Tremelimumab

Positive high-level results from the final overall survival (OS) analysis of the FLAURA2 Phase III trial showed AstraZeneca’s Tagrisso (osimertinib) with the addition of pemetrexed and platinum-based chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the key secondary endpoint of OS compared to Tagrisso monotherapy for patients with 1st-line locally advanced or metastatic epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC).​ The final OS analysis demonstrates consistent survival benefit as previously reported in the interim OS results, and builds on the previously presented primary endpoint data, which demonstrated the longest-reported median progression-free survival (PFS) in this setting. Pasi A. Jänne, MD, PhD, Senior Vice President for Translational Medicine and thoracic medical oncologist at Dana-Farber Cancer Institute and principal investigator for the FLAURA2 trial, said: “When treating lung cancer, the aim is to both prolong survival and improve the patient experience, especially in 1st-line where treatment duration can be long and many patients remain active. These positive results support osimertinib, either as monotherapy or in combination with chemotherapy, as standard of care for patients with 1st-line advanced EGFR-mutated lung cancer and reinforce the meaningful benefit of the combination in the current clinical setting. The observed survival benefit is particularly impressive given that FLAURA2 did not impose any restrictions on the choice of subsequent treatment after disease progression.” Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “These exciting overall survival results add to the extensive evidence supporting Tagrisso as the backbone therapy in EGFR-mutated lung cancer, demonstrating that Tagrisso plus chemotherapy can significantly extend survival in the 1st-line advanced setting, in addition to prior trials showing survival benefits as monotherapy in both early stage and advanced disease. With its strong survival benefit and tolerable safety profile, this combination has the potential to help patients live longer while maintaining their quality of life on treatment.” With longer follow up, the safety profile of Tagrisso plus chemotherapy continues to be manageable and consistent with the established profiles of the individual medicines. Adverse event (AE) rates were higher in the Tagrisso plus chemotherapy arm, driven by well-characterised chemotherapy-related AEs. Discontinuation rates due to AEs and on-target toxicities were low in both arms of the trial. These data will be presented at a forthcoming medical meeting and shared with global regulatory authorities. Tagrisso plus chemotherapy is approved in more than 80 countries, including the US, EU, China and Japan, based on the FLAURA2 Phase III trial. Notes NSCLC Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into