Doxorubicin Hydrochloride

– Approval Based on Positive Results from the Phase 3 HD21 Trial for Stage IIb with Risk Factors/III/IV Hodgkin Lymphoma – ADCETRIS-based Combination Demonstrated Superior Safety Profile and Efficacy Compared to eBEACOPP, a Standard of Care Regimen in Europe – Second Approval in Frontline Hodgkin Lymphoma Broadens ADCETRIS’ Therapeutic Reach, Adding to Six Previously Approved, Distinct Indications for ADCETRIS in the European Union OSAKA, Japan & CAMBRIDGE, MA, USA I June 03, 2025 I Takeda ( TSE:4502/NYSE:TAK ) today announced that the European Commission (EC) approved ADCETRIS ® (brentuximab vedotin) in combination with etoposide, cyclophosphamide, doxorubicin, dacarbazine and dexamethasone (ECADD) – a chemotherapy regimen – in adult patients with newly diagnosed Stage IIb with risk factors/III/IV Hodgkin lymphoma. The decision follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) on April 25, 2025. The approval for this ADCETRIS-based combination regimen, known as BrECADD, in frontline Hodgkin lymphoma is based on the results of the randomized Phase 3 HD21 trial. The study met its co-primary safety and efficacy endpoints, with BrECADD demonstrating significantly superior safety as assessed by treatment-related morbidity (TRMB) and non-inferior progression-free survival (PFS) in comparison to escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (eBEACOPP), a standard of care treatment in Europe 1 . “Today’s approval represents a significant advancement for patients with Hodgkin lymphoma in the European Union,” said Teresa Bitetti, president of the Global Oncology Business Unit at Takeda. “This approval reinforces the role of ADCETRIS as a backbone in the treatment of specific lymphomas, offering healthcare professionals greater flexibility to tailor treatment plans according to individual patient needs. We’re proud to contribute another impactful option for those diagnosed with this challenging disease.” ADCETRIS is an antibody-drug conjugate (ADC) directed at CD30, a defining marker of Hodgkin lymphoma, and has been previously approved as a therapy for adult patients in the European Union (EU) in six distinct indications. This decision marks the second approval for an ADCETRIS-based combination regimen for frontline Hodgkin lymphoma, broadening the spectrum of available treatments for patients who historically have had limited options. “With BrECADD, patients now have a treatment option that not only offers greater curative potential 2* but also significantly reduces treatment-related morbidity compared to eBEACOPP,” said Peter Borchmann, MD, PhD, University Hospital of Cologne, Germany, and trial chairman of the HD21 study. “This new ADCETRIS-based combination therapy may offer a new standard of care for frontline treatment of adults with advanced stage Hodgkin lymphoma, contributing