Initial US Approval

  • Dabrafenib, 20131; trametinib, 20132; dabrafenib plus trametinib for advanced solid tumors including gastric cancer, 2022.3

Indications

  • The treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test.1
  • The treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test.1
  • 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
  • The treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test.1
  • 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
  • The treatment of adult and pediatric patients 1 year and older with unresectable or metastatic solid tumors with BRAF V600E mutation and 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 and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).1-3
  • 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, given orally twice daily and trametinib, 2 mg, given orally once daily.1,2,4
Dose Reductions for Adverse Reactions with Dabrafenib and Trametinib

Dose Reductions for Adverse Reactions with Dabrafenib and Trametinib

Pivotal Study

  • The MATCH Screening Trial (NCT02465060), subprotocol H5
  • Key Inclusion Criteria: Eligible patients could have any solid tumor that had progressed with standard therapy or that had no known curative treatment available; they needed to have an ECOG performance status of 0 or 1 and adequate kidney, liver, and hematopoietic function. Subprotocol H–eligible patients had a BRAF V600E mutation confirmed based on central MATCH assay or next-generation sequencing confirmed by central assay.5-7
  • Treatment: Dabrafenib, 150 mg, given twice daily and trametinib, 2 mg, given once daily in continuous 28-day cycles until disease progression, intolerable toxicity, or study withdrawal occurred.5
Dabrafenib and Trametinib: Efficacy Data

Dabrafenib and Trametinib: Efficacy Data

Safety

  • Common Adverse Reactions (≥20%): The most frequently reported any grade AEs were pyrexia (55%), fatigue (50%), nausea (40%), rash (40%), chills (30%), headache (30%), hemorrhage (29%), cough (29%), constipation (27%), vomiting (27%), diarrhea (26%), myalgia (24%), arthralgia (23%), and peripheral edema (22%).1,2,8
  • Common Laboratory Abnormalities (≥20%): The most frequently reported laboratory abnormalities were hyperglycemia (61%), increased alkaline phosphatase (51%), increased AST (51%), increased ALT (39%), and decreased hemoglobin (44%), decreased sodium (35%), decreased magnesium (24%), increased creatinine (21%).1,2,8
  • Dosage Interruption Due to Adverse Events (AEs): 55%1,2,8
  • Dosage Reductions Due to AEs: 44%1,2,8
  • Permanent Discontinuation Due to AEs: 13%1,2,8

References

  1. TAFINLAR. Prescribing information. Novartis; 2024. Accessed March 11, 2024. https://www.novartis.com/us-en/sites/novartis_us/files/tafinlar.pdf
  2. MEKINIST. Prescribing information. Novartis; 2024. Accessed March 11, 2024. https://www.novartis.com/us-en/sites/novartis_us/files/mekinist.pdf
  3. Winstead E. Dabrafenib-trametinib combination approved for solid tumors with BRAF mutations. American Cancer Society. July 21, 2022. Accessed March 9, 2024. https://www.cancer.gov/news-events/cancer-currents-blog/2022/fda-dabrafenib-trametinib-braf-solid-tumors
  4. NCCN. Clinical Practice Guidelines in Oncology. Pancreatic adenocarcinoma, version 1.2024. Accessed March 11, 2024. nccn.org/professionals/physician_gls/pdf/gastric.pdf
  5. Salama AKS, Li S, Macrae ER, et al. Dabrafenib and trametinib in patients with tumors with BRAF V600E mutations: Results of the NCI-MATCH trial subprotocol H. J Clin Oncol. 2020;38(33):3895-3904. doi:10.1200/JCO.20.00762
  6. Vrooman Durning M. NCI-MATCH trial explores tumor-agnostic approach. Targeted Oncology. February 3, 2021. Accessed March 10, 2024. https://www.targetedonc.com/view/nci-match-trial-explores-tumor-agnostic-approach
  7. Targeted therapy directed by genetic testing in treating patients with advanced refractory solid tumors, lymphomas, or multiple myeloma (The MATCH Screening Trial). National Cancer Institute. Accessed March 10, 2024. https://www.cancer.gov/research/participate/clinical-trials-search/v?id=NCT02465060&r=1
  8. Subbiah V, Kreitman RJ, Wainberg ZA, et al. Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial. Nat Med. 2023;29(5):1103-1112. doi:10.1038/s41591-023-02321-8