• Prescribing Information
  • Medication Guide
  • Patient Site
  • Medical Information
  • Efficacy—Overall response rate/duration of response

    The first and only FDA-approved targeted therapy regimen for adults with previously treated mCRC with a BRAF V600E mutation1-4

    1 in 5 patients responded to treatment with BRAFTOVI + cetuximab

    Overall response rate (per BICR)1

    Confirmed responses per RECIST v1.1 assessed in the subset of the first 220 patients included in the randomized portion of the BRAFTOVI + cetuximab arm (n=113) and the FOLFIRI + cetuximab or irinotecan + cetuximab arm (n=107). ORR defined as CR (disappearance of all target lesions) + PR (≥30% decrease in target lesion size).1,5 

      aSD (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD) is not a component of ORR and can reflect the natural progression of disease rather than a direct therapeutic effect.6,7

      bDCR (CR + PR + SD + non-PD/non-CR*) may not be directly correlated to efficacy outcomes. DCR was not a prespecified analysis and no conclusion of statistical or clinical significance can be drawn.5

       *Patients with only nonmeasurable disease, whose best nontarget lesion response was non-PD/non-CR, and did not have any new lesions. This included 4 patients treated with BRAFTOVI + cetuximab and 5 patients treated with FOLFIRI + cetuximab or irinotecan + cetuximab.
    ​​​​​​​

    PD defined as ≥20% increase in target lesion size or the appearance of at least 1 new lesion.7

    Duration of response (per BICR)1,5​​​​​​​

    Median DoR for the 23 patients who responded to treatment with BRAFTOVI + cetuximab was 6.1 months (95% CI: 4.1-8.3) and was not reached (95% CI: 2.6-NR) for the 2 patients who responded to treatment with FOLFIRI + cetuximab or irinotecan + cetuximab.

    BICR, blinded independent central review; CR, complete response; DoR, duration of response; mCRC, metastatic colorectal cancer; NR, not reached; ORR, overall response rate; PD, progressive disease; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors.

    References:
    1. BRAFTOVI® (encorafenib) Prescribing Information. Array BioPharma, Inc.; April 2020.
    2. Erbitux® (cetuximab) Prescribing Information. Eli Lilly and Company; 2019.
    3. Center for Drug Evaluation and Research. Approved Drugs - Hematology/Oncology (Cancer) Approvals & Safety Notifications. Internet Archive Wayback Machine. Accessed March 6, 2020. http://wayback.archive-it.org/7993/20170111064250/http:/www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm279174.htm
    4. Center for Drug Evaluation and Research. Approved Drugs - Hematology/Oncology (Cancer) Approvals & Safety Notifications. US Food and Drug Administration. Accessed March 6, 2020. https://www.fda.gov/drugs/resources-information-approved-drugs/hematologyoncology-cancer-approvals-safety-notifications
    5. Data on file. Pfizer Inc.
    6. Kopetz S, Grothey A, Yaeger R, et al. [protocol]. N Engl J Med. 2019;381(17):1632-1643.
    7. Food and Drug Administration. Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics: Guidance for Industry. December 2018. Accessed September 24, 2020. https://www.fda.gov/media/71195/download

    Efficacy

    • Trial design

    • Select patient characteristics

    • Overall survival

    • Overall response rate/Duration of response
    • Progression-free survival

    Safety data for BRAFTOVI + cetuximab

    View

    WARNINGS AND PRECAUTIONS

    New Primary Malignancies, cutaneous and non-cutaneous, can occur with BRAFTOVI. In the BEACON CRC trial, cutaneous squamous cell carcinoma (cuSCC), including keratoacanthoma (KA), occurred in 1.4% of patients with CRC, and a new primary melanoma occurred in 1.4% of patients who received BRAFTOVI in combination with cetuximab. Perform dermatologic evaluations prior to initiating treatment, every 2 months during treatment, and for up to 6 months following discontinuation of treatment. Manage suspicious skin lesions with excision and dermatopathologic evaluation. Dose modification is not recommended for new primary cutaneous malignancies. Based on its mechanism of action, BRAFTOVI may promote malignancies associated with activation of RAS through mutation or other mechanisms. Monitor patients receiving BRAFTOVI for signs and symptoms of non-cutaneous malignancies. Discontinue BRAFTOVI for RAS mutation-positive non-cutaneous malignancies.

