Bevacizumab-BVZR

The BRAFTOVI combination regimen is the only approved targeted regimen for first-line BRAF-V600E mutant metastatic colorectal cancer Pivotal results from the Phase 3 portion with mFOLFOX6 of the BREAKWATER trial demonstrated a clinically meaningful and statistically significant 51% risk reduction in death and a 47% risk reduction in disease progression or death compared to chemotherapy treatment with or without bevacizumab Expanded indication enables flexibility to use BRAFTOVI in combination with cetuximab and different fluorouracil-based chemotherapy regimens NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) today announced that the U.S. Food and Drug Administration (FDA) has granted full approval to BRAFTOVI® (encorafenib) in combination with cetuximab (marketed as ERBITUX®) and fluorouracil-based chemotherapy for the treatment of adult patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation based on results from the global Phase 3 BREAKWATER trial (NCT04607421). BRAFTOVI in combination with cetuximab and mFOLFOX6 was granted accelerated approval by the FDA in December 2024 based on objective response rate (ORR) results, one of the BREAKWATER trial’s dual primary endpoints. The conversion from accelerated approval to full approval is based on significant benefit in outcomes for both progression-free survival (PFS), the trial’s other primary endpoint, and overall survival (OS), a key secondary endpoint, from the Phase 3 portion of the study that evaluated BRAFTOVIin combination with cetuximab and mFOLFOX6, as well as the ORR results from the Cohort 3 portion of the study, which evaluated BRAFTOVIin combination with cetuximab and FOLFIRI. “This landmark approval, achieved through the robust clinical benefit demonstrated in the BREAKWATER trial, validates that this targeted therapy can impact outcomes for people living with an aggressive, hard-to-treat cancer,” said Aamir Malik, Executive Vice President, Chief U.S. Commercial Officer, Pfizer. “As the only targeted combination regimen shown to deliver a significant improvement in certain outcomes for patients with BRAF V600E‑mutant metastatic colorectal cancer, BRAFTOVI is uniquely positioned to redefine first‑line treatment and establish a new standard of care. This approval reinforces our leadership in bringing differentiated, potentially practice‑changing cancer therapies to patients and healthcare providers who urgently need improved options.” “This approval gives oncologists confidence to use encorafenib plus cetuximab in combination with fluorouracil-based chemotherapy as a first-line standard of care for patients with BRAF V600E-mutant metastatic colorectal cancer,” said Scott Kopetz, M.D., Ph.D., FACP, Professor and Deputy Chair of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center and co-principal investigator of the BREAKWATER trial. “The BREAKWATER study demonstrated that these targeted combination regimens provided statistically significant benefit, providing the robust evidence we need to make treatment decisions that can meaningfully impact patient outcomes.” In the BREAKWATER study, the safety profile of both combination regimens continued to be consistent with the known safety profile of each respective agent in the regimen. No new safety signals were identified. The most common side effects (≥25%) in the mFOLFOX6 regimen were peripheral neuropathy, nausea, fatigue, diarrhea, decreased appetite, rash, vomiting, hemorrhage, abdominal pain, arthralgia, pyrexia, and constipation. The most common side effects (≥25%) in the FOLFIRI regimen were nausea, diarrhea, fatigue, vomiting, alopecia, constipation, abdominal pain, decreased appetite, and rash. Among patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6, 14% experienced an adverse reaction that resulted in permanent discontinuation of BRAFTOVI. There was no substantial difference in chemotherapy discontinuation due to side effects in the BRAFTOVI in combination with cetuximab and mFOLFOX6 arm compared with the chemotherapy, with or without bevacizumab arm. Among patients receiving BRAFTOVI in combination with cetuximab and FOLFIRI, 9% experienced an adverse reaction that resulted in permanent discontinuation of BRAFTOVI. The BRAFTOVI combination regimen with mFOLFOX6 is also under regulatory review in Europe, where Pierre Fabre Laboratories has exclusive commercialization rights, and was recently approved for use in several other countries. About BREAKWATER BREAKWATER is a Phase 3, randomized, active-controlled, open-label, multicenter trial of BRAFTOVI with cetuximab, alone or in combination with mFOLFOX6 or FOLFIRI (both fluorouracil-based chemotherapies) in participants with previously untreated BRAF V600E-mutant mCRC. Phase 3 Analysis: BRAFTOVI in combination with cetuximab and mFOLFOX6: Patients were randomized to receive BRAFTOVI 300 mg orally once daily in combination with cetuximab (discontinued after randomization of 158 patients), BRAFTOVI 300 mg orally once daily in combination with cetuximab and mFOLFOX6 (n=236) or mFOLFOX6, FOLFOXIRI, or CAPOX, with or without bevacizumab (control arm) (n=243). The dual primary endpoints for these study groups are ORR and PFS as assessed by BICR. OS is a key secondary endpoint. At the time of the PFS primary analysis, BRAFTOVI in combination with cetuximab and mFOLFOX6 significantly reduced the risk of disease progression or death by 47% compared to chemotherapy with or without bevacizumab (hazard ratio [HR] 0.53; 95% confidence interval [CI], 0.41, 0.68; p<0.0001) as assessed by blinded independent central review (BICR). Median PFS was 12.8 months (95% CI, 11.2, 15.9) with the BRAFTOVI combination regimen compared to 7.1 months (95% CI, 6.8, 8.5) with chemotherapy with or without bevacizumab. In a second interim analysis of median OS, BRAFTOVI plus cetuximab and mFOLFOX6 significantly reduced the risk of death by 51% compared to chemotherapy, with or without bevacizumab (HR 0.49; 95% CI, 0.38, 0.63; p<0.0001). Median OS doubled from 15.1 months with chemotherapy, with or without bevacizumab (95% CI, 13.7, 