Srpanj 2022: Dabrafenib (Tafinlar, Novartis) i trametinib (Mekinist, Novartis) dobio je ubrzano odobrenje od Uprave za hranu i lijekove za liječenje odraslih i pedijatrijskih pacijenata starijih od 6 godina s neoperabilnim ili metastatskim čvrstim tumorima s mutacijom BRAF V600E koji su napredovali nakon primanja prethodne terapije i nemaju druge odgovarajuće mogućnosti liječenja. Za osobe s kolorektalnim rakom, dabrafenib i trametinib se ne preporučuju zbog poznate intrinzične otpornosti na inhibiciju BRAF-a. Bolesnicima sa solidnim tumorima divljeg tipa BRAF ne preporučuje se uzimanje dabrafeniba.
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 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 Rak debelog crijeva, 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.
Odrasli su bolesnici najčešće (20%) imali povišenu temperaturu, umor, mučninu, osip, zimicu, glavobolju, krvarenje, kašalj, povraćanje, konstipaciju, proljev, mijalgiju, artralgiju i edem.
Među pedijatrijskim pacijentima najčešće su nuspojave (20%) bile pireksija, osip, povraćanje, iscrpljenost, suha koža, kašalj, proljev, akneiformni dermatitis, glavobolja, bolovi u trbuhu, mučnina, krvarenje, zatvor i paronihija.
Odrasli bolesnici trebaju uzimati trametinib 2 mg peroralno jednom dnevno zajedno sa 150 mg (dvije kapsule od 75 mg) dabrafeniba dva puta dnevno. Na temelju tjelesne težine, pedijatrijski bolesnici trebaju uzimati trametinib i dabrafenib u odgovarajućim dozama. Za pacijente manje od 26 kg nema određene doze.
View full prescribing information for Tafinlar and Mekinist
