Daawaynta la beegsaday ee kansarka mindhicirka, BRAF V600E hidda-wadaha mutation-ka ee lagu bartilmaameedsaday daawaynta kansarka mindhicirka Braftovi + Erbitux ayaa ugu dambayntii gaadhay natiijooyin wanaagsan
Xaaladda daaweynta kansarka malawadka
Kansarka mindhicirka waa mid ka mid ah burooyinka halista ah ee ugu caansan habka dheefshiidka. Sanadihii u dambeeyay, xanuunkeeda ayaa kaalinta saddexaad kaga jira adduunka marka loo eego burooyinka halista ah, heerka dhimashaduna waxa uu galay kaalinta labaad, taas oo khatar weyn ku ah nolosha iyo caafimaadka dadka. Iyada oo isbeddellada hab-nololeedka iyo qaab-dhismeedka cuntada ee muwaadiniinteena, dhacdooyinka kansarka mindhicirka ayaa guud ahaan muujisay kor u kac, waxayna noqotay dhacdooyinka labaad ee ugu sarreeya ee habka dheef-shiidka, iyo dhacdooyinka ugu sarreeya ee burooyinka khatarta ah. Marka loo eego tirakoobyada cilmi-baarista ee khuseeya, tirada kiisaska cusub ee mindhicirka kansarka ku dhaca Shiinaha ayaa la filayaa in ay dhaafto 521,000 sanadka 2018, tirada dhimashaduna waxa ay gaaraysaa 248,000.
Daraasaduhu waxay muujiyeen in qiyaastii 15% bukaanada qaba kansarka mindhicirka weyn ay yeelan doonaan isbeddelada hiddo-wadaha BRAF iyo saadaal xumo. Isbeddelka V600E waa isbeddelka hiddo-wadaha BRAF. Khatarta dhimashada bukaanada qaba BRAF V600E mutation waa inay siddo nooca duurjoogta ah ee BRAF Bukaanka laba jeer.
Isagoo wajahaya sida khatarta ah ee BRAF V600E mutation metastatic kansarka mindhicirka, tifaftiruhu wuxuu wadaagayaa qayb war wanaagsan oo xiiso leh oo dhawaan la bartay! Abriil 8, 2020, Pfizer waxay ku dhawaaqday in US FDA ay ogolaatay Braftovi® (encorafenib, connefenib) iyo Erbitux® (cetuximab, cetuximab) daawaynta isku dhafka ah (Braftovi borotokoolka laba-daroogada) waxaa loo isticmaalaa in lagu daweeyo bukaanada qaba kansarka mindhicirka ee metastatic (mCRC) kuwaas oo sita isbeddelka BRAF V600E. Bukaan-socodkani waxa ay hore u heleen hal ama laba daaweyn oo hore. Oggolaanshahan ayaa sidoo kale ka dhigaya Braftova daawaynta labaad daawaynta ugu horraysa ee la beegsado ee ay ansixisay FDA ee bukaanada qaba mCRC oo sidda isbeddellada BRAF.
Daaweynta Braftovi laba-laab iyo seddex-laab waxay si weyn u dheereysaa badbaadada
Horaantii Diseembar 2019, FDA waxay aqbashay barnaamijka daroogada cusub ee dheeriga ah ee barnaamijka dawada labaad ee 'Pfizer Braftovi' waxayna siisay mudnaanta dib u eegista mudnaanta. Ansixintaan waxay ku saleysan tahay natiijooyinka tijaabada bukaan socodka ee wajiga 3aad ee BEACON CRC.
Daraasadda waxaa lagu sameeyay bukaanno qaba BRAF V600E mutant mCRC oo horay u soo maray ka dib markii ay heleen hal ama laba daaweyn. Waxtarka iyo amniga qorshaha daaweynta ritica oo ay weheliso daawo (xakameyn).
Shaxda 1: Qorshaha daawaynta ee koox kasta
| Daawada labaad | Braftovi (dhiirafenib, Connefini) |
| Daawada labaad | Erbitux (cetuximab, cetuximab) |
| Barnaamijka saddex-daawo | Braftovi (dhiirafenib, Connefini) |
| Barnaamijka saddex-daawo | Erbitux (cetuximab, cetuximab) |
| Barnaamijka saddex-daawo | Mektovi (binimetinib, bemetinib) |
| Kooxda xakamaynta | Erbitux (cetuximab, cetuximab) |
| Kooxda xakamaynta | Irinotecan ama FOLFIRI (folinic acid, fluorouracil iyo irinotecan) |
Natiijooyinka ugu muhiimsan ee cilmi baarista
1. Badbaadinta dhexdhexaadka (OS): 9.0 bilood oo ka tirsan kooxda daaweynta ee seddex-geesoodka ah
8.4 bilood oo ka tirsan kooxda daaweynta ee labada daaweyn ah
Kooxda xakamaynta waa 5.4 bilood
2. Badbaadinta horumarka-bilaashka ah: 4.3 bilood ee kooxda daaweynta seddex geesoodka ah
4.2 bilood oo loogu talagalay kooxda daaweynta laba-geesoodka ah
Kooxda xakamaynta waa 1.5 bilood
3. Heerka badbaadada 6-bilood: 71% ee kooxda daweynta seddexleyda ah
65% ee kooxda daaweynta labada daaweyn ah
Kooxda xakamaynta waa 47%
4. Heerka Ka-Dhaafka Ujeeddada (ORR): 26% oo ah koox daaweyn saddex-laab ah
20% ee kooxda daaweynta labada daaweyn ah
Kooxda xakamaynta waa 2%
Sawirka bidix wuxuu isbarbar dhigayaa saddexda daw ee dawada raftovi iyo OS ee kooxda xakamaynta, sawirka midigna wuxuu isbarbar dhigayaa labada daawo ee raftovi iyo OS ee kooxda xakamaynta
Guud ahaan, marka la barbardhigo Erbitux iyo nidaamyada daaweynta ee ay ka kooban tahay irinotecan, waxtarka labada daroogo iyo saddexda daawo ma kala duwana, waxaana jira waxyeellooyin caafimaad oo yar.
