Julie 2022: Dabrafenib (Tafinlar, Novartis) en trametinib (Mekinist, Novartis) het versnelde goedkeuring van die Food and Drug Administration ontvang vir die behandeling van volwasse en pediatriese pasiënte ouer as 6 jaar oud met nie-opereerbare of metastatiese soliede gewasse met die BRAF V600E mutasie wat gevorder het nadat hulle vorige terapie ontvang het en geen ander geskikte behandelingsopsies het nie. Vir individue met kolorektale kanker word dabrafenib en trametinib nie aanbeveel nie as gevolg van bekende intrinsieke weerstand teen BRAF-inhibisie. Pasiënte met soliede gewasse wat BRAF-wildtipe is, word nie aanbeveel om dabrafenib te neem nie.
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 melanoom 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 kolorektale kanker, 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 gliome 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.
Volwasse pasiënte het die meeste pyreksie, moegheid, naarheid, uitslag, kouekoors, hoofpyn, bloeding, hoes, braking, hardlywigheid, diarree, mialgie, artralgie en edoem (20%).
Onder pediatriese pasiënte was pyreksie, uitslag, braking, uitputting, droë vel, hoes, diarree, akneevormende dermatitis, hoofpyn, maagpyn, naarheid, bloeding, hardlywigheid en paronichie die mees algemene newe-effekte (20%).
Volwasse pasiënte moet trametinib 2 mg een keer per dag oraal neem saam met 150 mg (twee 75 mg kapsules) dabrafenib twee keer per dag. Gebaseer op liggaamsgewig, moet pediatriese pasiënte trametinib en dabrafenib teen die toepaslike dosisse neem. Vir pasiënte wat minder as 26 kg weeg, is daar geen vasgestelde dosis nie.
View full prescribing information for Tafinlar and Mekinist
