Initial US Approval

  • 20181

Indications

Unresectable Metastatic Melanoma:

  • In combination with binimetinib, for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test.1-2

Metastatic Colorectal Cancer:

  • In combination with cetuximab, for the treatment of adult patients with metastatic colorectal cancer (CRC) with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy.1-2

Metastatic NSCLC:

  • In combination with binimetinib, for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, as detected by an FDA-approved test.1-2

*Limitations of Use:

  • Encorafenib is not indicated for treatment of patients with wild-type BRAF melanoma, wild-type BRAF CRC, or wild-type BRAF NSCLC.

Recommended Dose/Route

  • In adult patients, encorafenib 450 mg (six 75 mg capsules) orally once daily in combination with binimetinib 45 mg orally taken twice daily, approximately 12 hours apart.1,2
Figure

Pivotal Study

PHAROS (NCT03915951)3

  • Key Inclusion Criteria: Eligible patients had a diagnosis of histologically-confirmed metastatic NSCLC with BRAF V600E mutation that was treatment-naïve or had been previously treated with 1 prior line of systemic therapy in the metastatic setting (platinum-based chemotherapy and/or anti-PD-1/PD-L1 therapies), an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, and measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.1,2 
  • Treatment: Encorafenib 450 mg once daily and binimetinib 45 mg orally twice daily until disease progression or unacceptable toxicity.1,2 
Figure

Safety

PHAROS3

  • Common Adverse Reactions: The most frequently reported any grade adverse events (AEs) were fatigue (61%), nausea (58%), diarrhea 52%), musculoskeletal pain (48%), vomiting (37%), abdominal pain (32%), visual impairment (29%), constipation (27%), dyspnea (27%), rash (27%), and cough (26%).1,2
  • Common Laboratory Abnormalities: The most frequently reported any grade laboratory abnormalities were increased creatine (91%), hyperglycemia (48%), anemia (47%), increased creatine kinase (41%), increased lipase (40%), increased ALT (31%), increased alkaline phosphatase (31%), hyperkalemia (31%), hyponatremia (26%), and lymphopenia (24%).1,2
  • Dosage Interruption Due to AEs: 59% (ENC), 62% (BIN)1,2
  • Dosage Reductions Due to AEs: 30% (ENC), 33% (BIN)1,2
  • Permanent Discontinuation Due to AEs: 16% (ENC), 17% (BIN)1,2
Figure

References

  1. BRAFTOVI (encorafenib). Prescribing information. Array BioPharma, Inc., 2023. https://labeling.pfizer.com/ShowLabeling.aspx?id=12990
  2. MEKTOVI (binimetinib). Prescribing information. Array BioPharma, Inc., 2023. https://labeling.pfizer.com/ShowLabeling.aspx?id=12988
  3. Riely GJ, Smit EF, Ahn MJ, et al. Phase II, open-label study of encorafenib plus binimetinib in patients with BRAF V600-mutant metastatic non-small-cell lung cancer. J Clin Oncol. 2023;41(21):3700-3711. doi: 10.1200/JCO.23.00774
  4. Baik C, Cheng ML, Dietrich M, Gray JE, Karim NA. A practical review of encorafenib and binimetinib therapy management in patients with BRAF V600E-mutant metastatic non-small cell lung cancer. Adv Ther. 2024;41(7):2586-2605. doi:10.1007/s12325-024-02839-4