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  • BRAF-mutant metastatic mCRC is an area of high unmet need

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

    Patients with BRAF-mutant mCRC have a poor prognosis5,6

    Patients with mCRC harboring BRAF V600 mutations exhibited less than half the median overall survival of patients with wild-type BRAF mCRC7

    Patients with BRAF-mutant mCRC progressed about twice as fast on initial treatment as those patients with BRAF wild-type mCRC7

    • After initial treatment failure, subsequent lines of therapy have a minimal effect, and patients experience rapid disease progression and short survival5

    In a population-based cohort, about 1 out of 10 patients with BRAF-mutant mCRC received subsequent therapy after 2 lines of therapy8

    BRAFTOVI + cetuximab provides an actionable reason to test all patients with mCRC for a BRAF V600E mutation1,9,10

    With up to 15% of mCRC patients harboring a BRAF mutation, testing at diagnosis can inform a treatment plan​​​​​​​

    • Confirmation of a BRAF  V600E mutation with an FDA-approved test can help identify patients that may be eligible for targeted treatment with BRAFTOVI + cetuximab after prior therapy

    NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend testing all patients with mCRC for both BRAF and RAS mutations at diagnosis11,12

    mCRC, metastatic colorectal cancer; NCCN, National Comprehensive Cancer Network® (NCCN®).

    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. Kopetz S, Grothey A, Yaeger R, et al. N Engl J Med. 2019;381(17):1632-1643.
    6. Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27(8):1386-1422.
    7. Cremolini C, Loupakis F, Antoniotti C, et al. TRIBE study. Lancet Oncol. 2015;16(13):1306-1315.
    8. Chu JE, Johnson B, Kugathasan L, et al. Population-based screening for BRAF V600E in metastatic colorectal cancer reveals increased prevalence and poor prognosis. Clin Cancer Res. 2020;26(17):4599-4605.
    9. Loupakis F, Ruzzo A, Cremolini C, et al. KRAS codon 61, 146 and BRAF mutations predict resistance to cetuximab plus irinotecan in KRAS codon 12 and 13 wild-type metastatic colorectal cancer. Br J Cancer. 2009;101(4):715-721.
    10. Corcoran RB, Ebi H, Turke AB, et al. EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF-mutant colorectal cancers to RAF inhibition with vemurafenib. Cancer Discov. 2012;2(3):227-235.
    11. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Colon Cancer V.2.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed January 29, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
    12. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Rectal Cancer V.1.2021. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed January 29, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

    BRAF-mutant mCRC and MOA

    • Unmet need in BRAF-mutant mCRC
    • MOA

    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.​​​​​​​