small cell lung cancer or NSCLC, the latter accounting for 80-85% of cases.1-2 Approximately 75% of people are diagnosed with advanced NSCLC.3 Additionally, about 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.4-6 While EGFR-tyrosine kinase inhibitors (TKI) have significantly improved outcomes in the 1st-line setting, mechanisms of resistance and disease progression are extremely common, and a significant unmet need exists in later-line settings for effective and well-tolerated treatment options.7-10 FLAURA2 FLAURA2 is a randomised, open-label, multi-centre, global Phase III trial in the 1st-line treatment of patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) EGFRm NSCLC. Patients were treated with Tagrisso 80mg QD oral tablets with the addition of chemotherapy (pemetrexed (500mg/m2) plus cisplatin (75mg/m2) or carboplatin (AUC5) every three weeks for four cycles, followed by Tagrisso with pemetrexed maintenance every three weeks. The trial enrolled 557 patients in more than 150 centres across more than 20 countries, including in the US, Europe, South America and Asia. The primary endpoint is PFS with OS as the key secondary endpoint. Tagrisso Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system metastases. Tagrisso (40mg and 80mg QD oral tablets) has been used to treat more than one million patients across its indications worldwide and AstraZeneca continues to explore Tagrisso as a treatment for patients across multiple stages of EGFRm NSCLC. Tagrisso is approved as monotherapy in more than 120 countries including the US, EU, China and Japan. Approved indications include for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC, locally advanced or metastatic EGFR T790M mutation-positive NSCLC, adjuvant treatment of early-stage EGFRm NSCLC and locally advanced, unresectable NSCLC following platinum-based chemoradiation therapy (CRT). Tagrisso plus chemotherapy is approved in more than 80 countries, including the US, EU, China and Japan, for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC. There is an extensive body of evidence supporting the use of Tagrisso in EGFRm NSCLC. Tagrisso is the only targeted therapy shown to improve patient outcomes in early-stage disease in the NeoADAURA and ADAURA Phase III trials, locally advanced stages in the LAURA Phase III trial and late-stage disease in the FLAURA and FLAURA2 Phase III trials. As part of AstraZeneca’s ongoing commitment to treating patients as early as possible in lung cancer, Tagrisso is also being investigated in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial. AstraZeneca in lung cancer AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most. The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including Tagrisso and Iressa (gefitinib); Imfinzi (durvalumab) and Imjudo (tremelimumab); Enhertu (trastuzumab deruxtecan) and Datroway (datopotamab deruxtecan) in collaboration with Daiichi Sankyo; Orpathys (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action. AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment. AstraZeneca in oncology AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients. The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience. AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death. AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca. Contacts For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here. References 1. World Health Organization. International Agency for Research on Cancer. Lung Cancer Fact Sheet. Available at: https://gco-iarc-who-int.libproxy1.nus.edu.sg/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf. Accessed July 2025. 2. American Cancer Society. What Is Lung Cancer?. https://www.cancer.org/cancer/types/lung-cancer/about/what-is.html. Accessed July 2025. 3. Chen HJ, et al. Long-term survival of advanced lung adenocarcinoma by maintenance chemotherapy followed by EGFR-TKI. Medicine. 2021;100(6):e24688. 4. Keedy VL, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011:29;2121-27. 5. Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on Cytological and Histological Samples in Non-Small Cell Lung Cancer: a Polish, Single Institution Study and Systematic Review of European Incidence. Int J Clin Exp Pathol. 2013;6:2800-2812. 6. Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a Review of Available Methods and Their Use for Analysis of Tumour Tissue and Cytology Samples. J Clin Pathol. 2013;66:79-89. 7. Chen R, et al. Emerging therapeutic agents for advanced non-small cell lung cancer. J Hematol Oncol. 2020;13(1):58. 8. Majeed U, et al. Targeted therapy in advanced non-small cell lung cancer: current advances and future trends. J Hematol Oncol. 2021;14(1):108. 9. Morgillo F, et al. Mechanisms of resistance to EGFR-targeted drugs: lung cancer. ESMO Open. 2016;1(3):e000060. 10. Han B, et al. Efficacy of pemetrexed-based regimens in advanced non-small cell lung cancer patients with activating epidermal growth factor receptor mutations after tyrosine kinase inhibitor failure: a systematic review. Onco Targets Ther. 2018;11:2121-2129. Oncology Corporate and financial

编者按：近年来，肝癌治疗领域正经历一场深刻变革——局部治疗与系统治疗的联合策略逐渐成为研究热点。作为肝癌综合治疗的重要组成部分，经导管动脉化疗栓塞术（TACE）与靶向治疗、免疫治疗的协同作用机制备受关注。TACE联合系统治疗的三大里程碑研究——EMERALD-1、LEAP-012和TALENTACE研究结果正在重塑临床实践格局，它们从不同角度探索了联合治疗的最佳模式，为临床决策提供了重要依据。在APPLE 2025会议上，肝癌领域权威专家、日本近畿大学医学院Masatoshi Kudo教授接受了本刊的专访，对这一领域的最新探索进行了深度解读。Kudo教授在访谈中重点剖析了这三项研究的设计特点与临床意义，特别强调了治疗时机选择、药物组合优化，以及个体化治疗的重要性。01《肿瘤瞭望》：TACE与系统治疗联合方案在肝癌治疗领域一直是备受瞩目的研究方向。TALENTACE、EMERALD-1和LEAP-012这三项研究作为该领域的近期重要成果，为我们带来了很多新的见解。能否请您先总体评价一下这三项研究对于推动TACE联合系统治疗在肝癌临床应用上的重要意义？Masatoshi Kudo 教授日本近畿大学医学院在肝癌治疗领域，EMERALD-1、LEAP-012与TALENTACE三项研究意义重大，不过在试验设计与结果呈现上各有特点。