Julho 2022: Dabrafenibe (Tafinlar, Novartis) e trametinibe (Mekinist, Novartis) recebeu aprovação acelerada da Food and Drug Administration para o tratamento de pacientes adultos e pediátricos com mais de 6 anos de idade com tumores sólidos irressecáveis ou metastáticos com a mutação BRAF V600E que progrediram após receber terapia anterior e não têm outras opções de tratamento adequadas. Para indivíduos com câncer colorretal, dabrafenibe e trametinibe não são recomendados devido à conhecida resistência intrínseca à inibição de BRAF. Pacientes com tumores sólidos que são do tipo BRAF selvagem não são recomendados para tomar dabrafenibe.
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 câncer colorretal, 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 gliomas 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.
Os pacientes adultos apresentaram pirexia, cansaço, náusea, erupção cutânea, calafrios, dor de cabeça, sangramento, tosse, vômito, constipação, diarreia, mialgia, artralgia e edema com maior frequência (20%).
Entre os pacientes pediátricos, pirexia, erupção cutânea, vômito, exaustão, pele seca, tosse, diarreia, dermatite acneiforme, dor de cabeça, dor de estômago, náusea, hemorragia, constipação e paroníquia foram os efeitos colaterais mais frequentes (20%).
Pacientes adultos devem tomar trametinibe 2 mg por via oral uma vez ao dia juntamente com 150 mg (duas cápsulas de 75 mg) de dabrafenibe duas vezes ao dia. Com base no peso corporal, os doentes pediátricos devem tomar trametinib e dabrafenib nas doses adequadas. Para pacientes que pesam menos de 26 kg, não há dose definida.
View full prescribing information for Tafinlar and Mekinist
