Ukwelashwa okuhlosiwe komdlavuza we-colorectal, i-BRAF V600E gene mutation ehlosiwe yokwelapha umdlavuza we-colorectal i-Braftovi + Erbitux ekugcineni izuze imiphumela emihle.
Isimo sokwelashwa komdlavuza we-colorectal
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 umdlavuza colorectal 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.
Ucwaningo luye lwabonisa ukuthi cishe u-15% weziguli ezinomdlavuza we-metastatic colorectal uzoba nokuguqulwa kofuzo lwe-BRAF kanye nokubikezela okubi. Ukuguqulwa kwe-V600E ukuguqulwa kofuzo okuvame kakhulu kwe-BRAF. Ingozi yokufa kweziguli ezinokuguqulwa kwe-BRAF V600E ukuthwala uhlobo lwasendle lwe-BRAF gene Iziguli kabili.
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 UBraftovi uhlobo lwesibili lwemithi yokwelapha ehlosiwe yokuqala egunyazwe i-FDA ezigulini ezine-mCRC ephethe izinguquko ze-BRAF.
Ukwelashwa kwe-Braftovi okuphindwe kabili nokukathathu kukhulisa kakhulu ukusinda
Ekuqaleni kukaZibandlela wezi-2019, i-FDA yamukela isicelo sesidakamizwa esisha sePfizer Braftovi Second Drug Programme futhi yanikeza ukufaneleka kokubuyekezwa okubalulekile. Lokhu kugunyazwa kusekelwe emiphumeleni yokuhlolwa komtholampilo kwe-BEACON CRC Isigaba 3 somtholampilo.
Ucwaningo lwenziwa ezigulini ezine-BRAF V600E eguquguqukayo ethuthukisiwe mCRC eyayithuthuke ngaphambilini ngemva kokuthola ukwelashwa okukodwa noma okubili. Ukusebenza nokuphepha kohlelo lokwelashwa kwe-ritica kuhlanganiswe nemithi (control).
Ithebula 1: Uhlelo lwemithi yeqembu ngalinye
| Umuthi wesibili | I-Braftovi (encorafenib, Connefini) |
| Umuthi wesibili | I-Erbitux (cetuximab, cetuximab) |
| Uhlelo lwezidakamizwa ezintathu | I-Braftovi (encorafenib, Connefini) |
| Uhlelo lwezidakamizwa ezintathu | I-Erbitux (cetuximab, cetuximab) |
| Uhlelo lwezidakamizwa ezintathu | I-Mektovi (i-binimetinib, i-bemetinib) |
| Iqembu lokulawula | I-Erbitux (cetuximab, cetuximab) |
| Iqembu lokulawula | I-Irinotecan noma i-FOLFIRI (i-folinic acid, i-fluorouracil ne-irinotecan) |
Imiphumela yocwaningo olukhulu
1. Ukusinda kweMedian (OS): Izinyanga ezingu-9.0 eqenjini lokwelapha kathathu
Izinyanga ezingu-8.4 eqenjini le-dual therapy
Iqembu lokulawula yizinyanga ezingu-5.4
2. Ukusinda ngaphandle kokuqhubekela phambili: Izinyanga ezi-4.3 eqenjini lokwelapha kathathu
Izinyanga ezi-4.2 zeqembu le-dual therapy
Iqembu lokulawula yizinyanga ezingu-1.5
3. Izinga lokusinda lezinyanga ezingu-6: 71% eqenjini lokwelapha kathathu
Ama-65% eqenjini le-dual therapy
Iqembu lokulawula lingu-47%
4. I-Objective Remission Rate (ORR): 26% eqenjini lokwelapha kathathu
Ama-20% eqenjini le-dual therapy
Iqembu lokulawula lingu-2%
Isithombe esingakwesokunxele siqhathanisa uhlobo lwezidakamizwa ezintathu ze-raftovi ne-OS yeqembu lokulawula, futhi isithombe esingakwesokudla siqhathanisa uhlobo lwezidakamizwa ezimbili ze-raftovi ne-OS yeqembu lokulawula.
Ngokuvamile, uma kuqhathaniswa nemithi yokwelapha ye-Erbitux kanye ne-irinotecan, ukusebenza kahle kohlobo lwemithi emibili kanye nemithi emithathu akuhlukile kakhulu, futhi kunemiphumela emibi embalwa yomtholampilo.