17.7) to 30.3 months (95% CI, 21.7, Not Estimated) with the BRAFTOVI combination regimen. These data were presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in the New England Journal of Medicine. Cohort 3 Analysis: BRAFTOVI in combination with cetuximab and FOLFIRI: In Cohort 3, patients were randomized to receive BRAFTOVI 300 mg orally once daily in combination with cetuximab and FOLFIRI (n=73) or FOLFIRI, with or without bevacizumab (control arm) (n=74). The primary endpoint of Cohort 3 is ORR as assessed by BICR. PFS is a key secondary endpoint; OS is a secondary endpoint summarized descriptively. BRAFTOVI plus cetuximab and FOLFIRI demonstrated a clinically meaningful and statistically significant improvement in confirmed ORR assessed by BICR compared to patients receiving FOLFIRI with or without bevacizumab (64% vs 39%, odds ratio =2.76, p=0.0011). These data were presented at the 2026 American Society of Clinical Oncology Gastrointestinal (ASCO GI®) Cancers Symposium. Detailed PFS results from Cohort 3 will be submitted for presentation at an upcoming medical meeting. About Colorectal Cancer (CRC) CRC is the third most common type of cancer in the world, with approximately 1.8 million new diagnoses in 2022.1 It is the second leading cause of cancer-related deaths.2 Overall, the lifetime risk of developing CRC is about 1 in 24 for men and 1 in 26 for women.2 In the U.S. alone, an estimated 158,850 people will be diagnosed with cancer of the colon or rectum in 2026, and approximately 55,000 are estimated to die from the disease each year.3 For 20% of those diagnosed with CRC, the disease has metastasized, or spread, making it harder to treat, and up to 50% of patients with localized disease eventually develop metastases.4 BRAF mutations are estimated to occur in 8-12% of people with mCRC and are associated with a poor prognosis for these patients.5 The BRAF V600E mutation is the most common BRAF mutation, and the risk of mortality in CRC patients with the BRAF V600E mutation is more than double that of patients with no known mutation present.5-7 Despite the high unmet need in BRAF V600E-mutant mCRC, prior to the BRAFTOVI accelerated FDA approval in this indication on December 20, 2024, there were no approved biomarker-driven therapies specifically indicated for people with previously untreated BRAF V600E-mutant mCRC.8,9 About BRAFTOVI® (encorafenib) BRAFTOVI is an oral small molecule kinase inhibitor that targets BRAF V600E. Inappropriate activation of proteins in the MAPK signaling pathway (RAS-RAF-MEK-ERK) has been shown to occur in certain cancers, including CRC. Pfizer has exclusive rights to BRAFTOVI in the U.S., Canada, Latin America, Middle East, and Africa. Ono Pharmaceutical Co., Ltd. has exclusive rights to commercialize the product in Japan and South Korea, Medison has exclusive rights to commercialize the product in Israel and Pierre Fabre Laboratories has exclusive rights to commercialize the product in all other countries, including Europe and Asia (excluding Japan and South Korea). INDICATION AND USAGE BRAFTOVI® (encorafenib) is indicated, in combination with cetuximab and fluorouracil-based chemotherapy, for the treatment of adult patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, as detected by an FDA-authorized test. Limitations of Use: BRAFTOVI is not indicated for treatment of patients with wild-type BRAF CRC. IMPORTANT SAFETY INFORMATION Refer to the prescribing information for cetuximab and individual product components of mFOLFOX6 and FOLFIRI for recommended dosing and additional safety information. WARNINGS AND PRECAUTIONS New Primary Malignancies: New primary malignancies, cutaneous and noncutaneous, can occur. In the BREAKWATER trial, the following cutaneous malignancies occurred in patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6: melanocytic nevus in 5.6%, skin papilloma in 3%, basal cell carcinoma in 1.3%, squamous cell carcinoma of skin in 0.9%, keratoacanthoma in 0.4% and malignant melanoma in situ in 0.4%. In patients who received BRAFTOVI in combination with cetuximab and FOLFIRI, skin papilloma occurred in 2.8% and keratoacanthoma in 1.4% 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 noncutaneous malignancies. Discontinue BRAFTOVI for RAS mutation-positive noncutaneous malignancies. Monitor patients for new malignancies prior to initiation of treatment, while on treatment, and after discontinuation of treatment. 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-authorized 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. Assess left ventricular ejection fraction (LVEF) by echocardiogram or multigated 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. In the BREAKWATER trial, the incidence of Grade 3 or 4 increases in liver function laboratory tests in patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6 was 2.6% for alkaline phosphatase, 1.3% each for ALT and AST. In patients receiving BRAFTOVI in combination with cetuximab and FOLFIRI, the incidence of Grade 3 or 4 increases in liver function laboratory tests was 1.5% each for ALT and AST. Monitor liver laboratory tests before initiation of BRAFTOVI, monthly during treatment, and as clinically indicated. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction. Hemorrhage: Hemorrhage can occur. In the BREAKWATER trial, hemorrhage occurred in 34% of patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6; Grade 3 or 4 hemorrhage occurred in 3% of patients. In patients receiving BRAFTOVI in combination with cetuximab and FOLFIRI, hemorrhage occurred in 21% of patients. 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. In BREAKWATER, the incidence of uveitis among patients who received BRAFTOVI in combination with cetuximab and mFOLFOX6 was 0.4%. 