Julai 2022: Dabrafenib (Tafinlar, Novartis) and trametinib (Mekinist, Novartis) menerima kelulusan dipercepatkan daripada Pentadbiran Makanan dan Ubat-ubatan untuk rawatan pesakit dewasa dan kanak-kanak berumur lebih dari 6 tahun dengan tumor pepejal yang tidak boleh direseksi atau metastatik dengan mutasi BRAF V600E yang telah berkembang selepas menerima terapi terdahulu dan tidak mempunyai pilihan rawatan lain yang sesuai. Bagi individu yang menghidap kanser kolorektal, dabrafenib dan trametinib tidak disyorkan kerana rintangan intrinsik yang diketahui terhadap perencatan BRAF. Pesakit dengan tumor pepejal yang jenis liar BRAF tidak disyorkan untuk mengambil 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 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 kanser kolorektal, 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.
Pesakit dewasa mengalami pyrexia, keletihan, loya, ruam, menggigil, sakit kepala, pendarahan, batuk, muntah, sembelit, cirit-birit, myalgia, arthralgia, dan edoema paling kerap (20%).
Di kalangan pesakit kanak-kanak, pyrexia, ruam, muntah, keletihan, kulit kering, batuk, cirit-birit, dermatitis acneiform, sakit kepala, sakit perut, loya, pendarahan, sembelit, dan paronychia adalah kesan sampingan yang paling kerap (20%).
Pesakit dewasa perlu mengambil trametinib 2 mg secara lisan sekali sehari bersama-sama dengan 150 mg (dua kapsul 75 mg) dabrafenib dua kali sehari. Berdasarkan berat badan, pesakit kanak-kanak harus mengambil trametinib dan dabrafenib pada dos yang sesuai. Bagi pesakit yang mempunyai berat badan kurang daripada 26 kg, tiada dos yang ditetapkan.
View full prescribing information for Tafinlar and Mekinist