to improved long-term outcomes for patients.” About the HD21 Trial The HD21 study is a Phase 3, multi-country, prospective, open-label, randomized, multicenter trial conducted by the German Hodgkin Study Group (GHSG) with a PET-response adapted designed to assess the feasibility, efficacy, safety and tolerability of BrECADD, a novel, rationally designed, CD30-intensified frontline regimen for patients with advanced Hodgkin lymphoma. Enrolled patients with newly diagnosed, Stage IIb with large mediastinal mass and/or extranodal lesions, Stage III or IV Hodgkin lymphoma were randomized to receive two cycles of either escalated BEACOPP or BrECADD, respectively, followed by interim PET staging. A decision is then made if patients received a further two or four cycles of escalated BEACOPP or BrECADD. The HD21 trial aims to evaluate a new treatment regimen to minimize side effects, while maintaining similar responses to treatment. The study has co-primary endpoints: safety is assessed by treatment-related morbidity (TRMB) (superiority), a novel endpoint focused on clinically relevant, acute toxicities of primary chemotherapy, and efficacy is assessed by PFS (non-inferiority). Secondary endpoints are tumor response (complete response [CR] rate), overall survival (OS), infertility rate at one year, second malignancies, frequency of adverse events, therapy adherence and quality of life. About ADCETRIS® (brentuximab vedotin) ADCETRIS is an antibody-drug conjugate (ADC) comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Pfizer’s proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-positive tumor cells. ADCETRIS injection for intravenous infusion has received FDA approval for eight indications: Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-autologous stem cell transplantation (ASCT) consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression in 2017, adults with pcALCL or CD30-expressing MF who have had prior systemic therapy in 2018, for previously untreated Stage IV Hodgkin lymphoma in combination with doxorubicin, vinblastine, and dacarbazine in 2019, and for previously untreated adult patients with sALCL, peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) or angioimmunoblastic T-cell lymphoma (AITL), whose tumors express CD30, in combination with cyclophosphamide, doxorubicin, prednisone in 2019. ADCETRIS received conditional marketing authorization from the European Commission in October 2012, and the specific obligations of the conditional marketing authorization were fulfilled in May 2022. The approved indications in the European Union are: (1) for the treatment of adult patients with previously untreated CD30-positive Stage III or IV Hodgkin lymphoma in combination with doxorubicin, vinblastine and dacarbazine (AVD), (2) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, (3) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (4) for