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 BREAKWATER trial, an increase of QTcF >500 ms was measured in 4% (9/226) of patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6. In patients receiving BRAFTOVI in combination with cetuximab and FOLFIRI, an increase of QTcF >500 ms was measured in 1.5% (1/65) of 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 pregnant women. BRAFTOVI can render hormonal contraceptives ineffective. Advise females of reproductive potential to use effective nonhormonal contraception during treatment with BRAFTOVI and for 2 weeks after the final dose. Risks Associated with Combination Treatment: BRAFTOVI is indicated for use as part of a regimen in combination with cetuximab and mFOLFOX6 or FOLFIRI. Refer to the prescribing information for cetuximab and individual product components of mFOLFOX6 and FOLFIRI for additional risk information. 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. ADVERSE REACTIONS BRAF V600Emutation-positive mCRC, in combination with cetuximab and mFOLFOX6 Serious adverse reactions occurred in 46% of patients who received BRAFTOVI in combination with cetuximab and mFOLFOX6. Serious adverse reactions in >3% of patients included intestinal obstruction (4.7%), pyrexia (3.9%), sepsis (3.4%), and abdominal pain (3.4%) Fatal intestinal obstruction occurred in 0.9%, and fatal large intestinal perforation andgastrointestinal perforation occurred in 0.4% (each) in patients who received BRAFTOVI in combination with cetuximab and mFOLFOX6 Most common adverse reactions (≥25%, all grades) in the BRAFTOVI with cetuximab and mFOLFOX6 arm compared to the control arm (mFOLFOX6 ± bevacizumab or FOLFOXIRI ± bevacizumab or CAPOX ± bevacizumab), and a subset of the control arm (mFOLFOX6 ± bevacizumab), respectively were: peripheral neuropathy (64% vs 53% and 57%), nausea (54% vs 50% and 44%), fatigue (53% vs 41% and 45%), diarrhea (42% vs 50% and 44%), decreased appetite (38% vs 27% and 30%), rash (36% vs 6% and 5%), vomiting (36% vs 22% and 17%), hemorrhage (34% vs 21% and 15%), abdominal pain (32% vs 31% and 30%), arthralgia (32% vs 6% and 7%), pyrexia (29% vs 16% and 17%), and constipation (27% vs 23% and 25%) Most common laboratory abnormalities(≥10%, grade 3 or 4) in the BRAFTOVI with cetuximab and mFOLFOX6 arm compared to the control arm (mFOLFOX6 ± bevacizumab or FOLFOXIRI ± bevacizumab or CAPOX ± bevacizumab), and a subset of the control arm (mFOLFOX6 ± bevacizumab), respectively were: increased lipase (53% vs 28% and 23%), decreased neutrophil count (37% vs 35% and 33%), decreased hemoglobin (19% vs 6% and 7%), decreased white blood cell count (12% vs 8% and 6%), and increased glucose (11% vs 2% and 1%) BRAF V600E mutation-positive mCRC, in combination with cetuximab and FOLFIRI Serious adverse reactions occurred in 39% of patients who received BRAFTOVI in combination with cetuximab and FOLFIRI. Serious adverse reactions in >3% of patients included febrile neutropenia (5.6%) and infusion related reaction (4.2%) Fatal gastrointestinal perforation occurred in 1.4% of patients who received BRAFTOVI in combination with cetuximab and FOLFIRI Most common adverse reactions (>25%, all grades) in the BRAFTOVI with cetuximab and FOLFIRI arm compared to the control arm (FOLFIRI ± bevacizumab) were nausea (61% vs 57%), diarrhea (55% vs 49%), fatigue (47% vs 50%), vomiting (47% vs 31%), alopecia (35% vs 22%), constipation (31% vs 29%), abdominal pain (30% vs 22%), decreased appetite (30% vs 32%), and rash (27% vs 1.5%) Most common laboratory abnormalities (≥10%, grade 3 or 4) in the BRAFTOVI with cetuximab and FOLFIRI arm compared to the control arm (FOLFIRI ± bevacizumab) were: decreased neutrophil count (30% vs 32%), increased lipase (22% vs 12%), decreased white blood cell count (20% vs 6%), and decreased hemoglobin (10% vs 3%) DRUG INTERACTIONS 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. View the full Prescribing Information. There may be a delay as the document is updated with the latest information. It will be available as soon as possible. Please check back for the updated full information shortly. About Pfizer Oncology At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and multispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, gastrointestinal cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives. About Pfizer: Breakthroughs That Change Patients’ Lives At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on X at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer. Disclosure Notice The information contained in this release is as of February 24, 2026. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. This release contains forward-looking information about BRAFTOVI® (encorafenib) and an approval in the U.S. for BRAFTOVI in combination with cetuximab and fluorouracil-based chemotherapy for the treatment of adult patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, including their potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, uncertainties regarding the commercial success of BRAFTOVI plus cetuximab and fluorouracil-based chemotherapy; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when any drug applications may be filed in any additional jurisdictions for BRAFTOVI plus cetuximab and fluorouracil-based chemotherapy for the treatment of adult patients with metastatic CRC with a BRAF V600E mutation or in any jurisdictions for any other potential indications for BRAFTOVI; whether and when any such other applications may be approved by other regulatory authorities, which will depend on myriad factors, including making a determination as to whether the product's benefits outweigh its known risks and determination of the product's efficacy and, if approved, whether BRAFTOVI plus cetuximab and fluorouracil-based chemotherapy will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of BRAFTOVI or BRAFTOVI plus cetuximab and fluorouracil-based chemotherapy; risks and uncertainties related to issued or future executive orders or other new, or changes in, laws or regulations; uncertainties regarding the impact of COVID-19 on Pfizer’s business, operations and financial results; and competitive developments. A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2024 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com. ERBITUX® is a registered trademark of Eli Lilly and Company its subsidiaries, or affiliates. References Media Contact: PfizerMediaRelations@Pfizer.com Investor Contact: IR@Pfizer.com Source: Pfizer Inc.