从研究结果来看，EMERALD-1试验显示，相较于单纯TACE治疗，度伐利尤单抗联合贝伐珠单抗再联合TACE可显著延长患者无进展生存期（PFS），风险比（HR）为0.77。LEAP-012研究中，仑伐替尼联合帕博利珠单抗再联合TACE，较单纯TACE改善了PFS，HR为0.66。TALENTACE研究中，TACE联合阿替利珠单抗和贝伐珠单抗使PFS延长，HR为0.71，且该结果与RESIST v1.1研究（HR = 0.64）均具统计学显著性。目前，这三项研究的生存期（OS）数据均不成熟，有待进一步随访。试验设计方面，EMERALD-1研究存在局限。该研究在TACE治疗期间，仅度伐利尤单抗与TACE联合，贝伐珠单抗未在TACE同期使用，即度伐利尤单抗单药治疗组在后续仅持续用该药。如此设计，因TACE期间缺乏抗VEGF药物联合，效果或非最优。LEAP-012研究则采用截然不同的设计，在首次TACE治疗前2-4周，预先给予仑伐替尼联合帕博利珠单抗。这使得该研究PFS差异在早期就显著体现，相比较EMERALD-1研究则不然。从临床实践考量，预先联合仑伐替尼、抗VEGF药物以及PD-1/PD-L1抑制剂的方案更具优势。TALENTACE研究先开展TACE治疗，随后使用阿替利珠单抗和贝伐珠单抗。综合来看，若临床实践中需采用类似LEAP-012研究的预先联合用药的设计，同时联用抗VEGF药物，可能是更优策略。02《肿瘤瞭望》：从已公布的数据来看，这三项研究在主要疗效指标上存在一定差异。您认为造成这些疗效差异的关键因素有哪些，是研究设计、患者基线特征，还是所使用的系统治疗药物不同？Masatoshi Kudo 教授日本近畿大学医学院个人认为造成这些疗效差异的关键因素涵盖研究设计、患者基线特征以及所使用的系统治疗药物等多个方面。研究设计对差异存在影响。正如我所说，在EMERALD-1研究中，TACE治疗期间未使用抗VEGF药物。而TACE会释放VEGF，VEGF会抑制CD8阳性T细胞，并上调调节性T细胞（T-reg）、髓源性抑制细胞（MDSC）或肿瘤相关巨噬细胞（TAM）等免疫抑制细胞。因此，该研究设计存在不足。TALENTACE研究是先进行TACE治疗，之后才开始使用阿替利珠单抗和贝伐珠单抗。相反，在LEAP-012研究中，预先使用仑伐替尼改善了TACE的疗效。由此可见，抗VEGF药物的预先作用或者同步使用至关重要。其次，分层因素也极为重要。LEAP-012研究引入了白蛋白-胆红素（ALBI）分级和肿瘤负荷评分这两个分层因素，它们与甲胎蛋白（AFP）值和体能状态一样，都是预后因素，这些分层因素会对研究结果产生影响。此外，患者基线特征也是造成差异的原因之一。EMERALD-1研究纳入了血管侵犯1级（VP1）、血管侵犯2级（VP2）的患者，这与其他研究在患者基线特征上存在细微差异。03《肿瘤瞭望》：从不良反应的发生率、严重程度等方面分析，您觉得哪种联合方案在安全性上更具优势？在临床实践中，我们如何根据患者的具体情况来平衡疗效和安全性，选择最合适的联合治疗方案？Masatoshi Kudo 教授日本近畿大学医学院从不良反应的发生率和严重程度等方面来评判安全性颇为困难，因为TACE的操作方式因国家和医疗机构而异。载药微球栓塞（DEB-TACE）与传统TACE（c-TACE）存在差异，c-TACE引发的不良反应更多，而DEB-TACE相对更安全。所以，安全性问题不能仅由系统治疗药物来判定。个人认为安全性并非关键问题，因为在真实世界实践中，以日本为例，我们采用仑伐替尼联合TACE序贯治疗，或阿替利珠单抗和贝伐珠单抗联合TACE治疗，并未察觉到明显的安全性隐患。重要的是，仑伐替尼与TACE联用可提升TACE的疗效，而贝伐珠单抗对TACE疗效的提升作用并不显著。尽管贝伐珠单抗具有抗VEGF效应，但它是一种抗体类药物，在最后一次注射贝伐珠单抗后，需等待约两周，其体内抗VEGF的血液浓度才会有所降低。相比之下，个人认为仑伐替尼更为有效。从这个角度看，仑伐替尼联合帕博利珠单抗再联合TACE（即LEAP-012研究的联合方案）或许是最佳组合。当然，阿替利珠单抗和贝伐珠单抗联合TACE治疗也具有一定疗效。不过，EMERALD-1研究的设计存在不足，为此，相关公司已启动EMERALD-3研究，该研究借鉴了LEAP-012的研究设计，采用仑伐替尼联合STRIDE方案（度伐利尤单抗联合曲美木单抗）再联合TACE，且在首次TACE前一周就开始使用仑伐替尼和STRIDE方案。EMERALD-3研究的结果即将公布，其研究设计也更为合理，有望取得成功。综上所述，个人认为仑伐替尼疗效良好，仑伐替尼联合TACE（len-TACE）这种组合十分出色。而且，PD-1/PD-L1药物与len-TACE具有协同效应。在临床实践中，我们可根据患者的具体情况，如肿瘤特征、体能状态、合并症等，在充分评估疗效和安全性的基础上，选择最合适的联合治疗方案。04《肿瘤瞭望》：综合这三项研究的结果，您对未来TACE与系统治疗联合方案在肝癌治疗中的发展方向有怎样的展望？Masatoshi Kudo 教授日本近畿大学医学院综合这三项研究的结果，个人认为未来TACE与系统治疗联合方案在肝癌治疗领域的发展方向值得期待。就研究设计而言，个人认为TALENTACE研究的设计更具优势。在EMERALD-1和LEAP-012研究中，首次疾病进展后，试验组便停止了既定方案治疗，后续治疗可能才在两个组别中引入，这使得从临床试验中观察到的疗效不够显著。而TALENTACE研究则不同，直至出现不可控制的疾病进展，阿替利珠单抗和贝伐珠单抗的既定方案治疗才会持续进行，同时按需实施TACE治疗。在实际临床应用中，一旦相关药物获批，我们或许可以采取这样的治疗策略：首次疾病进展后，继续使用抗血管内皮生长因子酪氨酸激酶抑制剂（抗VEGF-TKI）联合PD-1/PD-L1抗体进行治疗，即便出现新发病灶，即第二次疾病进展时，仍可继续该联合方案。这是因为TACE治疗会改变肿瘤微环境，在此情况下，原有的联合治疗方案可能再次发挥疗效。这种治疗模式有望成为未来肝癌治疗的理想方案。Masatoshi Kudo 教授日本近畿大学医学院胃肠病学和肝脏病学系主任国际肝癌协会（ILCA）创始理事、理事亚太原发性肝癌专家（APPLE）会议主席（2015-2017）美国肝脏疾病研究协会（AASLD）肝胆恶性肿瘤特别兴趣小组指导委员会成员日本肝癌指南编委会主席Liver Cancer杂志主编平台申明：此文章内容根据专家采访整理，仅代表专家个人观点。（来源：《肿瘤瞭望》编辑部）声 明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。