Julij 2022: Dabrafenib (Tafinlar, Novartis) in trametinib (Mekinist, Novartis) prejelo pospešeno odobritev Uprave za hrano in zdravila za zdravljenje odraslih in pediatričnih bolnikov, starejših od 6 let, z neoperabilnimi ali metastatskimi solidnimi tumorji z mutacijo BRAF V600E, ki so napredovali po predhodnem zdravljenju in nimajo drugih ustreznih možnosti zdravljenja. Pri posameznikih s kolorektalnim rakom dabrafenib in trametinib nista priporočljiva zaradi znane intrinzične odpornosti na zaviranje BRAF. Bolnikom s solidnimi tumorji divjega tipa BRAF ni priporočljivo jemati dabrafeniba.
Za vrednotenje varnost in učinkovitost (študije v melanoma 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 kolorektalnega raka, 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 gliomi 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.
Pri odraslih bolnikih so se najpogosteje (20 %) pojavili zvišana telesna temperatura, utrujenost, slabost, izpuščaj, mrzlica, glavobol, krvavitev, kašelj, bruhanje, zaprtje, driska, mialgija, artralgija in edem.
Med pediatričnimi bolniki so bili najpogostejši neželeni učinki pireksija, izpuščaj, bruhanje, izčrpanost, suha koža, kašelj, driska, akneiformni dermatitis, glavobol, bolečine v trebuhu, slabost, krvavitev, zaprtje in paronihija (20 %).
Odrasli bolniki morajo jemati 2 mg trametiniba peroralno enkrat na dan skupaj s 150 mg (dvema 75-mg kapsulama) dabrafeniba dvakrat na dan. Glede na telesno maso morajo pediatrični bolniki jemati trametinib in dabrafenib v ustreznih odmerkih. Za bolnike, ki tehtajo manj kot 26 kg, ni določenega odmerka.
View full prescribing information for Tafinlar and Mekinist
