Learn about a treatment option for your eligible patients
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INDICATION AND USAGE
BRAFTOVI® (encorafenib) and MEKTOVI® (binimetinib) are kinase inhibitors indicated for use in combination 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.
Limitations of Use: BRAFTOVI is not indicated for treatment of patients with wild-type BRAF NSCLC.
SELECT IMPORTANT SAFETY INFORMATION
• Use of BRAFTOVI + MEKTOVI is associated with the following WARNINGS and PRECAUTIONS: New Primary Malignancies, Tumor Promotion in BRAF Wild-Type Tumors, Cardiomyopathy, Hepatotoxicity, Rhabdomyolysis, Hemorrhage, Venous Thromboembolism, Ocular Toxicities, QT Prolongation, Interstitial Lung Disease, Embryo-Fetal Toxicity, Risks Associated with BRAFTOVI as a Single Agent, and Risks Associated with Combination Treatment1,2
The information below applies to the safety of the combination of BRAFTOVI and MEKTOVI unless otherwise noted. See full Prescribing Information for BRAFTOVI and for MEKTOVI for dose modifications for adverse reactions.
New Primary Malignancies:
New primary malignancies, cutaneous and non-cutaneous, can occur. In the PHAROS trial, cutaneous squamous cell carcinoma (cuSCC) and skin papilloma (SP), each occurred in 2% of patients. 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. Monitor patients for new malignancies prior to initiation of treatment, while on treatment, and after discontinuation of treatment.
Please see additional Important Safety Information below. |
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Encorafenib (BRAFTOVI®) in combination with binimetinib (MEKTOVI®) is a preferred first-line therapy option NCCN Category 2A for patients with metastatic NSCLC with a BRAF V600E mutation in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®).3*
*Category 2A: Based upon lower-level evidence, there is uniform NCCN consensus (≥85% support of the Panel) that the intervention is appropriate. |
Results from the PHAROS trial1,2,4
PHAROS is a phase 2, open-label, multicenter, single-arm clinical trial of BRAFTOVI + MEKTOVI in 98 patients (treatment-naïve, n=59; previously treated, n=39) with BRAF V600E mutation-positive metastatic NSCLC. Prior use of BRAF inhibitors or MEK inhibitors was not allowed. Patients received BRAFTOVI 450 mg orally once daily and MEKTOVI 45 mg orally twice daily until disease progression or unacceptable toxicity. The major efficacy outcome measures were objective response rate (ORR) per RECIST v1.1 and duration of response (DoR) as assessed by independent radiology review (IRR).
Major efficacy outcome measure: Primary analysis of ORR per RECIST v1.1 by IRR1,2,4† |
†ORR based on September 22, 2022, data cutoff.4
‡Based on observed duration of response.1,2
§DoR based on April 1, 2024, data cutoff.5 |
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Select safety profile from the PHAROS trial1,2 | |
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Use of BRAFTOVI + MEKTOVI is associated with the following WARNINGS and PRECAUTIONS: New Primary Malignancies, Tumor Promotion in BRAF Wild-Type Tumors, Cardiomyopathy, Hepatotoxicity, Rhabdomyolysis, Hemorrhage, Venous Thromboembolism, Ocular Toxicities, QT Prolongation, Interstitial Lung Disease, Embryo-Fetal Toxicity, Risks Associated with BRAFTOVI as a Single Agent, and Risks Associated with Combination Treatment1,2 |
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Serious ARs occurred in 38% of patients who received BRAFTOVI + MEKTOVI. Serious ARs occurring in ≥2% of patients were hemorrhage (6%), diarrhea (4.1%), anemia (3.1%), dyspnea (3.1%), pneumonia (3.1%), arrhythmia (2%), device related infection (2%), edema (2%), myocardial infarction (2%), and pleural effusion (2%)1,2 |
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Fatal ARs occurred in 2% of patients who received BRAFTOVI + MEKTOVI, including intracranial hemorrhage (1%) and myocardial infarction (1%)1,2 |
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The most common ARs (≥25%) 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 | |
ARs occurring in ≥10% of patients receiving BRAFTOVI + MEKTOVI1,2¶# |
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Other clinically important ARs occurring in <10% of patients who received BRAFTOVI + MEKTOVI were peripheral neuropathy, dysgeusia, facial paresis, pancreatitis, hyperkeratosis, erythema, photosensitivity, and drug hypersensitivity1,2 |