The BRAFTOVI combination regimen is the only approved targeted regimen for first-line BRAFTOVI联合治疗方案是唯一获批的一线靶向治疗方案。BRAF-V600E BRAF-V600Emutant metastatic colorectal cancer 转移性结直肠癌突变体Pivotal results from the Phase 3 portion with mFOLFOX6 of the BREAKWATER trial demonstrated a clinically meaningful and statistically significant 51% risk reduction in death and a 47% risk reduction in disease progression or death compared to chemotherapy treatment with or without bevacizumab 关键的第三阶段mFOLFOX6部分的BREAKWATER试验结果表明，与使用或不使用贝伐单抗的化疗相比，死亡风险显著降低了51%，疾病进展或死亡的风险降低了47%，具有临床意义和统计学显著性。Expanded indication enables flexibility to use BRAFTOVI in combination with cetuximab and different fluorouracil-based chemotherapy regimens 扩大的适应症使得可以灵活地将BRAFTOVI与西妥昔单抗和不同的氟尿嘧啶类化疗方案联合使用。 NEW YORK--(BUSINESS WIRE)-- 纽约--（商业资讯）--Pfizer Inc 辉瑞公司. (NYSE: PFE) today announced that the U.S. Food and Drug Administration (FDA) has granted full approval to BRAFTOVI .（纽约证券交易所代码：PFE）今天宣布，美国食品和药物管理局 (FDA) 已完全批准 BRAFTOVI。® ®(encorafenib) in combination with cetuximab (marketed as ERBITUX (encorafenib) 与西妥昔单抗（商品名：ERBITUX）联合使用® ®) and fluorouracil-based chemotherapy for the treatment of adult patients with metastatic colorectal cancer (mCRC) with a ）和基于氟尿嘧啶的化疗，用于治疗患有转移性结直肠癌（mCRC）的成年患者，具有BRAF V600E BRAF V600E突变mutation based on results from the global Phase 3 BREAKWATER trial ( 基于全球三期BREAKWATER试验结果的突变 (NCT04607421 NCT04607421). ）。BRAFTOVI in combination with cetuximab and mFOLFOX6 was granted accelerated approval by the FDA in December 2024 based on objective response rate (ORR) results, one of the BREAKWATER trial’s dual primary endpoints. The conversion from accelerated approval to full approval is based on significant benefit in outcomes for both progression-free survival (PFS), the trial’s other primary endpoint, and overall survival (OS), a key secondary endpoint, from the Phase 3 portion of the study that evaluated BRAFTOVI. 2024年12月，基于客观缓解率（ORR）结果，BRAFTOVI联合西妥昔单抗和mFOLFOX6获得了FDA的加速批准，这是BREAKWATER试验的双重主要终点之一。从加速批准转为完全批准是基于该研究的3期部分评估BRAFTOVI时，在另一个主要终点无进展生存期（PFS）以及关键次要终点总生存期（OS）方面取得的显著益处。in combination with cetuximab and mFOLFOX6, as well as the ORR results from the Cohort 3 portion of the study, which evaluated BRAFTOVI 与西妥昔单抗和mFOLFOX6联合使用，以及研究中队列3部分评估BRAFTOVI的ORR结果，in combination with cetuximab and FOLFIRI. 与西妥昔单抗和FOLFIRI联合使用。“This landmark approval, achieved through the robust clinical benefit demonstrated in the BREAKWATER trial, validates that this targeted therapy can impact outcomes for people living with an aggressive, hard-to-treat cancer,” said Aamir Malik, Executive Vice President, Chief U.S. Commercial Officer, Pfizer. “这项具有里程碑意义的批准是通过BREAKWATER试验中展示的强大临床效益实现的，验证了这种靶向疗法可以对患有侵袭性、难治性癌症的患者产生影响，”辉瑞执行副总裁、美国首席商务官Aamir Malik表示。“As the only targeted combination regimen shown to deliver a significant improvement in certain outcomes for patients with. “作为唯一被证实可为某些患者带来特定疗效显著改善的靶向联合治疗方案。BRAF V600E BRAF V600E突变‑mutant metastatic colorectal cancer, BRAFTOVI is uniquely positioned to redefine first‑line treatment and establish a new standard of care. This approval reinforces our leadership in bringing differentiated, potentially practice‑changing cancer therapies to patients and healthcare providers who urgently need improved options.”. ‑突变型转移性结直肠癌，BRAFTOVI 独具优势，有望重新定义一线治疗并确立新的护理标准。此次批准进一步巩固了我们在为急需改进治疗方案的患者和医疗保健提供者带来差异化、可能改变临床实践的癌症疗法方面的领导地位。“This approval gives oncologists confidence to use encorafenib plus cetuximab in combination with fluorouracil-based chemotherapy as a first-line standard of care for patients with “这一批准使肿瘤学家有信心将恩科拉非尼联合西妥昔单抗以及基于氟尿嘧啶的化疗作为一线治疗标准，用于BRAF V600E BRAF V600E突变-mutant metastatic colorectal cancer,” said Scott Kopetz, M.D., Ph.D., FACP, Professor and Deputy Chair of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center and co-principal investigator of the BREAKWATER trial. “The BREAKWATER study demonstrated that these targeted combination regimens provided statistically significant benefit, providing the robust evidence we need to make treatment decisions that can meaningfully impact patient outcomes.”. “突变型转移性结直肠癌，”德克萨斯大学MD安德森癌症中心胃肠道肿瘤内科教授兼副主任、BREAKWATER试验的联合首席研究员Scott Kopetz医学博士、哲学博士、FACP表示。“BREAKWATER研究证明，这些靶向组合方案具有统计学上的显著益处，为我们提供了有力的证据，以制定能够对患者预后产生有意义影响的治疗决策。”In the BREAKWATER study, the safety profile of both combination regimens continued to be consistent with the known safety profile of each respective agent in the regimen. No new safety signals were identified. The most common side effects (≥25%) in the mFOLFOX6 regimen were peripheral neuropathy, nausea, fatigue, diarrhea, decreased appetite, rash, vomiting, hemorrhage, abdominal pain, arthralgia, pyrexia, and constipation. 在 BREAKWATER 研究中，两种联合治疗方案的安全性表现仍然与方案中各药物已知的安全性特征一致。没有发现新的安全性信号。mFOLFOX6 方案中最常见的副作用（≥25%）包括外周神经病变、恶心、疲劳、腹泻、食欲减退、皮疹、呕吐、出血、腹痛、关节痛、发热和便秘。The most common side effects (≥25%) in the FOLFIRI regimen were nausea, diarrhea, fatigue, vomiting, alopecia, constipation, abdominal pain, decreased appetite, and rash.. FOLFIRI方案中最常见的副作用（≥25%）包括恶心、腹泻、疲劳、呕吐、脱发、便秘、腹痛、食欲减退和皮疹。Among patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6, 14% experienced an adverse reaction that resulted in permanent discontinuation of BRAFTOVI. There was no substantial difference in chemotherapy discontinuation due to side effects in the BRAFTOVI in combination with cetuximab and mFOLFOX6 arm compared with the chemotherapy, with or without bevacizumab arm. 在联合使用BRAFTOVI、西妥昔单抗和mFOLFOX6的患者中，有14%的患者出现了导致永久停用BRAFTOVI的不良反应。与化疗（无论是否联合贝伐单抗）组相比，BRAFTOVI联合西妥昔单抗和mFOLFOX6组因副作用导致化疗停用的比例没有显著差异。Among patients receiving BRAFTOVI in combination with cetuximab and FOLFIRI, 9% experienced an adverse reaction that resulted in permanent discontinuation of BRAFTOVI.. 在联合使用BRAFTOVI、西妥昔单抗和FOLFIRI的患者中，9%的患者出现了导致永久停用BRAFTOVI的不良反应。The BRAFTOVI combination regimen with mFOLFOX6 is also under regulatory review in Europe, where Pierre Fabre Laboratories has exclusive commercialization rights, and was recently approved for use in several other countries. BRAFTOVI联合mFOLFOX6的治疗方案也正在欧洲接受监管审查，皮尔法伯实验室在欧洲拥有独家商业化权利，并且最近已获准在其他几个国家使用。