Initial US Approval
20181
Indications
The combination of encorafenib (ENC) with binimetinib (BIN) is approved 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. This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR).1,2
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
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
Safety
The most common any grade adverse events (AEs) included 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%). 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 AEs1,2: 59% (ENC), 62% (BIN)
Dosage Reductions Due to AEs1,2: 30% (ENC), 33% (BIN)
Permanent Discontinuation Due to AEs1,2: 16% (ENC), 17% (BIN)
References
1. Array BioPharma, Inc. BRAFTOVI (Encorafenib). Package Insert. October 2023. https://labeling.pfizer.com/ShowLabeling.aspx?id=12990
2. Array BioPharma, Inc. MEKTOVI (Binimetinib). Package Insert. October 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