Cetuximab

“ 口咽癌作为头颈部常见恶性肿瘤之一，近年来在治疗策略和药物研发方面取得了显著进展。” 01 —政策环境：推动精准医疗与多学科协作1. 国家癌症防治行动增强 中国“健康中国2030”规划纲要持续推进，头颈肿瘤防治被纳入重点癌症防控范畴。2023年起，多个省市已将口咽癌早期筛查项目纳入地方公共卫生服务包，重点针对高危人群（长期吸烟、饮酒者及HPV感染人群）开展筛查。2. 医保政策优化 2024年国家医保目录调整中，新增了多项与口咽癌治疗相关的靶向药物和免疫检查点抑制剂，大幅降低了患者经济负担。部分省市还试点开展了“按疗效付费”的医保支付方式改革，对创新药物实行更灵活的报销政策。3. 临床研究鼓励政策 国家药监局药品审评中心（CDE）针对头颈肿瘤创新药物开辟了“突破性治疗药物程序”，加速临床急需药物的审评审批。同时，真实世界研究在口咽癌治疗评价中的应用获得政策认可，为药物研发提供了更高效的数据支持。 02 —治疗新策略：从标准化到个体化1. HPV阳性口咽癌的去强化治疗趋势 随着人乳头瘤病毒（HPV）相关口咽癌发病率上升，全球多项临床研究证实这类患者预后较好。目前研究重点转向“治疗减毒”策略，旨在保持疗效的同时降低治疗毒性。2023年发表的多项研究显示，对早期HPV阳性口咽癌，减少化疗剂量或采用单纯放疗可能达到与传统方案相当的疗效，但生活质量显著提高。2. 保功能手术技术进步 经口机器人手术（TORS）和激光显微手术的普及，使更多口咽癌患者能够在完全切除肿瘤的同时，保留吞咽、语言等重要功能。国内多家肿瘤中心已将该技术纳入标准治疗方案，并开展了针对性培训项目。 03 —药物研发进展：靶向与免疫治疗突破1. 免疫检查点抑制剂应用拓展 帕博利珠单抗（pembrolizumab）和纳武利尤单抗（nivolumab）等PD-1抑制剂在复发/转移性头颈鳞癌（包括口咽癌）的一线治疗地位已确立。最新研究聚焦于： 联合治疗策略：免疫药物与靶向药物、化疗或放疗的联合方案，如2024年ASCO年会上报告的免疫疗法联合西妥昔单抗在HPV阴性口咽癌中的研究数据 生物标志物优化：除PD-L1表达外，肿瘤突变负荷（TMB）和基因表达特征等新型生物标志物的探索2. 新型靶向药物进展 EGFR双重靶点抑制剂：新一代EGFR/HER3双特异性抗体药物在临床试验中显示出潜力，可能克服对传统EGFR抑制剂的耐药PI3K通路抑制剂：针对PI3KCA突变的口咽癌患者，特异性抑制剂的研究已进入II期临床抗肿瘤血管生成药物：与免疫疗法联合使用，改变肿瘤微环境，增强治疗效果3. 治疗性HPV疫苗 针对HPV阳性口咽癌的治疗性疫苗研发取得阶段性成果。与预防性疫苗不同，治疗性疫苗旨在激活机体对已感染HPV及癌细胞的免疫反应。多种疫苗平台（DNA疫苗、多肽疫苗、病毒载体疫苗）处于临床前或早期临床研究阶段。4. ADC药物崭露头角 抗体药物偶联物（ADC）在口咽癌治疗中展现出前景。靶向EGFR、HER2等靶点的ADC药物，能够精准递送细胞毒性药物至肿瘤细胞，在临床试验中显示出对传统治疗耐药患者的活性。 04 —支持性治疗创新1. 精准放疗技术 质子治疗和碳离子治疗在国内逐步推广，对于邻近关键结构的口咽癌，这些技术能够更精确地靶向肿瘤，减少对周围正常组织的损伤。2. 人工智能辅助诊疗 AI技术在口咽癌影像诊断、靶区勾画、预后预测等方面的应用日益成熟。国内多家医疗中心开发了专门针对口咽癌的AI辅助系统，提高了诊断准确性和治疗规划效率。3. 康复治疗整合 多学科康复团队成为口咽癌标准治疗的一部分，包括语言治疗师、营养师、心理医生等，全程管理患者的吞咽功能、营养状况和心理适应。 05 —未来展望与挑战 口咽癌治疗正迈向更加精准、个性化的新时代，但仍面临诸多挑战： HPV阳性和阴性口咽癌在生物学行为和治疗反应上的差异需要更深入理解 免疫治疗耐药机制及应对策略亟待突破 长期幸存者的生活质量管理需要系统化方案 06 —患者行动建议 口咽癌治疗领域的快速进展为患者带来了新希望。随着政策支持力度加大和创新药物不断涌现，个体化、精准化的治疗模式正在逐步成为现实，有望进一步提高口咽癌的治愈率和患者生活质量。 高危人群应定期进行口腔及咽喉检查 确诊患者应在大型肿瘤中心寻求多学科团队诊疗 积极参与临床研究，尤其当标准治疗效果有限时 治疗期间及治疗后重视功能康复和生活质量维护

On February 24, 2026, the Food and Drug Administration granted traditional approval to encorafenib (Braftovi, Array BioPharma Inc., a subsidiary of Pfizer Inc.) in combination with cetuximab and fluorouracil-based chemotherapy for the treatment of adult patients with metastatic colorectal cancer (CRC) with a BRAF V600E mutation, as detected by an FDA-authorized test. Encorafenib received accelerated approval in combination with cetuximab and mFOLFOX6 for metastatic colorectal cancer with BRAF V600E mutation in 2024.Full prescribing information for Braftovi will be posted on Drugs@FDA.Efficacy and SafetyEfficacy was evaluated in the BREAKWATER trial (NCT04607421), a randomized, active-controlled, open-label, multicenter trial in patients with treatment-naïve, BRAF V600E mutation–positive, metastatic CRC, as detected using the Qiagen “therascreen BRAF V600E RGQ PCR Kit.” The Phase 3 portion of BREAKWATER initially randomized 1:1:1 to one of the following three arms:encorafenib orally once daily with cetuximab IV infusion every 2 weeks (experimental, Arm A),encorafenib