Maqolani boshlashdan oldin, fanga birinchi qarash.
MSI-H, MSS, MSI-L haqida tushuncha
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MSS (MicroSatellite barqarorligi), mikrosatellit barqarorligi, MSI bilan solishtirganda, aniq MSI yo'q.
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MSI-H (MicroSatellite Instability-Yuqori, yuqori chastotali mikrosatellit beqarorligi), ya'ni mikrosatellitning beqarorligi chastotasi yuqori, odatda 30% dan yuqori;
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MSI-L (MicroSatellite Instability-Past, past chastotali mikrosatellit beqarorligi), ya'ni mikrosatellitning beqarorligi chastotasi past, odatda 30% dan kam.
Friends who are concerned about the latest progress in cancer treatment know that the broad-spectrum anticancer drugs pembrolizumab and nivolumab have been approved for the treatment of all solid tumor patients with MSI-H (high microsatellite instability). Especially for colorectal patients, the detection rate of MSI-H is relatively high, so some cancer patients benefit from this type of treatment to prolong survival.
In the NCCN advanced or metastatic colorectal cancer treatment guidelines, the first-line immunotherapy 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.
Rezektsiya qilib bo'lmaydigan mahalliy rivojlangan yoki metastatik yo'g'on ichak saratoni bilan kasallangan yoki kamida ikkita oldingi tizimli kimyoterapiya rejimiga chidamli bo'lgan bemorlar uchun ularning 95% MSI-H o'rniga MSSni aniqlay oladi. Xo'sh, MSS kolorektal saraton bemorlarini qanday tanlash mumkin?
Recently, the IMblaze370 trial was published as a phase III open-label trial, and 363 patients with metastatic colorectal cancer whose genetic test results were MSS were randomly assigned to atezolizumab (atezolizumab) in combination with cobimetinib (cobititib) at 2: 1: 1 Ni, MEK targeted drug) group, attuzumab monotherapy group, regorafenib (regorafenib, multi-target kinase inhibitor) group. Patients with MSS colorectal cancer have historically not responded to immunotherapy.
Ushbu tadqiqot natijalari yana bir bor tasdiqlaydi: MSS yo'g'on ichak saratoni bilan kasallangan bemorlar immunoterapiya (PD-L1) atuzumab preparatiga yaxshi javob bermaydi. Atezumabning kobtinib guruhi bilan birgalikda o‘rtacha umumiy umr ko‘rish davomiyligi 8.87 oyni tashkil etdi, yakka immunoterapiya yoki kombinatsiyalanganidan qat’i nazar, atezumab guruhidagi 7.10 oy va regofenib guruhida 8.51 oy omon qolishning sezilarli foydasi yo‘q.
O'rtacha rivojlanishsiz omon qolish uchun uchta davolash guruhi 1.91 oy, 1.94 oy va 2.00 oyni tashkil etdi, hech qanday farq yo'q. 3/4 darajali nojo'ya ta'sirlar darajasi kombinatsiyalangan terapiya guruhida 61%, atuzumab monoterapiya guruhida 31% va regofenib guruhida 58% ni tashkil etdi.
"Ushbu natijalar MSS va MSI-H o'rtasidagi kuchli biologik farqlarni ta'kidlaydi va bu ikki kasallik turi o'rtasidagi turli xil davolash ehtiyojlarini ta'kidlaydi", dedi Texas universiteti Anderson saraton markazi tadqiqotchisi doktor Keti Eng.
That is to say, the colorectal cancer patients whose MSS is found by genetic testing do not recommend the choice of immunotherapy, and use other methods instead. At present, the targets and targeted drugs that can be achieved by patients with colorectal cancer are:
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VEGF: Bevacizumab, Apsip
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VEGFR: ramucirumab, rigofinib, frukintinib
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EGFR: cetuximab, panitumumab
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PD-1 / PDL-1: pembrolizumab, nivolumab
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CTLA-4: Ipilimumab
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BRAF: Velofini
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NTRK: Larotinib
Agar boshqa mos keladigan maqsadli mutatsiyalar aniqlansa, tegishli maqsadli dori terapiyasini tanlash mumkin.
Kolorektal saraton bilan og'rigan bemorlar uchun siz barcha odamlar uchun mos bo'lgan sitotoksik kimyoterapevtik vositalar guruhining kombinatsiyasi bo'lgan FOLFOXIRI (fluorourasil + leykovorin + oksaliplatin + irinotekan) standart kimyoviy terapiya to'plamini tanlashingiz mumkin.
After drug resistance, the genetic test result is not MSI-H. You can also choose multi-target kinase inhibitors regorafenib (regorafenib, Stivarga) and TAS-102 (trifluridine / tipiracil; Lonsurf).
Cetuximab is also a star drug often selected by colorectal patients, which is a drug that often appears in individualized treatment plans. Evaluation methods include: Is the tumor on the left or right? Does it contain KRAS / NRAS mutations? Before selecting cetuximab or panitumumab, the RAS gene mutation must be considered.
