Juli 2022: Dabrafenib (Tafinlar, Novartis) og trametinib (Mekinist, Novartis) mottatt akselerert godkjenning fra Food and Drug Administration for behandling av voksne og pediatriske pasienter eldre enn 6 år med uoperable eller metastatiske solide svulster med BRAF V600E-mutasjonen som har utviklet seg etter å ha mottatt tidligere behandling og ikke har andre passende behandlingsalternativer. For personer med tykktarmskreft anbefales ikke dabrafenib og trametinib på grunn av kjent iboende resistens mot BRAF-hemming. Pasienter med solide svulster som er BRAF vill-type anbefales ikke å ta 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 melanom 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 tykktarmskreft, 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 hjernesvulst 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.
Voksne pasienter hadde pyreksi, tretthet, kvalme, utslett, frysninger, hodepine, blødninger, hoste, oppkast, forstoppelse, diaré, myalgi, artralgi og ødem (20 %).
Blant pediatriske pasienter var pyreksi, utslett, oppkast, utmattelse, tørr hud, hoste, diaré, dermatitis acneiform, hodepine, magesmerter, kvalme, blødninger, forstoppelse og paronyki de hyppigste bivirkningene (20 %).
Voksne pasienter bør ta trametinib 2 mg oralt én gang daglig sammen med 150 mg (to 75 mg kapsler) dabrafenib to ganger daglig. Basert på kroppsvekt bør pediatriske pasienter ta trametinib og dabrafenib i passende doser. For pasienter som veier mindre enn 26 kg er det ingen fastsatt dose.
View full prescribing information for Tafinlar and Mekinist
