Kolorektal saraton uchun mo'ljallangan terapiya

Kolorektal saratonga qaratilgan dorilar nima?

17 years ago, the number of drugs available for advanced colorectal cancer was very limited. There were only a few chemotherapeutic drugs and almost no targeted drugs. Once diagnosed, the survival period is only between half a year and one year. But now, cancer treatment is entering the era of precision treatment, and more and more targeted and immune drugs are on the market.

In the 2017 version of the colorectal cancer treatment guidelines, the recommendations for genetic testing only involve KRAS, NRAS, dMMR, and MSI-H. In the latest treatment guidelines for 2019, new targets such as BRAF, HER2, NTRK are newly included Point, through genetic testing, to understand more molecular information about colorectal cancer, can help us find more medication options. The average patient survival rate is more than 3 years, which is a huge improvement brought by precision medicine.

Kolorektal saraton kasalligida qaysi genlarni tekshirish kerak?

Tashxis qo'yilgandan so'ng, shifokorlar kasallikning kichik guruhini aniqlash uchun metastatik kolorektal saraton (mCRC) bilan kasallangan har bir bemorni iloji boricha erta sinab ko'rishlari kerak, chunki bu ma'lumotlar davolash prognozini taxmin qilishi mumkin, masalan, anti-EGFR terapiyasini taklif qiladigan HER2 amplifikatsiyasi. Quyidagi genlar sinovdan o'tkazilishi kerak!

MSI, BRAF, KRAS, NRAS, RAS, HER2, NTRK.

Hozirgi vaqtda davolash uchun mo'ljallangan maqsadli dorilar va maqsadli dorilar

VEGF: bevacizumab, qabul qilish

VEGFR: Ramulizumab, Regigofinil, Fruquintinib

EGFR: Cetuximab, Panitumumab

PD-1 / PDL-1: Pamumab, Navumab

CTLA-4: Ipilizumab

BRAF: Vimofenib

NTRK: Larotinib

List of colorectal cancer targeting and immunotherapy drugs that have been approved so far at home and abroad:

Bevacizumab uchun ko'rsatmalar: metastatik kolorektal saraton va rivojlangan, metastatik yoki takroriy kichik hujayrali bo'lmagan o'pka saratoni.

Trastuzumab uchun ko'rsatmalar: HER2-positive metastatic breast cancer, HER2-positive early breast cancer, and HER2-positive metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma.

Pertuzumabning ko'rsatmalari: This product is suitable for combination with trastuzumab and chemotherapy as an adjuvant treatment for patients with HER2-positive early breast cancer with a high risk of recurrence.

Nivolumabning ko'rsatmalari: negative epidermal growth factor receptor (EGFR) gene mutation and anaplastic lymphoma kinase (ALK) negative, disease progression or intolerable locally advanced or metastatic disease after previous platinum-containing chemotherapy Adult patients with non-small cell lung cancer (NSCLC).

Regorafenib ko'rsatmalari: previously treated metastatic colorectal cancer patients. Durvalumab, Tremelimumab, Ipilimumab, lapatinib are not yet available in China.

Kolorektal maqsadli terapiya (2019 yil yangilanishi)

1. Kras-salbiy kolorektal saratonni davolash

KRAS yo'g'on ichak saratoni kimyoterapiya bilan birgalikda maqsadli kimyoterapiya uchun standart birinchi darajali davolash usuli hisoblanadi. Xo'sh, qanday kimyoterapiya tanlanadi?

Maqsadli dori-darmonlarni tanlashda uzoqroq operatsion tizimga ega bo'lgan kimyoviy terapiya rejimini tanlash tavsiya etiladi, ya'ni ketuximab FOLFOX uchun, bevacizumab esa FOLFIRI uchun ko'proq mos keladi. Qaysi rejani tanlash o'ziga xos klinik tahlilga bog'liq:

Agar davolanishga umid bo'lsa, ketuximab kimyoviy terapiya bilan birgalikda odatda afzalroq bo'ladi, chunki ketuximabning so'nggi ob'ektiv samaradorligi bevacizumabdan yuqori;

Davolab bo'lmaydigan kasallikka chalingan bemorlar uchun bevatsizumab kimyoterapiya bilan birgalikda birinchi qatorda, so'ngra ketuximab yoki panitumumab ishlatilishi mumkin.