the treatment of adult patients with relapsed or refractory sALCL, (5) for the treatment of adult patients with previously untreated sALCL in combination with CHP, (6) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy and (7) for the treatment of adult patients with previously untreated CD30+ Stage IIB with risk factors, Stage III or Stage IV HL in combination with etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone (BrECADD). ADCETRIS has received marketing authorization by regulatory authorities in 80 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See Important Safety Information below. ADCETRIS is being evaluated broadly in more than 70 clinical trials, including a Phase 3 study in first-line Hodgkin lymphoma (ECHELON-1) and another Phase 3 study in first-line CD30-positive peripheral T-cell lymphomas (ECHELON-2), as well as trials in many additional types of CD30-positive malignancies. Pfizer and Takeda fund joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs. Please see the full Prescribing Information, including BOXED WARNING, for ADCETRIS here . About Takeda Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit www.takeda.com . Medical Information This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development. Footnotes: *While late relapse is rare, PFS status after 5 years does not guarantee cure. Patients should be monitored and encouraged to report any return of symptoms as appropriate. References: SOURCE: Takeda Pharmaceutical

编者按：随着精准治疗的发展，早期乳腺癌患者的预后得到较大改善。不同亚型乳腺癌的早期治疗策略和研究进展各有特色，如TNBC的焦点在于如何使化疗方案更加优化，而HR+/HER2-乳腺癌的关注点在于通过CDK4/6i强化辅助治疗降低复发风险；HER2+乳腺癌则开始讨论如何进行精细化的降阶梯治疗。本次ASCO大会早期乳腺癌领域有哪些重要研究进展？《肿瘤瞭望》特邀复旦大学附属肿瘤医院邵志敏教授分享如下。eTNBC：卡铂早期治疗如何克服毒副作用和精准筛选人群《肿瘤瞭望》：本次ASCO大会的早期乳腺癌Rapid oral专场中，有多项TNBC（新）辅助治疗的研究公布，能否与我们分享一下这些最新研究进展及其临床启示？邵志敏 教授复旦大学附属肿瘤医院在TNBC领域，含铂辅助化疗的价值是临床热议话题之一，我们团队2021年发表于JAMA oncology的PATTERN研究已经证实，PCb（紫杉联合卡铂）可相较于CEF-T（环磷酰胺＋表柔比星＋氟尿嘧啶）显著提高无病生存率（5年DFS：86.5% vs 80.3%，HR 0.65，P=0.03）[1]。这次ASCO大会报道的III期NRG-BR003研究[2]显示，对于淋巴结阳性或淋巴结阴性的高危TNBC患者，在AC-wP（多柔比星/环磷酰胺序贯紫杉醇）基础上加入卡铂，并不能改善侵袭性无病生存期（5年IDFS：82.7% vs 77.8%，HR 0.78，P=0.18）。需注意的是，该研究中AC-wP＋Carbo方案显著增加了毒副作用，≥3级不良事件发生率达72.9%（对照组为51.1%），如果采用剂量密集方案是否能够降低不良反应发生率从而改善治疗获益，未来值得探讨。此外，个别亚组也显示了一定的获益趋势，如pN2（HR 0.52）和BRCA突变（HR 0.388），可进一步筛选和验证优势获益人群。△NRG-BR003研究IDFS及不良反应（左右滑动查看）本次ASCO大会同场报道的II期ABCSG 45研究[3]也部分验证了这一点。该研究针对HRD阳性的早期TNBC患者，分别使用传统化疗（TAC）或卡铂＋PAPR抑制剂新辅助治疗，结果显示尽管总体人群和BRCA野生型患者中，TAC组的RCB0/I率和pCR率均高于卡铂组，但在BRCA突变患者中，卡铂组的RCB0/I率（77.3% vs 65.0%）和pCR率（77.3% vs 65.0%）在数值上有所提升；此外，卡铂组显示更高的血液毒性，但非血液毒性更低，可见血液毒性仍是卡铂临床应用和管理的重要问题。△ABCSG 45研究：总体人群（HRD+）和BRCA突变状态患者的RCB0/I率和pCR率及安全性汇总（左右滑动查看）近年来，新型抗体偶联药物（ADC）似乎有增效、减毒的优势，在晚期治疗领域显示优于化疗的效果，有取代化疗的趋势。这次ASCO大会报道II期NeoSTAR研究[4]提供了一种新的TNBC早期治疗思路：术前使用TROP2 ADC戈沙妥珠单抗联合帕博利珠单抗新辅助治疗，4个周期后评估没有残存疾病则直接手术，有残存疾病则改用化疗。研究结果显示有34%的pCR。当然，这只是一项单臂研究，能否更换用药顺序使用化疗序贯ADC？ADC和化疗的最佳疗程一定是4个周期吗？