About BREAKWATER 关于防波堤BREAKWATER is a Phase 3, randomized, active-controlled, open-label, multicenter trial of BRAFTOVI with cetuximab, alone or in combination with mFOLFOX6 or FOLFIRI (both fluorouracil-based chemotherapies) in participants with previously untreated BREAKWATER是一项III期、随机、活性对照、开放标签、多中心试验，研究BRAFTOVI联合西妥昔单抗，单独使用或与mFOLFOX6或FOLFIRI（均为基于氟尿嘧啶的化疗方案）联合用于既往未经治疗的参与者。 BRAF V600E BRAF V600E突变 -mutant mCRC. -突变型mCRC。Phase 3 Analysis: BRAFTOVI in combination with cetuximab and mFOLFOX6: 第三阶段分析：BRAFTOVI联合西妥昔单抗和mFOLFOX6：Patients were randomized to receive BRAFTOVI 300 mg orally once daily in combination with cetuximab (discontinued after randomization of 158 patients), BRAFTOVI 300 mg orally once daily in combination with cetuximab and mFOLFOX6 (n=236) or mFOLFOX6, FOLFOXIRI, or CAPOX, with or without bevacizumab (control arm) (n=243). 患者被随机分配接受每日一次口服BRAFTOVI 300 mg联合西妥昔单抗（在158名患者随机分组后停用），每日一次口服BRAFTOVI 300 mg联合西妥昔单抗和mFOLFOX6（n=236），或mFOLFOX6、FOLFOXIRI或CAPOX，伴或不伴贝伐珠单抗（对照组）（n=243）。The dual primary endpoints for these study groups are ORR and PFS as assessed by BICR. OS is a key secondary endpoint.. 这些研究组的双重主要终点是ORR和BICR评估的PFS。OS是一个关键的次要终点。At the time of the PFS primary analysis, BRAFTOVI in combination with cetuximab and mFOLFOX6 significantly reduced the risk of disease progression or death by 47% compared to chemotherapy with or without bevacizumab (hazard ratio [HR] 0.53; 95% confidence interval [CI], 0.41, 0.68; p<0.0001) as assessed by blinded independent central review (BICR). 在PFS主要分析时，根据盲态独立中心审查（BICR）评估，与化疗联合或不联合贝伐珠单抗相比，BRAFTOVI联合西妥昔单抗和mFOLFOX6显著降低了47%的疾病进展或死亡风险（风险比[HR] 0.53；95%置信区间[CI]，0.41, 0.68；p<0.0001）。Median PFS was 12.8 months (95% CI, 11.2, 15.9) with the BRAFTOVI combination regimen compared to 7.1 months (95% CI, 6.8, 8.5) with chemotherapy with or without bevacizumab. In a second interim analysis of median OS, BRAFTOVI plus cetuximab and mFOLFOX6 significantly reduced the risk of death by 51% compared to chemotherapy, with or without bevacizumab (HR 0.49; 95% CI, 0.38, 0.63; p<0.0001). BRAFTOVI联合治疗方案的中位无进展生存期（PFS）为12.8个月（95% CI，11.2, 15.9），而化疗联合或不联合贝伐单抗的中位无进展生存期为7.1个月（95% CI，6.8, 8.5）。在第二次中期分析中，BRAFTOVI联合西妥昔单抗和mFOLFOX6相较于化疗（无论是否联合贝伐单抗）显著降低了51%的死亡风险（HR 0.49；95% CI，0.38, 0.63；p<0.0001）。 Median OS doubled from 15.1 months with chemotherapy, with or without bevacizumab (95% CI, 13.7, 17.7) to 30.3 months (95% CI, 21.7, Not Estimated) with the BRAFTOVI combination regimen. These data were . 中位总生存期（OS）从使用化疗（无论是否联合贝伐单抗）的15.1个月（95%置信区间：13.7，17.7）翻倍至使用BRAFTOVI联合治疗方案的30.3个月（95%置信区间：21.7，未估计）。这些数据为。presented 呈现at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in the 在2025年美国临床肿瘤学会（ASCO）年会上同时发表在New England Journal of Medicine 新英格兰医学杂志. 。Cohort 3 Analysis: BRAFTOVI in combination with cetuximab and FOLFIRI: 队列3分析：BRAFTOVI联合西妥昔单抗和FOLFIRI：In Cohort 3, patients were randomized to receive BRAFTOVI 300 mg orally once daily in combination with cetuximab and FOLFIRI (n=73) or FOLFIRI, with or without bevacizumab (control arm) (n=74). The primary endpoint of Cohort 3 is ORR as assessed by BICR. PFS is a key secondary endpoint; OS is a secondary endpoint summarized descriptively.. 在队列3中，患者被随机分配接受每日一次口服BRAFTOVI 300 mg联合西妥昔单抗和FOLFIRI（n=73），或FOLFIRI，伴或不伴贝伐珠单抗（对照组）（n=74）。队列3的主要终点是由BICR评估的ORR。PFS是一个关键的次要终点；OS是一个描述性总结的次要终点。BRAFTOVI plus cetuximab and FOLFIRI demonstrated a clinically meaningful and statistically significant improvement in confirmed ORR assessed by BICR compared to patients receiving FOLFIRI with or without bevacizumab (64% vs 39%, odds ratio =2.76, p=0.0011). These data were presented at the BRAFTOVI联合西妥昔单抗和FOLFIRI方案相比接受FOLFIRI联合或不联合贝伐珠单抗的患者，经BICR评估确认的客观缓解率（ORR）显示出具有临床意义且统计学显著的改善（64% vs 39%，优势比=2.76，p=0.0011）。这些数据在会议上展示。2026 American Society of Clinical Oncology Gastrointestinal (ASCO GI®) Cancers Symposium 2026年美国临床肿瘤学会胃肠道（ASCO GI®）癌症研讨会. Detailed PFS results from Cohort 3 will be submitted for presentation at an upcoming medical meeting. . 第三组的详细PFS结果将提交在即将召开的医学会议上进行展示。About Colorectal Cancer (CRC) 关于结直肠癌（CRC） CRC is the third most common type of cancer in the world, with approximately 1.8 million new diagnoses in 2022. CRC是世界上第三大常见癌症类型，2022年大约有180万新诊断病例。1 1It is the second leading cause of cancer-related deaths. 它是癌症相关死亡的第二大原因。2 2Overall, the lifetime risk of developing CRC is about 1 in 24 for men and 1 in 26 for women. 总体而言，男性患结直肠癌的终生风险约为1/24，女性为1/26。2 2In the U.S. alone, an estimated 158,850 people will be diagnosed with cancer of the colon or rectum in 2026, and approximately 55,000 are estimated to die from the disease each year. 仅在美国，预计到 2026 年将有约 158,850 人被诊断出患有结肠癌或直肠癌，每年估计有 55,000 人死于该疾病。3 3For 20% of those diagnosed with CRC, the disease has metastasized, or spread, making it harder to treat, and up to 50% of patients with localized disease eventually develop metastases. 在被诊断为结直肠癌的患者中，有20%的人病情已经发生转移或扩散，导致更难治疗，而高达50%的局部病灶患者最终会发展为转移。4 4BRAF BRAFmutations are estimated to occur in 8-12% of people with mCRC and are associated with a poor prognosis for these patients. 据估计，8-12%的mCRC患者会发生突变，这些患者的预后较差。5 5The TheBRAF V600E BRAF V600E突变 mutation is the most common 变异是最常见的BRAF BRAFmutation, and the risk of mortality in CRC patients with the 突变，以及携带该突变的CRC患者的死亡风险 BRAF V600E BRAF V600E突变mutation is more than double that of patients with no known mutation present. 比未发现已知突变的患者的突变率高出一倍多。5-7 5-7Despite the high unmet need in 尽管存在高度未满足的需求BRAF V600E BRAF V600E突变-mutant mCRC, prior to the BRAFTOVI accelerated FDA approval in this indication on December 20, 2024, there were no approved biomarker-driven therapies specifically indicated for people with previously untreated -突变型mCRC，在2024年12月20日BRAFTOVI在此适应症上获得FDA加速批准之前，尚无获批的专门针对未经治疗的患者的生物标志物驱动疗法。BRAF V600E BRAF V600E突变-mutant mCRC. -突变型mCRC。8,9 8,9About BRAFTOVI 关于BRAFTOVI® ®(encorafenib) （恩考芬尼）BRAFTOVI is an oral small molecule kinase inhibitor that targets BRAFTOVI 是一种口服小分子激酶抑制剂，靶向BRAF V600E BRAF V600E突变. Inappropriate activation of proteins in the MAPK signaling pathway (RAS-RAF-MEK-ERK) has been shown to occur in certain cancers, including CRC. 在某些癌症（包括结直肠癌）中，已证明MAPK信号通路（RAS-RAF-MEK-ERK）中的蛋白质不适当激活会发生。