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22% of patients (n=22/98) receiving BRAFTOVI + MEKTOVI experienced pyrexia (Grade 1: 20% [n=20/98]; Grade 2: 2% [n=2/98])1,2,5# | |
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All events of pyrexia were Grade 1 or 2 in severity, and none led to treatment discontinuation1,2,4 | |
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ARs leading to dose interruptions, dose reductions, or permanent discontinuation of BRAFTOVI1¶ |
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Dose interruptions of BRAFTOVI occurred in 59% of patients receiving BRAFTOVI | |
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The most common ARs (≥5%) leading to dose interruptions were diarrhea (17%), nausea (13%), musculoskeletal pain, fatigue (8% each), AST increased (7%), ALT increased, anemia, hemorrhage, vomiting (6% each), and acute kidney injury (5%) | |
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Dose reductions of BRAFTOVI occurred in 30% of patients receiving BRAFTOVI | |
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The most common ARs (≥5%) leading to dose reductions were diarrhea, nausea (8% each), AST increased, and fatigue (5% each) | |
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Permanent discontinuation of BRAFTOVI occurred in 16% of patients receiving BRAFTOVI | |
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The most common ARs (≥2%) leading to permanent discontinuation were diarrhea, musculoskeletal pain (3.1% each), fatigue, vomiting, nausea, rash, and visual impairment (2% each) |
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None of the other ARs leading to permanent discontinuation of BRAFTOVI occurred in more than 1 patient | |
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ARs leading to dose interruptions, dose reductions, or permanent discontinuation of MEKTOVI2¶ |
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Dose interruptions of MEKTOVI occurred in 62% of patients receiving MEKTOVI | |
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The most common ARs (≥5%) leading to dose interruptions were diarrhea (17%), nausea (15%), fatigue (9%), AST increased (7%), ALT increased, anemia, musculoskeletal pain, vomiting (6% each), acute kidney injury, hemorrhage, and LV dysfunction/cardiomyopathy (5% each) | |
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Dose reductions of MEKTOVI occurred in 33% of patients receiving MEKTOVI | |
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The most common ARs (≥5%) leading to dose reductions were diarrhea (8%), nausea (6%), and AST increased (5%) | |
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Permanent discontinuation of MEKTOVI occurred in 17% of patients receiving MEKTOVI | |
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The most common ARs (≥2%) leading to permanent discontinuation were diarrhea (3.1%), musculoskeletal pain, LV dysfunction/cardiomyopathy, fatigue, nausea, rash, visual impairment, and vomiting (2% each) |
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None of the other ARs leading to permanent discontinuation of MEKTOVI occurred in more than 1 patient | |
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¶Based on September 22, 2022, data cutoff.4
#Grades per National Cancer Institute CTCAE v.4.03.1,2
||One Grade 5 AR of hemorrhage occurred.1,2
**Composite term: Fatigue includes fatigue, asthenia; diarrhea includes diarrhea, colitis; musculoskeletal pain includes back pain, musculoskeletal pain, pain in extremity, myalgia, non-cardiac chest pain, neck pain; abdominal pain includes abdominal pain, abdominal pain upper, abdominal discomfort, epigastric discomfort; visual impairment includes vision blurred, visual impairment, vitreous floaters, photophobia, visual acuity reduced, photopsia; dyspnea includes dyspnea, dyspnea exertional; rash includes dermatitis acneiform, eczema, palmar-plantar erythrodysesthesia syndrome, rash, rash macular, rash maculo-papular, rash papular, rash pustular, skin exfoliation; cough includes cough, productive cough; edema includes edema peripheral, generalized edema, swelling, localized
edema, face edema; dizziness includes dizziness, balance disorder; pruritus includes pruritus, pruritus genital; hemorrhage includes anal hemorrhage, hemothorax, gastrointestinal hemorrhage, hematochezia, hematuria, hemoptysis, hemorrhage intracranial, hyphema, small intestinal hemorrhage, upper gastrointestinal hemorrhage, vaginal hemorrhage; left ventricular dysfunction/cardiomyopathy includes ejection fraction decreased, cardiac failure, cardiac failure congestive.1,2 |