Umphenyi Omkhulu uDkt. Scott Kopetz uthe: “Njengesiguli esalashwe ngaphambilini i-BRAF V600E mutant metastatic colorectal cancer, i-Braftovi + Erbitux (conefinil + cetuximab) iwukwelashwa okuhlosiwe kokuqala Lena yindlela entsha yokwelapha iziguli ezinjalo eziyidinga kakhulu. “
Izimiso zokwelapha inhlanganisela ye-Braftovi nezinkomba
Braftovi’s active pharmaceutical ingredient ibinimetinib 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.
E-United States, inhlanganisela ye-Braftovi + Mektovi igunyazelwe i-melanoma engabukeki noma ye-metastatic enezinguquko ze-BRAF V600E noma ze-BRAF V600K. I-Braftovi ayilungele ukwelashwa kwe-melanoma yohlobo lwasendle lwe-BRAF. E-Europe, inhlanganisela ivunyiwe kubantu abadala abane-melanoma engabukeki noma ye-metastatic enokuguqulwa kwe-BRAF V600. E-Japan, inhlanganisela igunyazwe i-BRAF-mutated unresecable melanoma.
| Igama lesiNgisi | Igama lesiShayina | Target | nomakhi | Izinkomba | Medicare |
| I-Trametinib (Mekinist) | I-Trametinib | Mek | I-Novartis (ngaphandle) | Kuyafana nangaphezulu | cha |
| I-Vemurafenib (Zelboraf) | I-Verofinil (i-Verofinil, i-Zuobofu) | I-BRAF | I-Roche Gold neSilver Tektronix (ngaphandle) | I-Melanoma | Yebo, ifakiwe kumshwalense wezempilo |
| I-Cobimetinib (i-Cotellic) | I-Cobitinib | Mek | I-Roche Gold neSilver Tektronix (ngaphandle) | Kuyafana nangaphezulu | cha |
| I-Encorafenib (i-Braftovi) | I-Connefini | I-BRAF | I-Array BioPharma | I-Melanoma | cha |
| I-Binimetinib (Mektovi) | I-Bemetinib | Mek | I-Array BioPharma | Kuyafana nangaphezulu | cha |
Imihlahlandlela ye-NCCN ka-2019 ye-Colorectal Cancer ingeza izindlela zokwelapha ezintsha ezimbili ze-EGFR / BRAF / MEK ezintathu ze-inhibitor ezigulini ezinesifo esithuthukisiwe se-BRAF V600E esiguquguqukayo esithuthukisiwe, okuyilezi:
[1] I-Dabrafenib + Trametinib + Cetuximab / Panitumumab (Cetuximab / Panitumumab)
[2] I-Encorafenib (conefinil) + Binimetinib (bimetinib) + Cetuximab / Panitumumab (cetuximab / panitumumab)
UXiaobian unokuthile afuna ukukusho
Esikhathini sokwelashwa okuqondisiwe, sonke isiguli esinomdlavuza we-colorectal kufanele siphumelele ukutholwa kwe-MSI, ukuhlaziya ukuguqulwa kwe-RAS ne-BRAF, futhi senze i-HER2 amplification, NTRK nokunye ukutholwa kofuzo ngangokunokwenzeka. Ukuhlolwa kofuzo (NGS) kuzofakwa enkulumweni enkulu Izinga lokuhlola lokuqala leziguli eziningi. Abangane bomdlavuza abahlolelwe ulibofuzo bangathumela umbiko emnyangweni wezokwelapha ukuze uhunyushwe ukuze babone ukuthi ikhona yini indlela yokwelapha efanele.
Umhleli ukholelwa ukuthi esikhathini esizayo kuzoba nenqubekelaphambili yocwaningo lwakamuva kanye nemithi engcono kakhulu yomdlavuza we-colorectal. Ochwepheshe abaphezulu bomdlavuza kuphela ekhaya naphesheya abanokuhlangenwe nakho okucebile kwezokwelapha. Iziguli ezinomdlavuza we-colorectal zingafaka isicelo sokugunyazwa ngokubonisana nochwepheshe be-Global Oncologist Network, zithole uhlelo olungcono kakhulu lokuxilonga kanye nokwelashwa.