Pfizer has exclusive rights to BRAFTOVI in the U.S., Canada, Latin America, Middle East, and Africa. Ono Pharmaceutical Co., Ltd. has exclusive rights to commercialize the product in Japan and South Korea, Medison has exclusive rights to commercialize the product in Israel and Pierre Fabre Laboratories has exclusive rights to commercialize the product in all other countries, including Europe and Asia (excluding Japan and South Korea).. 辉瑞在美国、加拿大、拉丁美洲、中东和非洲拥有BRAFTOVI的独家权利。小野制药株式会社在日本和韩国拥有该产品的独家商业化权利，Medison在以色列拥有该产品的独家商业化权利，皮埃尔·法布雷实验室在包括欧洲和亚洲（不包括日本和韩国）的所有其他国家拥有该产品的独家商业化权利。INDICATION AND USAGE 适应症和用法 BRAFTOVI BRAFTOVI® ®(encorafenib) is indicated, in combination with cetuximab and fluorouracil-based chemotherapy, for the treatment of adult patients with metastatic colorectal cancer (mCRC) with a (encorafenib)联合西妥昔单抗和基于氟尿嘧啶的化疗，适用于治疗患有转移性结直肠癌（mCRC）的成年患者，这些患者的特征是BRAF BRAFV600E mutation, as detected by an FDA-authorized test. 由FDA授权的检测方法检测到的V600E突变。Limitations of Use 使用限制: BRAFTOVI is not indicated for treatment of patients with wild-type ：BRAFTOVI不适用于治疗野生型患者BRAF BRAFCRC. 循环冗余校验。IMPORTANT SAFETY INFORMATION 重要安全信息 Refer to the prescribing information for cetuximab and individual product components of mFOLFOX6 and FOLFIRI for recommended dosing and additional safety information. 参考西妥昔单抗的处方信息以及mFOLFOX6和FOLFIRI的个别产品成分，获取推荐剂量和额外的安全信息。WARNINGS AND PRECAUTIONS 警告和注意事项New Primary Malignancies: 新发原发恶性肿瘤：New primary malignancies, cutaneous and noncutaneous, can occur. In the BREAKWATER trial, the following cutaneous malignancies occurred in patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6: melanocytic nevus in 5.6%, skin papilloma in 3%, basal cell carcinoma in 1.3%, squamous cell carcinoma of skin in 0.9%, keratoacanthoma in 0.4% and malignant melanoma in situ in 0.4%. 新的原发性恶性肿瘤，包括皮肤和非皮肤的，可能会发生。在BREAKWATER试验中，接受BRAFTOVI联合西妥昔单抗和mFOLFOX6治疗的患者中，发生了以下皮肤恶性肿瘤：黑色素细胞痣占5.6%，皮肤乳头状瘤占3%，基底细胞癌占1.3%，皮肤鳞状细胞癌占0.9%，角化棘皮瘤占0.4%，原位恶性黑色素瘤占0.4%。In patients who received BRAFTOVI in combination with cetuximab and FOLFIRI, skin papilloma occurred in 2.8% and keratoacanthoma in 1.4% of patients. Perform dermatologic evaluations prior to initiating treatment, every 2 months during treatment, and for up to 6 months following discontinuation of treatment. 在接受BRAFTOVI联合西妥昔单抗和FOLFIRI治疗的患者中，2.8%的患者出现了皮肤乳头状瘤，1.4%的患者出现了角化棘皮瘤。在开始治疗前、治疗期间每2个月以及停止治疗后长达6个月内，进行皮肤科评估。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 noncutaneous malignancies. 通过切除和皮肤病理学评估来管理可疑的皮肤病变。对于新的原发性皮肤恶性肿瘤，不建议调整剂量。基于其作用机制，BRAFTOVI可能通过RAS突变或其他机制激活促进相关恶性肿瘤的发生。监测接受BRAFTOVI治疗的患者，留意非皮肤恶性肿瘤的体征和症状。Discontinue BRAFTOVI for RAS mutation-positive noncutaneous malignancies. Monitor patients for new malignancies prior to initiation of treatment, while on treatment, and after discontinuation of treatment.. 对于RAS突变阳性的非皮肤恶性肿瘤，停止使用BRAFTOVI。在治疗开始前、治疗期间以及治疗结束后，监测患者是否出现新的恶性肿瘤。Tumor Promotion in 肿瘤促进在BRAF BRAFWild-Type Tumors: 野生型肿瘤：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 体外实验已证明，暴露于BRAF抑制剂中的BRAF野生型细胞会出现MAP激酶信号传导的反常激活及细胞增殖增加。确认证据BRAF BRAFV600E or V600K mutation using an FDA-authorized test prior to initiating BRAFTOVI. 在开始使用BRAFTOVI之前，使用FDA授权的测试检测V600E或V600K突变。Cardiomyopathy: 心肌病：Cardiomyopathy manifesting as left ventricular dysfunction associated with symptomatic or asymptomatic decreases in ejection fraction, has been reported in patients. Assess left ventricular ejection fraction (LVEF) by echocardiogram or multigated acquisition (MUGA) scan prior to initiating treatment, 1 month after initiating treatment, and then every 2 to 3 months during treatment. 心肌病表现为左心室功能障碍，伴有症状性或无症状性射血分数降低，已在患者中报告。在开始治疗前、开始治疗后1个月以及治疗期间每2至3个月，通过超声心动图或多门控采集（MUGA）扫描评估左心室射血分数（LVEF）。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.. 对于基线射血分数低于50%或低于正常范围（LLN）的患者，安全性尚未确定。具有心血管风险因素的患者应密切监测。根据不良反应的严重程度，暂停用药、减少剂量或永久停药。Hepatotoxicity: 肝毒性：Hepatotoxicity can occur. In the BREAKWATER trial, the incidence of Grade 3 or 4 increases in liver function laboratory tests in patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6 was 2.6% for alkaline phosphatase, 1.3% each for ALT and AST. In patients receiving BRAFTOVI in combination with cetuximab and FOLFIRI, the incidence of Grade 3 or 4 increases in liver function laboratory tests was 1.5% each for ALT and AST. 肝毒性可能会发生。在BREAKWATER试验中，接受BRAFTOVI联合西妥昔单抗和mFOLFOX6治疗的患者中，肝功能实验室检测指标升高至3级或4级的发生率为：碱性磷酸酶2.6%，ALT和AST各1.3%。在接受BRAFTOVI联合西妥昔单抗和FOLFIRI治疗的患者中，肝功能实验室检测指标升高至3级或4级的发生率为：ALT和AST各1.5%。Monitor liver laboratory tests before initiation of BRAFTOVI, monthly during treatment, and as clinically indicated. Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.. 在开始使用BRAFTOVI之前、治疗期间每月以及根据临床需要监测肝脏实验室测试。根据不良反应的严重程度，暂停、减少剂量或永久停用。Hemorrhage: 出血：Hemorrhage can occur. In the BREAKWATER trial, hemorrhage occurred in 34% of patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6; Grade 3 or 4 hemorrhage occurred in 3% of patients. In patients receiving BRAFTOVI in combination with cetuximab and FOLFIRI, hemorrhage occurred in 21% of patients. 出血可能发生。在BREAKWATER试验中，接受BRAFTOVI联合西妥昔单抗和mFOLFOX6治疗的患者中有34%发生出血；其中3%的患者出现3级或4级出血。在接受BRAFTOVI联合西妥昔单抗和FOLFIRI治疗的患者中，21%的患者发生出血。Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.. 根据不良反应的严重程度，暂停、减少剂量或永久停用。Uveitis: 葡萄膜炎：Uveitis, including iritis and iridocyclitis, has been reported in patients treated with BRAFTOVI. In BREAKWATER, the incidence of uveitis among patients who received BRAFTOVI in combination with cetuximab and mFOLFOX6 was 0.4%. 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. 据报道，接受BRAFTOVI治疗的患者出现了葡萄膜炎，包括虹膜炎和虹膜睫状体炎。在BREAKWATER研究中，接受BRAFTOVI联合西妥昔单抗和mFOLFOX6治疗的患者中，葡萄膜炎的发生率为0.4%。每次就诊时评估视觉症状。定期进行眼科评估，并对新发或恶化的视觉障碍以及新发或持续的眼科检查结果进行随访。Withhold, reduce dose, or permanently discontinue based on severity of adverse reaction.. 根据不良反应的严重程度，暂停、减少剂量或永久停用。QT Prolongation: QT间期延长：BRAFTOVI is associated with dose-dependent QTc interval prolongation in some patients. In the BREAKWATER trial, an increase of QTcF >500 ms was measured in 4% (9/226) of patients receiving BRAFTOVI in combination with cetuximab and mFOLFOX6. In patients receiving BRAFTOVI in combination with cetuximab and FOLFIRI, an increase of QTcF >500 ms was measured in 1.5% (1/65) of patients. BRAFTOVI 在部分患者中与剂量依赖性的 QTc 间期延长有关。