是否有生物标志物可以筛选出ADC序贯化疗的优势人群？这些问题都值得进一步探讨。△NeoSTAR研究设计及和pCR、安全性结果（左右滑动查看）HR+ /HER2- eBCCD4/6i辅助治疗再添中国“达”案《肿瘤瞭望》：CDK4/6i辅助治疗是HR+早期乳腺癌领域的讨论热点。在本场口头报告中，您也汇报了DAWNA-A研究结果。能否为我们介绍一下这个领域的研究进展？邵志敏 教授复旦大学附属肿瘤医院近年来，已有两项CDK4/6i用于HR+/HER2-早期乳腺癌辅助治疗获得阳性结果的III期临床试验，即monarchE、NATALEE研究。这些研究的入组条件，用药方案均有所差异。我们开展的III期DAWNA-A研究[5]，使用的是国产CDK4/6i达尔西利。入组患者为≥4枚阳性腋结（ALNs），或1-3枚ALNs且存在≥1个以下高危因素：T≥5cm，组织学3级，新辅助治疗后残存浸润性乳腺癌，Ki-67≥30%。总体上与monarchE研究较为相似，但增加了新辅助non-pCR的患者。本研究中，达尔西利辅助治疗（125mg qd D1-21；Q4w）的疗程同样为2年，辅助内分泌治疗为标准≥5年。△DAWNA-A研究设计研究结果显示达到了主要终点，达尔西利组的2年IDFS率提高4.5%（94.7% vs 90.2%；HR 0.56，95%CI：0.43~0.71，P＜0.0001），且不同亚组获益趋势一致。DFS（HR 0.53，2年提高5.2%）和无远处转移生存期（DDFS，HR 0.60，2年提高3.8%）也显示达尔西利组获益。达尔西利的治疗安全性和耐受性尚可，两组药物导致的停药（2.1% vs 0.8%）和严重不良事件（3.7% vs 1.5%）发生率相当。DAWNA-A研究为达尔西利用于高危HR+/HER2-乳腺癌辅助治疗提供高质量循证医学证据，也为中国乳腺癌患者提供了新的CDK4/6i辅助治疗选择。△DAWNA-A研究主要终点IDFS及亚组分析、DFS/DDFS、安全性（左右滑动查看）绝经前尤其是年轻乳腺癌患者可能具有更高的复发风险，往往需要接受强化辅助内分泌治疗。本次ASCO大会报道了SOFT/TEXT研究[6]随访15年的数据显示，依西美坦＋OFS（OFS）的15年IDFS高于他莫昔芬＋OFS（TAM＋OFS）（74.9% vs 71.3%，HR 0.82），显示了AI＋OFS的持续获益，但也需看到15年时患者仍有将近25%~30%的疾病复发风险。本次ASCO大会上也报道了NATALEE研究[7]根据绝经状态和年龄的IDFS分析。结果显示，绝经前（HR 0.671）和绝经后（HR 0.746）患者均有一致的IDFS获益，在年轻（＜40岁）和老年（＞60岁）乳腺癌患者中，4年IDFS也分别提高了6.3%（HR 0.690）和6.4%（HR 0.673）。CDK4/6i强化辅助治疗能否带来更加远期的治疗获益，需要未来持续的随访分析。△NATALEE研究：按绝经状态和年龄的IDFS分析在CDK4/6i辅助治疗中，合适的剂量和疗程也是临床讨论热点之一，monarchE研究中有CDK4/6i组有2.4%的停药率和61.7%的中断率[8]。这次ASCO大会报道的II期TRADE研究[9]，使用阿贝西利剂量递增的策略，能够使大多数（70.8%）患者在12周时达到维持150mg剂量，而且观察到腹泻等不良反应的减少。这种治疗模式为未来CDK4/6i辅助治疗提供了有益的参考。HER2+ eBC新辅助精准治疗助推“降阶梯”治疗理念《肿瘤瞭望》：最后能否分享一下HER2阳性早期乳腺癌领域的ASCO重要研究进展？邵志敏 教授复旦大学附属肿瘤医院在HER2阳性早期乳腺癌领域，总体上“降阶梯”的研究和讨论较为受关注。广东省人民医院王坤教授报告的neoCARHP研究[10]，首次在III期随机对照试验中比较了THP和TCbHP新辅助治疗，结果显示二者的完全病理缓解（pCR）率达到了非劣效性（64.1% vs 65.9%；绝对差异 -1.8%，95%CI：-8.5~5.0；非劣效界值 -10%），但THP组的3-4级不良事件（20.7% vs 34.6%）、严重不良事件（1.3% vs 4.7%）均低于TCbHP组；其中，3-4级的中性粒细胞减少（6.8% vs 16.4%）、白细胞减少（5.5% vs 14.8%）、腹泻（2.6% vs 4.2%）发生率都有较大幅度的降低。该研究结果表明，THP方案具有不劣于TCbHP的pCR率和更好的治疗耐受性，“去卡铂”双靶治疗方案可作为HER2阳性早期乳腺癌新辅助治疗的降阶梯策略。△neoCARHP研究:两组的pCR率和安全性（左右滑动查看）另一项针对西德研究协作组（WSG）三项研究的汇总分析[12]，则探讨减少或豁免化疗的12周新辅助治疗策略，结果显示有或无化疗的5年OS率没有差异（98% vs 97%，HR 0.88，P=0.775），达到pCR的患者5年IDFS率都很高（98% vs 94%，HR 0.76；P=0.609），这些结果为HER2+早期乳腺癌的降阶梯治疗带来新的参考，某些特定患者的双靶新辅助治疗可以“去化疗”。此外，EA1181/CompassHER2 pCR研究[11]，使用了HER2DX pCR评分来预测THP新辅助治疗的pCR，结果显示二者显著相关，这将有助于更加精准筛选THP新辅助治疗患者。目前，我们团队已经针对HER2阳性乳腺癌提出了“复旦分型”，包括对抗HER2治疗效果更好的经典HER2亚型（HER2-CLA），以免疫激活微环境为特征的免疫调节亚型（HER2-IM），对内分泌治疗和CDK4/6i敏感的管腔样亚型（HER2-LUM），以RTK信号通路激活为特征的基底/间充质样亚型（HER2-BM）。这些分子分型在早期HER2阳性乳腺癌精准治疗中的应用有待进一步验证。