2019 yilgi NCCN yillik yig'ilishining mavzusi saraton kasalligini aniq davolash uchun biomarker testlarini kengaytirish, shuningdek, kolorektal saraton (CRC) ko'rsatmalariga yangi o'zgarishlar kiritishdir. Kolorektal saratonning 5 yillik omon qolish darajasi atigi 11% ni tashkil qiladi va NCCN davolash ko'rsatmalarining yangilangan davolash rejasi omon qolishni yaxshilashi kutilmoqda.
Currently, the FDA has approved a variety of drugs to treat colorectal cancer, of which only four are related to genetic mutations, and biomarkers need to be tested. The 2019 update of NCCN treatment guidelines for kolorektal saraton adds treatment methods based on detection of biomarkers, including EGFR, MSI-H / dMMR, BRAF + MEK, and NTRK fusion targets.
Keling, muayyan muhim yangilanishlar va og'ir ma'lumotlarni ko'rib chiqaylik:
mFOLFOXIRI + EGFR
Based on the phase II phase VOLFI trial, mFOLFOXIRI (fluorouracil + leucovorin + oxaliplatin + irinotecan) plus panitumumab for the EGFR inhibitor, for patients with unresectable metastatic colorectal cancer, these The patient’s genetic test must be: KRAS / NRAS / BRAF wild type and only the left shish mavjud.
VOLFI sinovida RAS yovvoyi tipdagi metastatik kolorektal saraton kasalligiga chalingan 96 bemor tasodifiy ravishda mFOLFOXIRIga panitumumab (n = 63) yoki faqat mFOLFOXIRI (n = 33) bilan qo'shilib, 2: 1 nisbatda tayinlangan. Birlashtirilgan panitumumab guruhining samaradorligi 85.7% ni tashkil etdi, faqatgina mFOLFOXIRI 54.5% ni tashkil etdi.
MSI / MMR
Mikrosatellit beqarorligi (MSI) va nomuvofiqlikni tuzatish (MMR) odatda irsiy bo'lmasa-da, bu BRAF V1E yo'g'on ichak saratonining 600 foizida uchraydigan Linch sindromi keltirib chiqaradigan o'smalarni istisno qilmaydi. Agar sizda kuchli oila tarixi bo'lsa, siz genetik tekshiruvdan o'tishingiz kerak.
Oxirgi ko'rsatmalar Lynch sindromida mavjud bo'lgan to'rtta mutant genni aniqlash uchun immunohistokimyadan foydalanishni ko'rsatmoqda: MLH1, MSH2, MSH6 va PMS2.
NCCN ilg'or yoki metastatik kolorektal saratonni davolash bo'yicha ko'rsatmalarda birinchi qator immunoterapiya options for patients with MSI-H and dMMR are nivolumab (nivolumab, Opdivo) or pembrolizumab (pembrolizumab, Keytruda), or nivolumab and ipilimumab (Iraq Combined therapy with Pitimab, Yervoy). These recommendations are category 2B recommendations and apply to patients who are not suitable for a combination cytotoxic chemotherapy regimen. These immunotherapy drug options are also listed in the guidelines as second- and third-line treatment recommendations for dMMR / MSI-H patients.
NTRK uchun
Larotrektinib (Larotinib, Vitrakvi) endi metastatik kolorektal saraton kasalligi bo'lgan bemorlarni davolashning ikkinchi bosqichidir. Bemorning genetik tekshiruvi ijobiy NTRK genlari sintezini aniqlashi kerak. Preparatning klinik tadqiqot ma'lumotlari 2018 New England Journal of Medicine-da chop etildi.
Shuning uchun, 2018 yil noyabr oyida FDA larotinibni kattalar va pediatrik bemorlarni shishgan qattiq o'smalari bilan davolash uchun qo'llashni ma'qulladi. Bemorda NTRK geni sintezi mavjud bo'lsa va ma'lum bir erishilgan qarshilik mutatsiyasi mavjud bo'lmasa, kasallik metastazlangan va jarrohlik rezektsiya natijasida o'lim xavfi katta bo'lishi mumkin, davolashning qoniqarli alternativ rejasi mavjud emas yoki davolanishdan keyin rivojlanish kuzatilmagan.
Ushbu to'liq saraton klinik tekshiruvida metastatik kolorektal saraton kasalligiga chalingan 4 bemor ro'yxatga olindi va 1 bemor yaxshi javob berdi.
BRAF va MEK uchun
NCCN ko'rsatmalarining ushbu yangilanishida ushbu biomarker uchun ikkita ikkinchi qatorli kombinatsiyalangan davolash usullari qo'shildi:
(1) dabrafenib (dalafinib, Tafinlar; BRAF) + trametinib (trametinib, Mekinist; MEK), ketuximab yoki panitumumab (EGFR monoklonal antikor) bilan birlashtirilgan;
(2) Encorafenib (Braftovi; BRAF) plus binimetinib (Mektovi; MEK) plus cetuximab or panitumumab.
The enkorafenib / binimetinib and EGFR inhibitor treatment regimens are supported by data from the introduction of phase III BEACON trials. In 30 patients with metastatic colorectal cancer with BRAF V600E mutation, combined treatment with encorafenib / binimetinib plus cetuximab was followed up for 18.2 months, with an estimated overall survival of 15.3 months. According to local evaluation results, the combined The effective rate of treatment was 48%, and 3 patients achieved complete remission.
Kolorektal saraton uchun NCCN ko'rsatmalarining ushbu yangilanishi saratonni davolashda genetik testning muhim rolini yana bir bor tasdiqlaydi. Yana bir davolash varianti bilan ko'proq umid bor! Saraton do'stlari genetik tekshiruv holatiga shubha qilishni to'xtatishlari kerak. Yaxshi xabar shundaki, kolorektal saraton uchun juda ko'p tasdiqlangan maqsadli dorilar mavjud. Iltimos, o'z qo'lingizdagi narsani qadrlang.
