (DOR) and median progression-free survival (PFS) were not reached. As of the data cut-off date (median follow-up time was 10.9 months), 78% of patients still responded.
Pakati pe111 varwere veGIST vane mutsara wechina kana pamusoro, 1 yaive nekuregererwa kwakazara, 23 yaive neregererwo pashoma, ORR yaive 22%, nguva yepakati yekupindurwa yaive 10.2 mwedzi, median PFS yaive 3.7 mwedzi, uye median yekutevera-nguva yaive 10.8. mwedzi.
Panyaya yekuchengetedzeka, zviitiko zvakashata zvakanyanya (AEs) zvinonyanya kuve giredhi 1, 2 uye zvakajairika ndezvekushushikana, kuneta, kupererwa neropa, manyoka, kurutsa, nezvimwe. giredhi 3-4 rakabatana AE ≥ 2%, kupererwa neropa, kuneta, yakaderera Phosphaemia, hyperbilirubinemia, neutropenia uye manyoka. 10% yevarwere vakarega kurapwa nekuda kwehutano hwakanangana neAEs.
3. Kukosha kwekiriniki
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 gastrointestinal stromal tumors (GIST) with KIT and PDGFRα mutations, including the D842V mutation of the PDGFRα gene and other primary or secondary resistance mutations.
Kiyi isina kukiya-PDGFRA exon 18 mutant GIST
Gastrointestinal stromal tumarara (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 gastrointestinal stromal tumors, 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.
Parizvino, anosvika makumi masere neshanu muzana emamota eGIST ane imwe yeaya maviri gene mutations PDGFRA neKIT. Idzi shanduko dzinotungamira mukugadzirwa kwemapuroteni eKIT nePDGFRA, ayo anotyaira cancer. Mapuroteni maviri aya anogona kazhinji kudzimwa neimatinib nemimwe mishonga yakafanana inovhara kuita kweprotein. Asi shanduko yePDGFRA exon 85 yakakosha zvikuru, inoshandura chimiro cheprotein yePDGFRA, nokudaro ichidzivirira mushonga kubva pakusunga kwairi. Kune PDGFR [exon 18] mutation, "kiyi" yapfuura haina kukodzera "kukiya" iyi.
Avapritinib inosarudza inosunga PDGFRA uye KIT mapuroteni. Muzvidzidzo zvevarabhoritari, mushonga unogona kusunga kune ese akaedzwa mutant PDGFRA mapuroteni uye kutadzisa zvavanoita mumasero ekenza.
Mishonga mina parizvino inogamuchirwa kumatumbu emimba: Avapritinib, imatinib, sunitinib, uye rifaginib. Avapritinib inosunga chete kune mamwe enzyme akachinjika anonzi kinases (madenderedzwa matsvuku) mumasero, nepo mishonga yakafanana ichisunga kune mamwe ma kinases. Mufananidzo: Cell Signaling Technology.
| Chinangwa chemishonga chinotenderwa gastrointestinal stromal tumor (GIST) | Zvimwe zvinoratidza gomarara | Zvemumba zvinyorwa |
| Gleevec | Imatinib | Acute lymphocytic leukemia (Philadelphia chromosome positive), chronic eosinophilic leukemia, Philadelphia chromosome positive chronic myeloid leukemia, dermatofibrosarcoma protuberans, myeloproliferative tumor | Yakanyorwa uye yakaiswa muinishuwarenzi yekurapa |
| Regorafenib | Stivarga | Liver cancer, kenza yakajeka | Yakanyorwa uye yakaiswa muinishuwarenzi yekurapa |
| Sutent | Suntinib | Xixianai, kenza yeitsvo | Yakanyorwa uye yakaiswa muinishuwarenzi yekurapa |
| Avapritinib (Ayvakit) | kwete | Asina kunyorwa |
Kumwe kutsvagurudza kufambira mberi kwematumbo emimba stromal tumors
Ripretinib
Ripretinib is a type II kinase inhibitor that can widely inhibit the activation loop mutations in KIT and PDGFRA. It is a kinase inhibitor with a “switch control” function, which can activate the activation loop (or activate the “switch”) into The active conformation, in turn, inhibits all tested KIT and PDGFRA mutants. Ripretinib’s effectiveness in preclinical cancer models and initial clinical trials also validated that Ripretinib can inhibit the universal KIT mutation in patients with drug-resistant GIST.
Dhata kubva kuChikamu III kudzidza (INVICTUS) yakaratidza kuti varwere vanogashira Ripretinib vaive ne 85% panjodzi yakaderera yekukura kwechirwere kana kufa zvichienzaniswa ne placebo, ine median OS yemwedzi 15.1, uye mwedzi 6.6 muboka re placebo. Kwapera nguva GIST yechina-mutsara kana pamusoro pekurapwa kunounza mabhenefiti maviri ePFS uye OS, uye Ripretinib inoratidza zviri nani shiviriro.
Larotrectnib
Mushonga wepasirose wekutanga wakanangana nemushonga usingasiyanise mabviro emota ekurapa kwekutanga-Vitrakvi ® (larotrectinib, ichatumidzwa kunzi larotinib), yakagamuchirwa nenharaunda yepasirese yemota kubvira payakabvumidzwa kushambadzira munaNovember 2018 Vanachiremba nevarwere vaunza zvitsva tariro uye sarudzo.
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 chirwere chetachiona, and can be used for both adults and children. NTRK gene fusion exists in 0.7% ~ 3.6% of digestive tract tumors.
Therefore, if you do a genetic test, you can first see if there are any mutations that may bring a miracle of survival, you can call the medical department of the Global Oncologist Network to interpret the report.
I believe that with the advent of more and more targeted drugs, patients with gastrointestinal stroma
l mamota anogona kuwana mamwe maitiro ekurapa uye mabhenefiti ekurarama kwenguva refu. Ndinovimba zvakare kuti mishonga iyi inogona kunyorwa muChina nekukurumidza sezvinobvira uye kuiswa muinishuwarenzi yekurapa kuitira kubatsira varwere vakawanda.