参考文献上下滑动查看更多内容[1]Yu KD, Ye FG, He M, et al. Effect of Adjuvant Paclitaxel and Carboplatin on Survival in Women With Triple-Negative Breast Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020;6(9):1390-1396. doi:10.1001/jamaoncol.2020.2965[2]Vicente Valero, et al.NRG-BR003: A randomized phase III trial comparing doxorubicin plus cyclophosphamide followed by weekly paclitaxel with or without carboplatin for node-positive or high-risk node-negative TNBC.ASCO 2025;Abstract #LBA509[3]Christian F. Singer,et al.Prospective randomized phase II trial to assess the efficacy and safety of neo-adjuvant olaparib/carboplatin (OC) in comparison to docetaxel/epirubicin/cyclophosphamide (TAC) in patients with early triple-negative breast cancer (TNBC) with homologous recombination deficiency (HRD): Primary results from the ABCSG 45 trial.ASCO 2025;Abstract #510[4]Rachel Abelman, et al.A phase 2 study of response-guided neoadjuvant sacituzumab govitecan and pembrolizumab (SG/P) in patients with early-stage triple-negative breast cancer: Results from the NeoSTAR trial.ASCO 2025;Abstract #511[5]Zhimin Shao,et al.Dalpiciclib (Dalp) plus endocrine therapy (ET) as adjuvant treatment for HR+/HER2– early breast cancer (BC): The randomized, phase 3, DAWNA-A trial.ASCO 2025;Abstract #515[6]Prudence Francis,et al.15-year outcomes for women with premenopausal hormone receptor-positive early breast cancer (BC) in the SOFT and TEXT trials assessing benefits from adjuvant exemestane (E) + ovarian function suppression (OFS) or tamoxifen (T)+OFS.ASCO 2025;Abstract #505[7]Kevin Kalinsky, et al.Efficacy and safety of ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) in NATALEE: Analysis across menopausal status and age..ASCO 2025;Abstract #516[8]Johnston SRD, Toi M, O'Shaughnessy J, et al. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023;24(1):77-90. doi:10.1016/S1470-2045(22)00694-5[9]Erica Mayer, et al.The TRADE study: A phase 2 trial to assess the tolerability of abemaciclib dose escalation in early-stage HR+/HER2- breast cancer.ASCO 2025;Abstract #517[10]Kun Wang,et al.De-escalated neoadjuvant taxane plus trastuzumab and pertuzumab with or without carboplatin in HER2-positive early breast cancer (neoCARHP): A multicentre, open-label, randomised, phase 3 trial.ASCO 2025;Abstract #LBA500[11]Monika Karla Graeser, et al.Prediction of survival after de-escalated neoadjuvant therapy in HER2+ early breast cancer: A pooled analysis of three WSG trials.ASCO 2025;Abstract #502[12]Nadine Tung,et al.Predicting pathologic complete response (pCR) from clinicopathologic variables and HER2DX genomic test in stage II/III HER2+ breast cancer treated with taxane, trastuzumab, and pertuzumab (THP): Secondary results from the EA1181/CompassHER2 pCR trial.ASCO 2025;Abstract #501[13]Li YW, Dai LJ, Wu XR, et al. Molecular Characterization and Classification of HER2-Positive Breast Cancer Inform Tailored Therapeutic Strategies. Cancer Res. 2024 Aug 26. 邵志敏 教授复旦大学附属肿瘤医院乳腺肿瘤多学科团队首席专家首批教育部“长江学者奖励计划”特聘教授国家杰出青年科学基金获得者复旦大学特聘教授现任复旦大学肿瘤研究所所长、乳腺癌研究所所长，复旦大学附属肿瘤医院大外科主任兼乳腺外科主任中国抗癌协会乳腺癌专业委员会名誉主任委员中国抗癌协会肿瘤靶向治疗专业委员会主任委员中国临床肿瘤学会（CSCO）理事中国医师协会临床精准医疗专业委员会乳腺癌学组主任委员上海市抗癌协会副理事长上海市医学会肿瘤专科分会名誉主任委员第八届亚洲乳腺癌协会主席《中国癌症杂志》主编St.Gallen国际乳腺癌大会专家团成员（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。