Júlí 2022: Dabrafenib (Tafinlar, Novartis) og trametinib (Mekinist, Novartis) fengið flýtisamþykki Matvæla- og lyfjaeftirlitsins til meðferðar á fullorðnum og börnum eldri en 6 ára með óskurðtæk æxli eða æxli með meinvörpum með BRAF V600E stökkbreytingu sem hafa þróast eftir að hafa fengið fyrri meðferð og hafa enga aðra viðeigandi meðferðarmöguleika. Fyrir einstaklinga með ristilkrabbamein er ekki mælt með dabrafenib og trametinibi vegna þekktrar innra ónæmis gegn BRAF hömlun. Ekki er mælt með því að sjúklingar með fast æxli sem eru af BRAF villigerð taki dabrafenib.
36 paediatric patients from CTMT212X2101 (NCT02124772), 131 adult patients from open-label, multiple cohort trials BRF117019 (NCT02034110) and NCI-MATCH (NCT02465060), and results from COMBI-d, COMBI-v, and BRF113928 were used to evaluate the safety and efficacy (studies in sortuæxli and lung cancer already described in product labeling). Patients with certain solid tumours, such as high grade glioma (HGG), biliary tract cancer, low grade glioma (LGG), small intestinal adenocarcinoma, gastrointestinal stromal tumour, and anaplastic thyroid cancer, that are positive for the BRAF V600E mutation were enrolled in the study BRF117019 (ATC). Except for patients with melanoma, thyroid cancer, or Ristilkrabbamein, NCI-MATCH Subprotocol H recruited adult patients with BRAF V600E mutation positive solid tumours. A total of 36 paediatric patients with BRAF V600 refractory or recurrent LGG or HGG were included in Parts C and D of Study CTMT212X2101. The overall response rate (ORR) utilising conventional response criteria served as the trials’ primary efficacy outcome measure. A total of 54 (41 percent, 95 percent CI: 33, 50) of the 131 adult patients showed an objective response. Patients with 24 distinct tumour types, including several subtypes of LGG and HGG, were enrolled in the study. Among the most prevalent tumour forms, the ORR for biliary tract cancer was 46% (95% CI: 31, 61), for combined high grade glioma it was 33% (95% CI: 20, 48), and for low grade gliomas it was 50% (95% CI: 23, 77). (combined). The ORR for the 36 paediatric patients was 25% (95% CI: 12, 42); the DOR was 6 months or less for 78 percent of patients and 24 months or less for 44 percent.
Fullorðnir sjúklingar voru oftast með hita, þreytu, ógleði, útbrot, kuldahroll, höfuðverk, blæðingu, hósta, uppköst, hægðatregðu, niðurgang, vöðvabólgu, liðverki og bjúg (20%).
Meðal barnasjúklinga voru hiti, útbrot, uppköst, þreyta, þurr húð, hósti, niðurgangur, húðbólga unglingabólur, höfuðverkur, magaverkir, ógleði, blæðingar, hægðatregða og ofsakláði algengustu aukaverkanirnar (20%).
Fullorðnir sjúklingar ættu að taka trametinib 2 mg til inntöku einu sinni á dag ásamt 150 mg (tvö 75 mg hylki) af dabrafenib tvisvar á dag. Miðað við líkamsþyngd ættu börn að taka trametinib og dabrafenib í viðeigandi skömmtum. Fyrir sjúklinga sem vega minna en 26 kg er enginn ákveðinn skammtur.
View full prescribing information for Tafinlar and Mekinist