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Recommended dosage and administration1,2 | |
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Recommended dose: BRAFTOVI 450 mg (six 75-mg capsules) orally once daily + MEKTOVI 45 mg (three 15-mg tablets) orally twice daily, continued until disease progression or unacceptable toxicity |
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Instruct patients not to take a missed dose of: | |
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BRAFTOVI within 12 hours of the next dose |
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MEKTOVI within 6 hours of the next dose | |
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In case of vomiting, do not take an additional dose of BRAFTOVI + MEKTOVI; resume dosing with the next scheduled dose |
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For patients with moderate or severe hepatic impairment, the recommended dose of MEKTOVI is 30 mg orally taken twice daily |
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BRAFTOVI + MEKTOVI should be stored at room temperature |
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BRAFTOVI + MEKTOVI can be taken with or without food | |
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BRAF V600E is an actionable mutation in metastatic NSCLC1,2 | |
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NCCN Guidelines® recommend broad molecular profiling, including testing for BRAF V600E mutations, before initiating first-line therapy for patients with mNSCLC3 |
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Given that ~50% of patients with mNSCLC harbor a driver mutation, and ~2% of patients with mNSCLC have a BRAF V600E driver mutation, it is imperative to test all patients for BRAF V600E prior to initiating first-line therapy6-8 | |
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Making your patients’ support needs a priority. Together. | |
At Pfizer Oncology Together, we know how important it is that patients have access to their prescribed BRAFTOVI® (encorafenib) + MEKTOVI® (binimetinib) treatment. Pfizer Oncology Together is here to help you navigate the access and reimbursement process and help patients identify financial assistance options. For patients who need support for their day-to-day challenges, we can connect them to resources and organizations that may provide assistance. Because when it comes to patient support, we’re in this together. |
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ALT, alanine aminotransferase; AR, adverse reaction; AST, aspartate aminotransferase; BRAF, B-Raf proto-oncogene; BRAF-mt, BRAF-mutant; CI, confidence interval; CR, complete response; CTCAE, Common Terminology Criteria for Adverse Events; LV, left ventricular; MEK, mitogen-activated extracellular signal-regulated kinase; mNSCLC, metastatic non-small cell lung cancer; NCCN, National Comprehensive Cancer Network® (NCCN®); NSCLC, non-small cell lung cancer; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors.
BRAFTOVI® (encorafenib) and MEKTOVI® (binimetinib) are kinase inhibitors indicated for use in combination 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.
Limitations of Use: BRAFTOVI is not indicated for treatment of patients with wild-type BRAF NSCLC.
IMPORTANT SAFETY INFORMATION (cont'd)
The information below applies to the safety of the combination of BRAFTOVI and MEKTOVI unless otherwise noted. See full Prescribing Information for BRAFTOVI and for MEKTOVI for dose modifications for adverse reactions.
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.
Cardiomyopathy:
Cardiomyopathy manifesting as left ventricular dysfunction associated with symptomatic or asymptomatic decreases in ejection fraction, has been reported in patients. In the PHAROS trial, evidence of cardiomyopathy occurred in 11% and Grade 3 left ventricular dysfunction occurred in 1% of patients. Cardiomyopathy resolved in 82% of patients. Assess left ventricular ejection fraction (LVEF) by echocardiogram or multi-gated acquisition (MUGA) scan prior to initiating treatment, 1 month after initiating treatment, and then every 2 to 3 months during treatment. The safety has not been established in patients with a baseline ejection fraction that is either below 50% or below the institutional lower limit of normal (LLN). Patients with cardiovascular risk factors should be monitored
closely. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.
