Juli xnumx: Dabrafenib (Tafinlar, Novartis) , trametinib (Mekinist, Novartis) modtaget accelereret godkendelse fra Food and Drug Administration til behandling af voksne og pædiatriske patienter ældre end 6 år med inoperable eller metastatiske solide tumorer med BRAF V600E-mutationen, som har udviklet sig efter at have modtaget tidligere behandling og ikke har andre egnede behandlingsmuligheder. Til personer med kolorektal cancer anbefales dabrafenib og trametinib ikke på grund af kendt iboende resistens over for BRAF-hæmning. Patienter med solide tumorer, der er BRAF-vildtype, anbefales ikke at tage 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 kolorektal cancer, 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 gliomer 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 patienter havde pyreksi, træthed, kvalme, udslæt, kulderystelser, hovedpine, blødning, hoste, opkastning, forstoppelse, diarré, myalgi, artralgi og ødemer (20%).
Blandt pædiatriske patienter var pyreksi, udslæt, opkastning, udmattelse, tør hud, hoste, diarré, dermatitis acneiform, hovedpine, mavesmerter, kvalme, blødninger, forstoppelse og paronychia de hyppigste bivirkninger (20%).
Voksne patienter bør tage trametinib 2 mg oralt én gang dagligt sammen med 150 mg (to 75 mg kapsler) dabrafenib to gange dagligt. Baseret på kropsvægt bør pædiatriske patienter tage trametinib og dabrafenib i passende doser. For patienter, der vejer mindre end 26 kg, er der ingen fast dosis.
View full prescribing information for Tafinlar and Mekinist