    Tumor Promotion in BRAF Wild-Type Tumors: In vitro experiments have demonstrated paradoxical activation of MAP-kinase signaling and increased cell proliferation in BRAF wild-type cells exposed to BRAF inhibitors. Confirm evidence of BRAF V600E or V600K mutation using an FDA-approved test prior to initiating BRAFTOVI. 

    Hemorrhage: In BEACON CRC, hemorrhage occurred in 19% of patients receiving BRAFTOVI in combination with cetuximab; Grade 3 or higher hemorrhage occurred in 1.9% of patients, including fatal gastrointestinal hemorrhage in 0.5% of patients. The most frequent hemorrhagic events were epistaxis (6.9%), hematochezia (2.3%), and rectal hemorrhage (2.3%). Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.

    Uveitis: Uveitis, including iritis and iridocyclitis, has been reported in patients treated with BRAFTOVI. Assess for visual symptoms at each visit. Perform an ophthalmological evaluation at regular intervals and for new or worsening visual disturbances, and to follow new or persistent ophthalmologic findings. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.

    QT Prolongation: BRAFTOVI is associated with dose-dependent QTc interval prolongation in some patients. Monitor patients who already have or who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, severe or uncontrolled heart failure and those taking other medicinal products associated with QT prolongation. Correct hypokalemia and hypomagnesemia prior to and during BRAFTOVI administration. Withhold, reduce dose, or permanently discontinue for QTc >500 ms.

    Embryo-Fetal Toxicity: BRAFTOVI can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with BRAFTOVI and for 2 weeks after the final dose. Advise females to contact their healthcare provider of a known or suspected pregnancy.

    Lactation: Advise women not to breastfeed during treatment with BRAFTOVI and for 2 weeks after the final dose.

    Infertility: Advise males of reproductive potential that BRAFTOVI may impair fertility.

    Risks Associated with Combination Treatment: BRAFTOVI is indicated for use as part of a regimen in combination with cetuximab. Refer to the prescribing information for cetuximab for additional risk information.​​​​​​​

    ADVERSE REACTIONS

    The most common adverse reactions (≥25%, all grades) in the BRAFTOVI with cetuximab arm compared to irinotecan with cetuximab or FOLFIRI with cetuximab (control) were: fatigue (51% vs 50%), nausea (34% vs 41%), diarrhea (33% vs 48%), dermatitis acneiform (32% vs 43%), abdominal pain (30% vs 32%), decreased appetite (27% vs 27%), arthralgia (27% vs 3%), and rash (26% vs 26%). Other clinically important adverse reactions occurring in <10% of patients who received BRAFTOVI in combination with cetuximab was pancreatitis.

    The most common laboratory abnormalities (≥20%, all grades) in the BRAFTOVI with cetuximab arm compared to irinotecan with cetuximab or FOLFIRI with cetuximab (control) were: anemia (34% vs 48%) and lymphopenia (24% vs 35%).

    DRUG INTERACTIONS

    Avoid coadministration of BRAFTOVI with strong or moderate CYP3A4 inhibitors (including grapefruit juice) or CYP3A4 inducers and use caution with sensitive CYP3A4 substrates. Modify BRAFTOVI dose if coadministration with a strong or moderate CYP3A4 inhibitor cannot be avoided. Avoid coadministration of BRAFTOVI with drugs known to prolong QT/QTc interval or hormonal contraceptives.

    Refer to the cetuximab prescribing information for recommended dosing and safety information.
    ​​​​​​​Please see full Prescribing Information including Medication Guide for BRAFTOVI.

    BRAFTOVI® (encorafenib) is indicated, 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.

    Limitations of Use: BRAFTOVI is not indicated for treatment of patients with wild-type BRAF CRC. 

    INDICATION AND USAGE

    BRAFTOVI® (encorafenib) is indicated, 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. 

    Limitations of Use: BRAFTOVI is not indicated for treatment of patients with wild-type BRAF CRC.​​​​​​​