Initial US Approval

  • 20131,2

Indications

  • The treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test.1-2
  • The adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection.1-2
  • The treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test.1-2
  • The treatment of patients with locally advanced or metastatic anaplastic thyroid cancer (ATC) with BRAF V600E mutation and with no satisfactory locoregional treatment options.1-2
  • The treatment of adult and pediatric patients 1 year of age and older with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).1-2
  • The treatment of pediatric patients 1 year of age and older with low-grade glioma (LGG) with a BRAF V600E mutation who require systemic therapy.1-2
  • Limitations of Use: Dabrafenib is not indicated for treatment of patients with colorectal cancer because of known intrinsic resistance to BRAF inhibition. Dabrafenib is not indicated for treatment of patients with wildtype BRAF solid tumors.

Recommended Dose/Route

  • In adult patients, dabrafenib 150 mg orally twice daily and trametinib 2 mg orally once daily.1,2
Dabrafenib and Trametinib: Dose Reduction

Dabrafenib and Trametinib: Dose Reduction

Pivotal Study

  • Study BRF113928 (NCT01336634)3
  • Key Inclusion Criteria: Eligible patients had locally confirmed BRAF V600E mutation-positive metastatic NSCLC, no prior exposure to BRAF or MEK-inhibitor, and absence of EGFR mutation or ALK rearrangement (unless patients had progression on prior tyrosine kinase inhibitor therapy).1,2 Patients enrolled in Cohorts A and B were required to have received at least one previous platinum-based chemotherapy regimen for NSCLC with demonstrated disease progression but no more than 3 prior systemic regimens. Patients enrolled in Cohort C could not have received prior systemic therapy for metastatic NSCLC.1,2
  • Treatment: Patients in Cohort A received dabrafenib 150 mg twice daily. Patients in Cohorts B and C received dabrafenib 150 mg twice daily and trametinib 2 mg once daily.1,2
Dabrafenib: Efficacy Data

Dabrafenib: Efficacy Data

Safety

  • Common Adverse Reactions: The most frequently reported any grade adverse events (AEs) were pyrexia (55%), fatigue (51%), nausea (45%), vomiting (33%), diarrhea (32%), dry skin (31%), decreased appetite (29%), edema (28%), rash (28%), chills (23%), hemorrhage (23%), cough (22%), and dyspnea (20%).
  • Common Laboratory Abnormalities: The most frequently reported any grade laboratory abnormalities were hyperglycemia (71%), increased alkaline phosphatase (64%), increased AST (61%), hyponatremia (57%), leukopenia (48%), anemia (46%), neutropenia (44%), hypophosphatemia (36%), increased ALT (32%), and increased creatinine (21%).1,2
  • Dosage Interruption Due to AEs: 55% (DAB), 57% (TRA)1,2
  • Dosage Reductions Due to AEs: 44% (DAB), 30% (TRA)1,2
  • Permanent Discontinuation Due to AEs: 13% (DAB), 19% (TRA)1,2

References

  1. TAFINLAR (dabrafenib). Prescribing information. Novartis; 2024. https://www.novartis.com/us-en/sites/novartis_us/files/tafinlar.pdf
  2. MEKINST (trametinib). Prescribing information. Novartis; 2024. https://www.novartis.com/us-en/sites/novartis_us/files/mekinist.pdf
  3. Planchard D, Besse B, Groen HJM, et al. Phase 2 study of dabrafenib plus trametinib in patients with BRAF V600E-mutant metastatic NSCLC: updated 5-year survival rates and genomic analysis. J Thorac Oncol. 2022 Jan;17(1):103-115. doi: 10.1016/j.jtho.2021.08.011
  4. Chalmers A, Cannon L, Akerley W. Adverse event management in patients with BRAF V600E-mutant non-small cell lung cancer treated with dabrafenib plus trametinib. Oncologist. 2019;24(7):963-972. doi:10.1634/theoncologist.2018-0296
  5. Thawer A, Miller WH, Gregorio N, et al. Management of pyrexia associated with the combination of dabrafenib and trametinib: Canadian consensus statements. Curr Oncol. 2021;28(5):3537-3553. doi:10.3390/curroncol28050304