在 BREAKWATER 试验中，接受 BRAFTOVI 联合西妥昔单抗和 mFOLFOX6 治疗的患者中，有 4%（9/226）的患者测量到 QTcF >500 毫秒的增加。在接受 BRAFTOVI 联合西妥昔单抗和 FOLFIRI 治疗的患者中，有 1.5%（1/65）的患者测量到 QTcF >500 毫秒的增加。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. 监测已经存在或有显著风险发展为QTc间期延长的患者，包括已知长QT综合征、临床显著的心动过缓心律失常、严重或未控制的心力衰竭患者，以及服用其他与QT间期延长相关的药物的患者。在使用BRAFTOVI之前和期间，纠正低钾血症和低镁血症。Withhold, reduce dose, or permanently discontinue for QTc >500 ms.. QTc >500 ms时，应暂停、减量或永久停用。Embryo-Fetal Toxicity: 胚胎-胎儿毒性：BRAFTOVI can cause fetal harm when administered to pregnant women. BRAFTOVI can render hormonal contraceptives ineffective. Advise females of reproductive potential to use effective nonhormonal contraception during treatment with BRAFTOVI and for 2 weeks after the final dose. BRAFTOVI在给孕妇使用时可能会对胎儿造成伤害。BRAFTOVI可能使激素类避孕药无效。建议有生育潜力的女性在使用BRAFTOVI治疗期间以及最后一剂后的两周内使用有效的非激素类避孕措施。Risks Associated with Combination Treatment: 联合治疗相关的风险：BRAFTOVI is indicated for use as part of a regimen in combination with cetuximab and mFOLFOX6 or FOLFIRI. Refer to the prescribing information for cetuximab and individual product components of mFOLFOX6 and FOLFIRI for additional risk information. BRAFTOVI 联合西妥昔单抗以及 mFOLFOX6 或 FOLFIRI 方案使用时适用。有关更多信息，请参阅西妥昔单抗、mFOLFOX6 和 FOLFIRI 各自的产品说明书以获取额外的风险信息。Lactation: 泌乳：Advise women not to breastfeed during treatment with BRAFTOVI and for 2 weeks after the final dose. 建议女性在使用BRAFTOVI治疗期间以及最后一剂后的2周内不要进行母乳喂养。Infertility: 不孕不育：Advise males of reproductive potential that BRAFTOVI may impair fertility. 告知有生殖潜力的男性，BRAFTOVI可能会损害生育能力。ADVERSE REACTIONS 不良反应BRAF BRAFV600E V600Emutation-positive mCRC, in combination with cetuximab and mFOLFOX6 突变阳性的mCRC，联合使用西妥昔单抗和mFOLFOX6Serious adverse reactions 严重的不良反应occurred in 46% of patients who received BRAFTOVI in combination with cetuximab and mFOLFOX6. Serious adverse reactions in >3% of patients included intestinal obstruction (4.7%), pyrexia (3.9%), sepsis (3.4%), and abdominal pain (3.4%) 在接受BRAFTOVI联合西妥昔单抗和mFOLFOX6治疗的患者中，46%的患者发生了不良反应。超过3%的患者出现的严重不良反应包括肠梗阻（4.7%）、发热（3.9%）、败血症（3.4%）和腹痛（3.4%）。Fatal intestinal obstruction 致命性肠梗阻occurred in 0.9%, and 发生在0.9%，并且fatal large intestinal perforation and 致命的大肠穿孔和 gastrointestinal perforation 胃肠道穿孔occurred in 0.4% (each) in patients who received BRAFTOVI in combination with cetuximab and mFOLFOX6 在接受BRAFTOVI联合西妥昔单抗和mFOLFOX6治疗的患者中，各占0.4%。Most common adverse reactions 最常见的不良反应(≥25%, all grades) in the BRAFTOVI with cetuximab and mFOLFOX6 arm compared to the control arm (mFOLFOX6 ± bevacizumab or FOLFOXIRI ± bevacizumab or CAPOX ± bevacizumab), and a subset of the control arm (mFOLFOX6 ± bevacizumab), respectively were: peripheral neuropathy (64% vs 53% and 57%), nausea (54% vs 50% and 44%), fatigue (53% vs 41% and 45%), diarrhea (42% vs 50% and 44%), decreased appetite (38% vs 27% and 30%), rash (36% vs 6% and 5%), vomiting (36% vs 22% and 17%), hemorrhage (34% vs 21% and 15%), abdominal pain (32% vs 31% and 30%), arthralgia (32% vs 6% and 7%), pyrexia (29% vs 16% and 17%), and constipation (27% vs 23% and 25%). 在BRAFTOVI联合西妥昔单抗和mFOLFOX6组与对照组（mFOLFOX6 ± 贝伐珠单抗或FOLFOXIRI ± 贝伐珠单抗或CAPOX ± 贝伐珠单抗）以及对照组的一个子集（mFOLFOX6 ± 贝伐珠单抗）相比，分别出现以下不良反应（≥25%，所有级别）：外周神经病变（64% vs 53% 和 57%）、恶心（54% vs 50% 和 44%）、疲劳（53% vs 41% 和 45%）、腹泻（42% vs 50% 和 44%）、食欲减退（38% vs 27% 和 30%）、皮疹（36% vs 6% 和 5%）、呕吐（36% vs 22% 和 17%）、出血（34% vs 21% 和 15%）、腹痛（32% vs 31% 和 30%）、关节痛（32% vs 6% 和 7%）、发热（29% vs 16% 和 17%）以及便秘（27% vs 23% 和 25%）。Most common laboratory abnormalities 最常见的实验室异常(≥10%, grade 3 or 4) in the BRAFTOVI with cetuximab and mFOLFOX6 arm compared to the control arm (mFOLFOX6 ± bevacizumab or FOLFOXIRI ± bevacizumab or CAPOX ± bevacizumab), and a subset of the control arm (mFOLFOX6 ± bevacizumab), respectively were: increased lipase (53% vs 28% and 23%), decreased neutrophil count (37% vs 35% and 33%), decreased hemoglobin (19% vs 6% and 7%), decreased white blood cell count (12% vs 8% and 6%), and increased glucose (11% vs 2% and 1%). (≥10%，3级或4级) 在BRAFTOVI联合西妥昔单抗和mFOLFOX6组与对照组（mFOLFOX6 ± 贝伐珠单抗或FOLFOXIRI ± 贝伐珠单抗或CAPOX ± 贝伐珠单抗），以及对照组的一个子集（mFOLFOX6 ± 贝伐珠单抗）中，分别观察到以下不良反应：脂肪酶升高（53% vs 28% 和 23%）、中性粒细胞计数减少（37% vs 35% 和 33%）、血红蛋白减少（19% vs 6% 和 7%）、白细胞计数减少（12% vs 8% 和 6%）以及血糖升高（11% vs 2% 和 1%）。BRAF BRAFV600E mutation-positive mCRC, in combination with cetuximab and FOLFIRI V600E突变阳性的mCRC，联合使用西妥昔单抗和FOLFIRI方案Serious adverse reactions 严重的不良反应occurred in 39% of patients who received BRAFTOVI in combination with cetuximab and FOLFIRI. Serious adverse reactions in >3% of patients included febrile neutropenia (5.6%) and infusion related reaction (4.2%) 接受BRAFTOVI联合西妥昔单抗和FOLFIRI治疗的患者中，39%发生了不良反应。超过3%的患者出现的严重不良反应包括发热性中性粒细胞减少（5.6%）和输注相关反应（4.2%）。Fatal gastrointestinal perforation 致命的胃肠道穿孔occurred in 1.4% of patients who received BRAFTOVI in combination with cetuximab and FOLFIRI 在接受BRAFTOVI联合西妥昔单抗和FOLFIRI治疗的患者中，有1.4%的患者发生了该情况。Most common adverse reactions 最常见的不良反应(>25%, all grades) in the BRAFTOVI with cetuximab and FOLFIRI arm compared to the control arm (FOLFIRI ± bevacizumab) were nausea (61% vs 57%), diarrhea (55% vs 49%), fatigue (47% vs 50%), vomiting (47% vs 31%), alopecia (35% vs 22%), constipation (31% vs 29%), abdominal pain (30% vs 22%), decreased appetite (30% vs 32%), and rash (27% vs 1.5%). (>25%，所有等级) 在BRAFTOVI联合西妥昔单抗和FOLFIRI组相较于对照组（FOLFIRI ± 贝伐珠单抗）的不良反应为恶心（61% vs 57%）、腹泻（55% vs 49%）、疲劳（47% vs 50%）、呕吐（47% vs 31%）、脱发（35% vs 22%）、便秘（31% vs 29%）、腹痛（30% vs 22%）、食欲下降（30% vs 32%）以及皮疹（27% vs 1.5%）。Most common laboratory abnormalities 最常见的实验室异常(≥10%, grade 3 or 4) in the BRAFTOVI with cetuximab and FOLFIRI arm compared to the control arm (FOLFIRI ± bevacizumab) were: decreased neutrophil count (30% vs 32%), increased lipase (22% vs 12%), decreased white blood cell count (20% vs 6%), and decreased hemoglobin (10% vs 3%) （≥10%，3级或4级）在BRAFTOVI联合西妥昔单抗和FOLFIRI组与对照组（FOLFIRI ± 贝伐珠单抗）相比，分别为：中性粒细胞计数减少（30% vs 32%）、脂肪酶升高（22% vs 12%）、白细胞计数减少（20% vs 6%）和血红蛋白减少（10% vs 3%）。DRUG INTERACTIONS 药物相互作用Strong or moderate CYP3A4 inhibitors: 强效或中效CYP3A4抑制剂：Avoid coadministration of BRAFTOVI with strong or moderate CYP3A4 inhibitors, including grapefruit juice. If coadministration is unavoidable, reduce the BRAFTOVI dose. 避免将BRAFTOVI与强效或中效CYP3A4抑制剂（包括葡萄柚汁）同时使用。