Hepatotoxicity:
Hepatotoxicity can occur when MEKTOVI is administered in combination with BRAFTOVI. In the PHAROS trial, the incidence of Grade 3 or 4 increases in liver function laboratory tests was 10% for aspartate aminotransferase (AST), 9% for alanine aminotransferase (ALT), and 3.2% for alkaline phosphatase. Monitor liver laboratory tests before initiation of BRAFTOVI and MEKTOVI, monthly during treatment, and as clinically indicated. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction. Rhabdomyolysis: Rhabdomyolysis can occur when MEKTOVI is administered in combination with BRAFTOVI. In the PHAROS trial, elevation of laboratory values of serum creatine kinase (CK) occurred in 41% of patients. No patient experienced rhabdomyolysis. Monitor CPK and
creatinine levels prior to initiating MEKTOVI, periodically during treatment, and as clinically indicated. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.
Rhabdomyolysis: Rhabdomyolysis can occur when MEKTOVI is administered in combination with BRAFTOVI. In the PHAROS trial, elevation of laboratory values of serum creatine kinase (CK) occurred in 41% of patients. No patient experienced rhabdomyolysis. Monitor CPK and creatinine levels prior to initiating MEKTOVI, periodically during treatment, and as clinically indicated. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.
Hemorrhage: Hemorrhage can occur when BRAFTOVI is administered in combination with MEKTOVI. In the PHAROS trial, hemorrhage occurred in 12% of patients, including fatal intracranial hemorrhage (1%); Grade 3 or 4 hemorrhage occurred in 4.1% of patients. The most frequent hemorrhagic events were anal hemorrhage and hemothorax (2% each). Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.
Venous Thromboembolism (VTE): In the PHAROS trial, VTE occurred in 7% of patients, including 1% of patients who developed pulmonary embolism. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.
Ocular Toxicities:
In the PHAROS trial, serous retinopathy (retinal detachment) occurred in 2% of patients with no cases of blindness. Retinal vein occlusion (RVO) is a known class-related adverse reaction of MEK inhibitors and may occur in patients treated with MEKTOVI in combination with BRAFTOVI. The safety of MEKTOVI has not been established in patients with a history of RVO or current risk factors for RVO including uncontrolled glaucoma or a history of hyperviscosity or hypercoagulability syndromes. Perform ophthalmological evaluation for patient-reported acute vision loss or other visual disturbance within 24 hours. Permanently discontinue MEKTOVI in patients with documented RVO. Uveitis, including iritis and iridocyclitis, was reported in patients treated with MEKTOVI in combination with
BRAFTOVI. In PHAROS, uveitis occurred in 1% of patients. 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. In the PHAROS trial, an increase in QTcF to >500 ms was measured in 2.1% (2/95) of patients who received BRAFTOVI with MEKTOVI. 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.
Interstitial Lung Disease (ILD): In the PHAROS trial, 1 patient (1%) receiving MEKTOVI with BRAFTOVI developed pneumonitis. Assess new or progressive unexplained pulmonary symptoms or findings for possible ILD. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.
Embryo-Fetal Toxicity: BRAFTOVI and MEKTOVI can cause fetal harm when administered to pregnant women. BRAFTOVI can render hormonal contraceptives ineffective. Effective, non-hormonal contraceptives should be used during treatment and for at least 30 days after the final dose for patients taking BRAFTOVI with MEKTOVI.
Risks Associated with BRAFTOVI as a Single Agent: There is an increased risk of certain adverse reactions compared to when BRAFTOVI is used in combination with MEKTOVI. If MEKTOVI is temporarily interrupted or permanently discontinued, reduce the dose of BRAFTOVI as recommended.