orally once daily with cetuximab IV infusion every 2 weeks and mFOLFOX6 every 2 weeks (experimental, Arm B), ormFOLFOX6 or FOLFOXIRI (both every 2 weeks) or CAPOX (every 3 weeks), each with or without bevacizumab (control, Arm C).The trial was subsequently amended to limit randomization (1:1) to Arm B and Arm C, and a new cohort was initiated, Cohort 3, with the following two treatment arms, randomized 1:1:encorafenib orally once daily with cetuximab IV infusion every 2 weeks and FOLFIRI every 2 weeks (experimental, Arm D), orFOLFIRI every 2 weeks, with or without bevacizumab (control, Arm E).Treatment in all arms continued until disease progression, unacceptable toxicity, consent withdrawal, loss to follow-up, or death.Phase 3 Portion of BREAKWATERThe major efficacy outcome measures were progression-free survival (PFS) in all randomized patients and objective response rate (ORR) in the first 110 patients randomized in each arm per blinded, independent, central review (BICR). Overall survival in all patients was an additional formally tested outcome measure. A total of 236 patients were randomized to the investigational Arm B and 243 to the control, Arm C.Median PFS was 12.8 months (95% CI: 11.2, 15.9) in Arm B and 7.1 months (95% CI: 6.8, 8.5) in Arm C (hazard ratio [HR] 0.53 [95% CI: 0.41, 0.68]; p-value <0.0001). Median OS was 30.3 months (95% CI: 21.7, NE) and 15.1 months (95% CI: 13.7, 17.7) (HR 0.49 [95% CI: 0.38, 0.63), respectively; p-value <0.0001). ORR was 61% (95% CI: 52%, 70%) and 40% (95% CI: 31%, 49%) (p-value = 0.0008) in the respective arms.Cohort 3 Portion of BREAKWATERThe major efficacy outcome measure was ORR per BICR; 73 patients were randomized to investigational Arm D and 74 to the control, Arm E. The ORR was 64% (95% CI: 53, 74) in Arm D, compared to 39% (95% CI: 29, 51) in Arm E (p-value = 0.0011).Warnings and PrecautionsThe prescribing information includes warnings and precautions for new primary malignancies (cutaneous and noncutaneous), tumor promotion in BRAF–wild-type tumors, cardiomyopathy, hepatotoxicity, hemorrhage, uveitis, QT prolongation, and embryo-fetal toxicity.The recommended encorafenib dose is 300 mg (four 75 mg capsules) orally once daily in combination with cetuximab and mFOLFOX6 or in combination with cetuximab and FOLFIRI until disease progression or unacceptable toxicity. Full dosing information is provided in the prescribing information.Project Frontrunner and Project OrbisThis application is an example of the Oncology Center of Excellence’s Project FrontRunner aimed at providing earlier access to therapies in earlier disease settings.This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with Health Canada. The application reviews are ongoing at the other regulatory agencies.This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.govOncProjectFacilitate@fda.hhs.gov.Follow the Oncology Center of Excellence on X: @FDAOncology.