Baadhe Maamule Dr. Scott Kopetz ayaa yidhi: “Bukaan ahaan oo hore loogu daweeyey BRAF V600E mutant metastatic colorectal cancer, Braftovi + Erbitux (conefinil + cetuximab) ayaa ah daaweynta ugu horeysa ee kaliya ee lala bartilmaameedsanayo Tani waa ikhtiyaarka daaweynta cusub ee bukaanada sida xun ay ugu baahan yihiin. “
Mabaadi'da isku-darka daaweynta Braftovi iyo tilmaamaha
Walaxda firfircoon ee dawooyinka Braftovi binimetinib waa molecule yar oo afka laga qaato BRAF inhibitor, iyo Mektovi's farmaceutical walaxda encorafenib waa molecule yar oo afka laga qaato MEK inhibitor. MEK iyo BRAF waa laba kinases oo borotiin ah oo muhiim ah oo ku jira dariiqa calaamadaynta MAPK (RAS-RAF-MEK-ERK).
Daraasaduhu waxay muujiyeen in waddadani ay nidaamiso hawlo badan oo muhiim ah oo ay ku jiraan kororka unugyada, kala duwanaanta, badbaadada, iyo angiogenesis. Kansarro badan, sida melanoma, kansarka mindhicirka, iyo kansarka tayroodh, borotiinada ku jira dariiqan calaamadaynta ayaa la muujiyay inay si aan caadi ahayn u hawl-galiyeen.
Dalka Maraykanka, isku-darka Braftovi + Mektovi ayaa loo ogolaaday melanoma aan la soo saari karin ama metastatic melanoma ah oo leh BRAF V600E ama BRAF V600K mutations. Braftovi kuma habboona daawaynta duurjoogta BRAF melanoma. Yurub dhexdeeda, isku-darka waxaa loo oggolaaday dadka waaweyn ee leh melanoma aan la daweyn karin ama metastatic oo leh isbeddel BRAF V600. Japan gudaheeda, isku darka ayaa loo ansixiyay BRAF-mutated melanoma aan la daweyn karin.
| Magaca Ingiriisiga | Magaca Shiinaha | Target | saaraha | Tilmaamayaasha | Medicare |
| Trametinib (Mekinist) | Trametinib | MEK | Novartis (ka baxsan) | Isla sida kor ku xusan | maya |
| Vemurafenib (Zelboraf) | Verofinil (Verofinil, Zuobofu) | WALAAL | Roche Gold iyo Silver Tektronix (bannaanka) | Melanoma | Haa, waxaa lagu daray caymiska caafimaadka |
| Cobimetinib (Cotelic) | Cobitinib | MEK | Roche Gold iyo Silver Tektronix (bannaanka) | Isla sida kor ku xusan | maya |
| Encorafenib (Braftovi) | Connefini | WALAAL | Diyaargarowga BioPharma | Melanoma | maya |
| Binimetinib (Mektovi) | Bemetinib | MEK | Diyaargarowga BioPharma | Isla sida kor ku xusan | maya |
Tilmaamaha NCCN ee 2019 ee Kansarka Midabaynta ayaa ku daraya laba daaweyn oo cusub oo EGFR / BRAF / MEK ah oo saddex-laab ah oo isku-dhafan oo loogu talagalay bukaannada qaba cudurka horumarsan ee BRAF V600E-is-beddelka-positive, kuwaas oo kala ah:
[1] Dabrafenib + Trametinib + Cetuximab / Panitumumab (Cetuximab / Panitumumab)
[2] Encorafenib (conefinil) + Binimetinib (bimetinib) + Cetuximab / Panitumumab (cetuximab / panitumumab)
Xiaobian waxbaa la dhahaa
Xilliga daawaynta la beegsanayo, bukaan kasta oo qaba kansarka mindhicirka waa inuu ka gudbiyaa ogaanshaha MSI, falanqaynta isbeddelka ee RAS iyo BRAF, oo uu sameeyo cod-weyneysiinta HER2, NTRK iyo ogaanshaha hidda-wadaha kale intii suurtagal ah. Tijaabada hidda-socodka (NGS) ayaa lagu dari doonaa heerka weyn ee baaritaanka bilowga ah ee bukaannada intooda badan. Saaxiibada kansarka ee lagu sameeyay baaritaanka hidda-socodka waxay u diri karaan warbixinta waaxda caafimaadka si ay u tarjumaan si ay u eegaan haddii ay jirto ikhtiyaar daawaynta habboon.
Tifaftiruhu wuxuu rumaysan yahay in mustaqbalka ay jiri doonto horumar cilmi baaris oo cusub iyo daawooyinka ugu fiican ee kansarka mindhicirka. Kaliya khabiirada kansarka ee ugu sarreeya gudaha iyo dibadda ayaa leh khibrad caafimaad oo qani ah. Bukaanjiifka kansarka mindhicirka waxay codsan karaan awood iyagoo adeegsanaya la-talinta Khabiirka Shabakadda Oncologist Global, hel ogaanshaha iyo qorshaha daaweynta ugu fiican.
