Tumor stromal gastrointestinal nargétkeun ubar Avapritinib

Tumor stromal Gastrointestinal nargétkeun ubar Avapritinib (Avapriny, Ayvakit, BLU-285) disatujuan ku USFDA dina 9 Januari, 2020. Ubarna nutupan dua indikasi: pikeun pengobatan pasién sawawa kalayan reseksi anu teu tiasa dioperasikeun atanapi GIST metastatik mawa reséptor faktor pertumbuhan trombosit alpha (PDGFRA) exon 18 mutation (kalebet mutasi PDGFRA D842V), Sareng penderita sawawa non-bedah atanapi metastatik GIST opat baris. 

ORR saluhur 86%, Avapritinib mawa harepan anyar pikeun penderita tumor stromal cerna

Dina bulan Nopémber 2019, rapat taunan Connective Tissue Oncology Society (CTOS) ngumumkeun hasil uji klinis NAVIGATOR Fase I dina avapritinib dina PDGFRA exon 18 mutasi sareng pasién anu nampi Gline garis kaopat.

1. latar Panilitian

Dugi ka 16 Nopémber 2018, sajumlah 121 pasien garis kaopat sareng saluhureun (utamina KIT mutasi) sareng 43 penderita GIST kalayan mutasi PDGFRA exon 18 didaptarkeun. Sidang éta ngajajah dosis awal sidang salaku "400 mg lisan sakali unggal dinten", sareng engké ngirangan dosis anu disarankeun janten "300 mg oral sakali unggal dinten" kusabab karacunan. Pasén nampi Avapritinib dugi ka kamajuan panyakit atanapi karacunan anu henteu tiasa ditampi.

2. Data épéktasi

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.

Tina 111 pasién GIST kalayan garis kaopat atanapi langkung luhur, 1 ngagaduhan rémisi lengkep, 23 gaduh rémisi parsial, ORR 22%, durasi réspon médiam nyaéta 10.2 bulan, median PFS 3.7 bulan, sareng waktos tindak lanjut median nyaéta 10.8. sasih.

Dina hal kaamanan, kaseueuran kajadian anu ngarugikeun (AEs) kalolobaanana kelas 1, 2 sareng anu paling umum nyaéta seueul, kacapean, anémia, diare, utah, jst; grade 3-4 patali AE ≥ 2%, anémia, kacapean, low Phosphaemia, hyperbilirubinemia, neutropenia and diarrhea. 10% pasien lirénkeun perlakuan kusabab AEs anu aya hubunganana sareng pangobatan.

3. nilai klinis

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 tumor stromal gastrointestinal (GIST) with KIT and PDGFRα mutations, including the D842V mutation of the PDGFRα gene and other primary or secondary resistance mutations.

Keyless konci-PDGFRA exon 18 mutant GIST

stromal gastrointestinal tumor (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 tumor stromal gastrointestinal, 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.

Ayeuna, nepi ka 85% tumor GIST gaduh salah sahiji dua mutasi gen PDGFRA sareng KIT. Mutasi ieu nyababkeun produksi protéin KIT sareng PDGFRA abnormal, anu nyababkeun kanker. Dua protéin ieu biasana bisa dipareuman ku imatinib jeung ubar sarupa nu ngahalangan aktivitas protéin urang. Tapi mutasi PDGFRA exon 18 pisan husus, éta ngarobah bentuk protéin PDGFRA, sahingga nyegah tamba ti ngabeungkeut eta. Pikeun mutasi PDGFR [exon 18], "konci" saméméhna henteu cocog pikeun "konci" ieu.

Avapritinib selektif ngabeungkeut protéin PDGFRA sareng KIT. Dina studi laboratorium, ubar tiasa ngabeungkeut sadaya protéin PDGFRA mutant anu diuji sareng ngahambat kagiatanana dina sél kanker.

Opat ubar anu ayeuna disatujuan pikeun tumor stromal cerna: Avapritinib, imatinib, sunitinib, sareng rifaginib. Avapritinib ngan ukur ngabeungkeut énzim mutant khusus anu disebut kinase (bunderan beureum) dina sél, sedengkeun ubar anu sami ngabeungkeut langkung seueur kinase. Gambar: Téknologi Sinyal Cell.

Kamajuan panilitian sanés tina tumor stromal cerna

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.

Data tina studi Phase III (INVICTUS) nunjukkeun yén pasién anu nampi Ripretinib ngagaduhan résiko 85% langkung handap tina tumuh tumor atanapi pati dibandingkeun plasebo, kalayan OS rata-rata 15.1 bulan, sareng 6.6 bulan dina grup plasebo. Perlakuan garis kaopat GIST telat atanapi saluhureuna nyandak kauntungan ganda tina PFS sareng OS, sareng Ripretinib nunjukkeun toleransi anu langkung saé.

Larotrectnib

Obat sasaran munggaran di dunya anu henteu ngabédakeun sumber tumor pikeun pangobatan awal-Vitrakvi ® (larotrectinib, anu salajengna disebatkeun larotinib), parantos disatujuan ku komunitas tumor global saprak éta disatujuan pikeun pamasaran dina bulan Nopémber 2018 Dokter sareng pasién parantos énggal harepan sareng pilihan.

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 kanker tiroid, 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 tumor bisa meunang leuwih pilihan perlakuan jeung kauntungan survival leuwih panjang. Kuring ogé ngarepkeun yén ubar ieu tiasa didaptarkeun di Cina pas mungkin sareng kalebet dina asuransi médis pikeun kapentingan langkung seueur pasien.