如果无法避免同时使用，应减少BRAFTOVI的剂量。Strong CYP3A4 inducers: 强效CYP3A4诱导剂：Avoid coadministration of BRAFTOVI with strong CYP3A4 inducers. 避免将BRAFTOVI与强效CYP3A4诱导剂联合使用。Sensitive CYP3A4 substrates: 敏感的CYP3A4底物：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. 避免将BRAFTOVI与CYP3A4底物（包括激素类避孕药）联合使用，因为血浆浓度的降低可能会导致底物疗效下降。如果无法避免联合使用，请参阅CYP3A4底物产品的标签说明以获取建议。Dose reductions of drugs that are 药物的剂量减少substrates of OATP1B1, OATP1B3, or BCRP OATP1B1、OATP1B3 或 BCRP 的底物may be required when used concomitantly with BRAFTOVI. 与BRAFTOVI同时使用时可能需要。Avoid coadministration of BRAFTOVI with 避免同时服用BRAFTOVI与drugs known to prolong QT/QTc interval. 已知会延长QT/QTc间期的药物。View the full Prescribing Information 查看完整的处方信息. 。There may be a delay as the document is updated with the latest information. It will be available as soon as possible. Please check back for the updated full information shortly. 可能会有延迟，因为文档正在更新为最新信息。我们将会尽快提供。请稍后查看完整的更新信息。About Pfizer Oncology 辉瑞肿瘤学简介At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and multispecific antibodies, including other immune-oncology biologics. 在辉瑞肿瘤事业部，我们正处于癌症治疗新时代的前沿。我们行业领先的资产组合和广泛的管线包括三种核心作用机制，从多个角度攻击癌症，包括小分子、抗体药物偶联物 (ADC) 和多特异性抗体，以及其他免疫肿瘤生物制品。We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, gastrointestinal cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives.. 我们专注于在一些全球最常见的癌症中提供变革性的治疗方法，包括乳腺癌、胃肠道癌、泌尿生殖系统癌、血液肿瘤学以及胸部癌症（包括肺癌）。受科学驱动，我们致力于加速突破，以帮助癌症患者过上更好、更长寿的生活。About Pfizer: Breakthroughs That Change Patients’ Lives 关于辉瑞：改变患者生活的突破性进展At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. 在辉瑞，我们运用科学和全球资源，为人们带来能够延长生命并显著改善生活的疗法。我们努力在医疗保健产品的研发、开发和生产过程中，为质量、安全性和价值树立标杆，包括创新药物和疫苗。Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. 每天，辉瑞的同事们都在发达市场和新兴市场开展工作，以促进健康、预防、治疗和攻克当今最令人恐惧的疾病。作为全球首屈一指的创新型生物制药公司之一，我们与医疗保健提供者、政府和当地社区合作，支持并扩大全球获得可靠且负担得起的医疗保健的机会。For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at . 175 年来，我们一直努力为我们所服务的所有人带来改变。我们经常在我们的网站上发布可能对投资者重要的信息。www.Pfizer.com www.Pfizer.com. In addition, to learn more, please visit us on 此外，要了解更多信息，请访问我们www.Pfizer.com www.Pfizer.comand follow us on X at 并在X上关注我们@Pfizer @辉瑞and 和@Pfizer News 辉瑞新闻, ，LinkedIn 领英, ，YouTube YouTubeand like us on Facebook at 并在Facebook上关注我们Facebook.com/Pfizer Facebook.com/辉瑞. 。Disclosure Notice 披露通知The information contained in this release is as of February 24, 2026. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. 本新闻稿中的信息截至2026年2月24日。辉瑞不对因新信息、未来事件或发展而更新本新闻稿中包含的前瞻性声明承担任何责任。This release contains forward-looking information about BRAFTOVI 本发布包含关于BRAFTOVI的前瞻性信息® ®(encorafenib) and an approval in the U.S. for BRAFTOVI in combination with cetuximab and fluorouracil-based chemotherapy for the treatment of adult patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, including their potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. （恩科拉非尼）以及在美国获得的BRAFTOVI与西妥昔单抗和基于氟尿嘧啶的化疗联合使用的批准，用于治疗携带BRAF V600E突变的成人转移性结直肠癌（mCRC）患者，包括其潜在益处，但涉及重大的风险和不确定性，可能导致实际结果与这些声明所表达或暗示的结果有重大差异。Risks and uncertainties include, among other things, uncertainties regarding the commercial success of BRAFTOVI plus cetuximab and fluorouracil-based chemotherapy; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when any drug applications may be filed in any additional jurisdictions for BRAFTOVI plus cetuximab and fluorouracil-based chemotherapy for the treatment of adult patients with metastatic CRC with a BRAF V600E mutation or in any jurisdictions for any other potential indications for BRAFTOVI; whether and when any such other applications may be approved by other regulatory authorities, which will depend on myriad factors, including making a determination as to whether the product's benefits outweigh its known risks and determination of the product's efficacy and, if approved, whether BRAFTOVI plus cetuximab and . 风险和不确定性包括但不限于以下方面：BRAFTOVI联合西妥昔单抗和基于氟尿嘧啶的化疗在商业上的成功存在不确定性；研发过程中的固有不确定性，包括是否能够达到预期的临床终点、临床试验的启动和/或完成日期、监管提交日期、监管批准日期和/或上市日期，以及可能出现不利的新临床数据并对现有临床数据进行进一步分析的可能性；临床试验数据可能因监管机构而有不同的解释和评估；监管机构是否会对我们的临床研究设计及结果感到满意；是否以及何时可以在任何其他司法管辖区提交BRAFTOVI联合西妥昔单抗和基于氟尿嘧啶的化疗用于治疗携带BRAF V600E突变的转移性结直肠癌（CRC）成人患者的药物申请，或者在任何司法管辖区针对BRAFTOVI的任何其他潜在适应症提交申请；是否以及何时会获得其他监管机构对任何此类其他申请的批准，这将取决于众多因素，包括确定产品的益处是否超过其已知风险，以及确定产品的疗效，如果获批，BRAFTOVI联合西妥昔单抗和…A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2024 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. 辉瑞公司在截至2024年12月31日的财政年度的Form 10-K年度报告以及其后续的Form 10-Q报告中，特别是在标题为“风险因素”和“前瞻性信息及可能影响未来结果的因素”的章节中，提供了对风险和不确定性的进一步描述。此外，相关信息也包含在其后续提交的Form 8-K报告中，所有这些报告均已提交给美国证券交易委员会。Securities and Exchange Commission and available at . 证券交易委员会，可访问。www.sec.gov www.sec.govand 和www.pfizer.com www.pfizer.com. 。ERBITUX ERBITUX® ®is a registered trademark of Eli Lilly and Company its subsidiaries, or affiliates. 是Eli Lilly and Company及其子公司或关联公司的注册商标。References 参考文献American Cancer Society. 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The prognostic value of BRAF mutation in colorectal cancer and melanoma: A systematic review and meta-analysis. Safaee Ardekani G, Jafarnejad SM, Tan L, 等。BRAF突变在结直肠癌和黑色素瘤中的预后价值：一项系统评价和荟萃分析。PloS ONE PLOS ONE. 2012;7(10):e47054. . 2012;7(10):e47054.Schirripa M, Biason P, Lonardi S, et al. Class 1, 2, and 3BRAF-Mutated Metastatic Colorectal Cancer: A Detailed Clinical, Pathologic, and Molecular Characterization. 斯奇里帕 M，比亚松 P，隆纳迪 S，等。1类、2类和3类BRAF突变转移性结直肠癌：详细的临床、病理和分子特征。 Clin Cancer Res 临床癌症研究. 2019;25(13):3954-3961. doi:10.1158/1078-0432.CCR-19-0311 . 2019;25(13):3954-3961. doi:10.1158/1078-0432.CCR-19-0311NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines NCCN临床实践指南：肿瘤学（NCCN指南）® ®) for Colon Cancer. V.5.2025 © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed November 2025. To view the most recent and complete version of the guideline, go online to NCCN.org. `) 适用于结肠癌。V.5.2025 © 国家综合癌症网络，Inc. 2024。保留所有权利。2025年11月访问。要查看最新和完整的指南版本，请访问NCCN.org。`Cervantes A, Adam R, Roselló S, et al. Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. 塞万提斯 A、亚当 R、罗塞洛 S 等。转移性结直肠癌：ESMO 临床实践指南，用于诊断、治疗和随访。Ann Oncol 肿瘤学年鉴. 2023;34(1):10–32. . 2023；34（1）：10–32。Media Contact: 媒体联系人： PfizerMediaRelations@Pfizer.com 辉瑞媒体关系@辉瑞.comInvestor Contact: 投资者联系方式： IR@Pfizer.com IR@Pfizer.comSource: Pfizer Inc. 来源：辉瑞公司