Yo'g'on ichak saratonini maqsadli davolash, BRAF V600E gen mutatsion yo'g'on ichak saratonini maqsadli davolash Braftovi + Erbitux nihoyat ijobiy natijalarga erishdi.
Kolorektal saraton kasalligini davolash holati
Colorectal cancer is one of the most common malignant tumors in the digestive system. In recent years, its morbidity ranks third in the world in terms of malignant tumors, and its mortality rate ranks second, which seriously threatens people’s lives and health. With the changes in the living habits and dietary structure of our nationals, the incidence of kolorektal saraton has generally shown an upward trend, and has become the second highest incidence of digestive system, and the highest incidence of malignant tumors. According to relevant research statistics, the number of new cases of colorectal cancer in China is expected to exceed 521,000 in 2018, and the number of deaths is as high as 248,000.
Tadqiqotlar shuni ko'rsatdiki, metastatik kolorektal saraton kasalligiga chalingan bemorlarning taxminan 15% BRAF gen mutatsiyasiga va yomon prognozga ega bo'ladi. V600E mutatsiyasi eng keng tarqalgan BRAF gen mutatsiyasidir. BRAF V600E mutatsiyasiga chalingan bemorlarning o'lim xavfi yovvoyi turdagi BRAF geni Bemorlarni ikki marta olib yurishdan iborat.
Faced with such a dangerous BRAF V600E mutation metastatic colorectal cancer, the editor shares a piece of exciting good news learned recently! On April 8, 2020, Pfizer announced that the US FDA has approved Braftovi® (encorafenib, connefenib) and Erbitux® (cetuximab, cetuximab) combination therapy (Braftovi two-drug protocol) is used to treat patients with metastatic colorectal cancer (mCRC) who carry the BRAF V600E mutation. These patients have already received one or two pre-treatments. This approval also makes the Braftovi ikkinchi dori rejimi FDA tomonidan BRAF mutatsiyalari bo'lgan mCRC bo'lgan bemorlar uchun tasdiqlangan birinchi maqsadli terapiya.
Braftovi ikki va uch martalik davolash hayotni sezilarli darajada uzaytiradi
2019 yil dekabr oyidayoq FDA Pfizer Braftovi Ikkinchi Dori Dasturining qo'shimcha dori-darmonga oid yangi arizasini qabul qildi va ko'rib chiqishning ustuvor malakasini berdi. Ushbu tasdiqlash BEACON CRC Phase 3 klinik sinovlari natijalariga asoslangan.
Tadqiqot ilgari bir yoki ikkita terapiya o'tkazilgandan so'ng rivojlangan BRAF V600E mutant mCRC bilan kasallangan bemorlarda o'tkazildi. Ritikaning davolash rejasining samaradorligi va xavfsizligi dorilar bilan birgalikda (nazorat).
1-jadval: Har bir guruhning dori-darmonlar rejasi
| Ikkinchi tibbiyot | Braftovi (enkorafenib, Konnefini) |
| Ikkinchi tibbiyot | Erbitux (setuksimab, setuksimab) |
| Uchta dori dasturi | Braftovi (enkorafenib, Konnefini) |
| Uchta dori dasturi | Erbitux (setuksimab, setuksimab) |
| Uchta dori dasturi | Mektovi (binimetinib, bemetinib) |
| Nazorat guruhi | Erbitux (setuksimab, setuksimab) |
| Nazorat guruhi | Irinotekan yoki FOLFIRI (folin kislotasi, ftorurasil va irinotekan) |
Asosiy tadqiqot natijalari
1. Median omon qolish (OS): uch marta terapiya guruhida 9.0 oy
Dual terapiya guruhida 8.4 oy
Nazorat guruhi - 5.4 oy
2. Progressiyasiz omon qolish: uch marta terapiya guruhida 4.3 oy
Ikki tomonlama terapiya guruhi uchun 4.2 oy
Nazorat guruhi - 1.5 oy
3. 6 oylik hayot darajasi: uch marta terapiya guruhida 71%
Ikki tomonlama terapiya guruhida 65%
Nazorat guruhi 47%
4. Ob'ektiv remissiya darajasi (ORR): uch marta terapiya guruhida 26%
Ikki tomonlama terapiya guruhida 20%
Nazorat guruhi 2%
Chapdagi rasmda raftovining uch dori rejimi nazorat guruhining OS bilan, o'ngdagi rasmda esa raftovining ikki dori rejimi nazorat guruhining OS bilan taqqoslangan.
Umuman olganda, Erbitux va irinotekanni o'z ichiga olgan davolash sxemalari bilan taqqoslaganda, ikkita dori-darmonli rejim va uchta dori-darmonli rejim samaradorligi unchalik farq qilmaydi va klinik yon ta'siri kam.