Risks Associated with Combination Treatment: BRAFTOVI is indicated for use as part of a regimen in combination with MEKTOVI. Refer to the prescribing information for BRAFTOVI and MEKTOVI for additional risk information.
Lactation: Advise women not to breastfeed during treatment with BRAFTOVI and MEKTOVI and for 2 weeks after the final dose.
Infertility: Advise males of reproductive potential that BRAFTOVI may impair fertility.
The most common adverse reactions (≥25%, all grades, in the PHAROS trial) for BRAFTOVI with MEKTOVI 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%).
Serious adverse reactions occurred in 38% of patients receiving BRAFTOVI with MEKTOVI. Serious adverse reactions (≥2% of patients in the PHAROS trial) were hemorrhage (6%), diarrhea (4.1%), anemia (3.1%), dyspnea (3.1%), pneumonia (3.1%), arrhythmia (2%), device related infection (2%), edema (2%), myocardial infarction (2%), and pleural effusion (2%). Fatal adverse reactions occurred in 2% of patients, including intracranial hemorrhage (1%) and myocardial infarction (1%).
Other clinically important adverse reactions occurring in <10% of patients who received BRAFTOVI with MEKTOVI in the PHAROS trial were peripheral neuropathy, dysgeusia, facial paresis, pancreatitis, hyperkeratosis, erythema, photosensitivity, and drug hypersensitivity.
In the PHAROS trial, the most common laboratory abnormalities (all grades) (≥20%) for BRAFTOVI and MEKTOVI included increased creatinine (91%), hyperglycemia (48%), anemia (47%), increased creatine kinase (41%), lipase increased (40%), increased ALT (34%), hypoalbuminemia (32%), increased alkaline phosphatase (31%), increased AST (31%), hyperkalemia (31%), hyponatremia (26%), lymphopenia (24%), serum amylase increased (22%), and thrombocytopenia (20%).
Strong or moderate CYP3A4 inhibitors: Avoid coadministration of BRAFTOVI with strong or moderate CYP3A4 inhibitors, including grapefruit juice. If coadministration is unavoidable, reduce the BRAFTOVI dose.
Strong CYP3A4 inducers: Avoid coadministration of BRAFTOVI with strong CYP3A4 inducers.
Sensitive CYP3A4 substrates: Avoid the coadministration of BRAFTOVI with CYP3A4 substrates (including hormonal contraceptives) for which a decrease in plasma concentration may lead to reduced efficacy of the substrate. If the coadministration cannot be avoided, see the CYP3A4 substrate product labeling for recommendations.
Dose reductions of drugs that are substrates of OATP1B1, OATP1B3, or BCRP may be required when used concomitantly with BRAFTOVI.
Avoid coadministration of BRAFTOVI with drugs known to prolong QT/QTc interval. |
References: 1. BRAFTOVI® (encorafenib) Prescribing Information. Array BioPharma, Inc.; March 2025. 2. MEKTOVI® (binimetinib) Prescribing Information. Array BioPharma, Inc.; March 2025. 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®
) for Non-Small Cell Lung Cancer V.1.2026. © National Comprehensive Cancer Network, Inc. 2025. All rights reserved. Accessed November 6, 2025. To view the most recent and complete version of the guidelines, 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. 4. Riely GJ, Smit EF, Ahn M-J, 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. 5. Data on file. Pfizer Inc. 6.
Alamgeer M, Ganju V, Watkins DN. Novel therapeutic targets in non-small cell lung cancer. Curr Opin Pharmacol. 2013;13(3):394-401. 7. Sathiyapalan A, Ellis PM. Molecular testing in non–small-cell lung cancer: a call to action. JCO Oncol Pract. 2024;20(1):7-9. 8. Roviello G, D'Angelo A, Sirico M, et al. Advances in anti-BRAF therapies for lung cancer. Invest New Drugs. 2021;39(3):879-890. |
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