2. Kras-musbat kolorektal saraton kasalligini davolash

Yo'g'on ichakning metastatik saratoniga chalingan bemorlar RAS mutatsion holatini, shu jumladan KRAS va NRASni tekshirishlari kerak va hech bo'lmaganda KRAS exon 2 holati aniq bo'lishi kerak.

Iloji bo'lsa, KRAS Exon 2 va NRAS mutatsion holatidan tashqari boshqa ekzonlar holati aniqlanishi kerak.

Bevacizumab combined with two-drug chemotherapy can bring PFS (median progression-free survival) and OS (overall survival) benefits to patients with KRAS mutations.

RAS mutatsiyasiga ega bemorlar uchun ketuximabdan foydalanish umumiy samaradorlikka salbiy ta'sir ko'rsatishi mumkin. KRAS yoki NRAS mutatsiyasiga ega bemorlar ketuximab yoki panitumumab dan foydalanmasliklari kerak.

3. BRAF mutant kolorektal saraton kasalligini davolash

Yo'g'on ichak saratoni bilan kasallangan bemorlarning 7-10% BRAF V600E mutatsiyasiga ega. BRAF V600E mutatsiyasi BRAF faollashtirilgan mutatsiyadir va BRAF mutatsiyalarining eng yuqori ulushiga ega. Noyob klinik xususiyatlarga ega: asosan o'ng gemikolonda paydo bo'ladi; dMMR nisbati yuqori, 20% ga etadi; BRAF V600E mutatsiyasi yomon prognozga ega; atipik metastatik naqshlar;

Tadqiqotlar shuni ko'rsatdiki, FOLFOXIRI + bevacizumab BRAF mutatsiyasiga ega bemorlar uchun eng yaxshi davo bo'lishi mumkin. 2019 V2 NCCN yo'riqnomasida BRAF V600E metastatik kolorektal saraton kasalligini davolashning ikkinchi bosqichli usullari tavsiya etiladi: verofinib + irinotekan + ketuximab / panitumumab Dabarafenib + trametinib + cetuximab / panit MAb

Encorafenib + Binimetinib + Cetux / Pan

4. HER2 kuchaytirish

HER2 amplification or overexpression is found in 2% to 6% of patients with advanced or metastatic colorectal cancer. Pertuzumab and trastuzumab bind to different HER2 domains to produce synergistic inhibitory effects on tumor cells. MyPathway is the first clinical study to investigate the efficacy of Pertuzumab + Trastuzumab in patients with HER2 expansion metastatic colorectal cancer (regardless of KRAS mutation status). This study shows that HER2 dual-targeted therapy, Pertuzumab + Trastuzumab, is well tolerated or could be used as a treatment option for patients with HER2 expansion metastatic colorectal cancer. Early genetic testing to identify HER2 mutations and consider early use of HER2 targeted therapy may benefit patients.

5. NTRK termoyadroviy kolorektal saraton kasalligini davolash

NTRK sintezi yo'g'on ichak saratoni bilan kasallangan bemorlarning taxminan 1-5 foizida uchraydi va NGS testini o'tkazish tavsiya etiladi. Lorarektinib qattiq o'smalari bo'lgan bemorlarda NTRKni qayta tashkil etish uchun tasdiqlangan, ORR darajasi 62% va ulardan 3 tasi CRC bilan. Larotinib va ​​emtricinib kabi TRK inhibitörlerinin paydo bo'lishi NTRK gen termoyadroviy CRC uchun yangi terapevtik g'oyalarni beradi.

Metastatik kolorektal saraton kasalligiga chalingan 75 yoshli ayol juda baxtli:

Birlamchi yo'g'on ichak shishi.

Peritoneal saraton.

Jigar metastazlari.

1600 mg / m 2 emtricinib haftasiga bir marta ketma-ket 4 kun davomida (ya'ni 4 kun / 3 kun dam olish) va har 3 kunda ketma-ket 28 hafta davomida og'iz orqali yuboriladi. Ortda
sakkiz haftalik davolanishda jarohatlar sezilarli darajada kamaydi.

Yakunlovchi tushuntirishlar

Maqsadli terapiya davriga kirib, kolorektal saraton kasalligiga chalingan har bir bemor MSI tekshiruvidan, RAS va BRAF mutatsion tahlillaridan o'tishi va imkon qadar HER2 amplifikatsiyasini o'tkazishi, NTRK kabi genlarni aniqlash va genetik tekshiruv (NGS) kiritilishi kerak. katta bemorlarning ko'pchiligi uchun dastlabki tekshiruv mezonlari.

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