Asosiy tergovchi doktor Skott Kopets shunday dedi: "Oldindan davolangan BRAF V600E mutant metastatik kolorektal saraton kasalligiga chalingan bemor sifatida Braftovi + Erbitux (konefinil + tsetuximab) bu birinchi va yagona maqsadli terapiya. Bu bunday bemorlarga juda zarur bo'lgan yangi davolash usuli. "
Braftovi kombinatsiyalangan davolash tamoyillari va ko'rsatmalari
Braftovi’s active pharmaceutical ingredient binimetinib is an oral small molecule BRAF inhibitor, and Mektovi’s active pharmaceutical ingredient encorafenib is an oral small molecule MEK inhibitor. MEK and BRAF are two key protein kinases in the MAPK signaling pathway (RAS-RAF-MEK-ERK).
Studies have shown that this pathway regulates many key cell activities including cell proliferation, differentiation, survival, and angiogenesis. In many cancers, such as melanoma, colorectal cancer, and thyroid cancer, proteins in this signaling pathway have been shown to be abnormally activated.
Qo'shma Shtatlarda Braftovi + Mektovi kombinatsiyasi BRAF V600E yoki BRAF V600K mutatsiyalari bilan rezektsiya qilinmaydigan yoki metastatik melanoma uchun tasdiqlangan. Braftovi yovvoyi turdagi BRAF melanomasini davolash uchun mos emas. Evropada kombinatsiya BRAF V600 mutatsiyasiga ega bo'lmagan yoki metastatik melanomasi bo'lgan kattalar uchun tasdiqlangan. Yaponiyada kombinatsiya BRAF-mutatsiyaga uchragan rezektsiyasiz melanoma uchun tasdiqlangan.
| Inglizcha ism | Xitoycha ism | maqsad | ishlab chiqaruvchi | Ko'rsatkichlar | Medicare |
| Trametinib (mekinist) | Trametinib | MEK | Novartis (tashqarida) | Yuqoridagi kabi | Yo'q |
| Vemurafenib (Zelboraf) | Verofinil (Verofinil, Zuobofu) | AKA | Roche Gold va Silver Tektronix (tashqarida) | Melanoma | Ha, tibbiy sug'urtaga kiritilgan |
| Kobimetinib (kotellik) | Kobitinib | MEK | Roche Gold va Silver Tektronix (tashqarida) | Yuqoridagi kabi | Yo'q |
| Enkorafenib (Braftovi) | Konnefini | AKA | Array BioFharma | Melanoma | Yo'q |
| Binimetinib (Mektovi) | Bemetinib | MEK | Array BioFharma | Yuqoridagi kabi | Yo'q |
2019-yilgi NCCN yoʻriqnomasi yoʻgʻon ichak saratoni boʻyicha yoʻriqnomasi rivojlangan BRAF V600E mutatsion musbat ilgʻor kasalligi boʻlgan bemorlar uchun ikkita yangi EGFR/BRAF/MEK uch ingibitorining kombinatsiyalangan terapiyasini qoʻshadi, xususan:
[1] Dabrafenib + Trametinib + Cetuximab / Panitumumab (Cetuximab / Panitumumab)
[2] Enkorafenib (konefinil) + Binimetinib (bimetinib) + Cetuximab / Panitumumab (cetuximab / panitumumab)
Xiaobianning aytadigan gaplari bor
Maqsadli terapiya davrida yo'g'on ichak saratoni bilan og'rigan har bir bemor MSI aniqlash, RAS va BRAF mutatsion tahlilidan o'tishi va iloji boricha HER2 kuchaytirilishi, NTRK va boshqa genlarni aniqlashni amalga oshirishi kerak. Genetik test (NGS) bemorlarning ko'pchiligi uchun dastlabki tekshiruv standartiga kiritiladi. Genetik tekshiruvdan o'tgan saraton kasalligiga chalingan do'stlar tegishli davolash varianti bor-yo'qligini bilish uchun talqin qilish uchun hisobotni tibbiy bo'limga yuborishlari mumkin.
Tahririyatning fikricha, kelajakda ko'proq so'nggi tadqiqotlar va yo'g'on ichak saratoni uchun eng yaxshi dorilar bo'ladi. Faqatgina uyda va xorijda saraton bo'yicha eng yaxshi mutaxassislar boy klinik tajribaga ega. Kolorektal saraton bilan og'rigan bemorlar Global Onkolog tarmog'i ekspert maslahati orqali vakolatga murojaat qilishlari, eng yaxshi tashxis va davolash rejasini olishlari mumkin.
