Letrozole

近年来，乳腺癌诊疗领域取得了诸多突破性进展，特别是在靶向治疗、个体化策略及药物研发等方面。其中，复宏汉霖自主研发并生产的首个中国籍曲妥珠单抗作为国产生物药的代表，凭借高品质、可负担的治疗优势，为广大乳腺癌患者提供了优质的治疗选择。这不仅彰显了中国生物药研发能力的崛起，也为乳腺癌诊疗的高质量发展注入了强劲动力。基于此，医脉通特别邀请中国医学科学院肿瘤医院徐兵河教授作为开场嘉宾，河北医科大学第四医院耿翠芝教授、中山大学孙逸仙纪念医院刘强教授以及哈尔滨医科大学附属肿瘤医院张清媛教授作为访谈嘉宾，共同分享近年来乳腺癌诊疗领域的突破性进展，深入解析国产生物药在临床实践中的应用感受，并展望其未来在乳腺癌诊疗领域的广阔前景。开场致辞徐兵河 教授过去几十年，乳腺癌研究和治疗取得了显著进展。我们见证了分子生物学的发展，使我们能够更加深入了解乳腺癌的发病机制；靶向治疗和免疫疗法的兴起，为患者提供了更加精准和有效的治疗方案；乳腺癌筛查和早期诊断技术的改进，使得更多的患者能够在疾病早期得到治疗，极大地提高了患者生存率。这些成就离不开全球、包括我国无数科研人员、临床医生和医药企业的共同努力。我国近年来在乳腺癌药物治疗领域也取得了很多进展，从化学仿制药到大分子生物类似药，再到各种创新药物，这也是“中国方案”能在国际上获得认可，改写乳腺癌治疗格局的前提条件。我也非常有幸主导了国内首个曲妥珠单抗生物类似药的注册临床研究，这也是乳腺肿瘤领域第一个由中国专家领导的国际多中心研究1。通过这一重要研究，使得首个国产曲妥珠单抗生物类似药在中、美、欧等50多个国家和地区获批上市。我觉得该药物成功的意义不仅仅是已经治疗了超过24万的国内外患者，而且还有以下几点意义：首先是我们中国专家有能力主导全球性产品的临床研究，之前国内市场上见到的全球上市的药物都是国外专家作为主要研究者，中国是分中心参与。其次是这项临床研究的成功，标志着中国药企生产的药品在产品质量上被国际认可，印证了中国生物制药企业的实力在这些年中有长足的进步。还有非常重要的一点是，它拉开了国内生物类似药研究的序幕，到今天为止，我们已经有5个国产曲妥珠单抗获批，两个国产帕妥珠单抗获批，而曲妥珠单抗、帕妥珠单抗是HER2+乳腺癌的重要治疗药物。某种程度上，这些基本治疗药物的国产化也为广大患者的药物供给提供了有效的保障。虽然在过去二十年中，我国乳腺癌诊疗取得了长足进步，但仍面临诸多挑战。我相信，在科研人员、临床医生和医药企业的共同努力下，中国的乳腺癌研究将不断实现新突破，将会有越来越多的乳腺癌新产品上市，为乳腺癌患者带来更多希望，不断提高乳腺癌患者的生存率。耿翠芝 教授近年来，随着乳腺癌发病率逐年上升且呈现年轻化趋势，患者的治疗需求也在发生变化，不仅追求长期生存，更注重生活质量的改善。针对这一趋势，乳腺癌的治疗手段也随之不断优化和改进。在外科治疗方面，乳腺癌手术方式已从传统的乳房全切及腋窝淋巴结清扫，逐渐转向保乳手术、乳房切除后的重建手术以及腋窝前哨淋巴结活检。若前哨淋巴结活检结果为阳性，则可能需要进行腋窝淋巴结清扫。然而，随着放疗技术的提升，依据Z0011及AMAROS等多项研究2-3结果，对于保乳手术联合前哨淋巴结活检的患者，即使腋窝淋巴结有1-2个出现阳性，也可采用放疗替代清扫。此外，INSEMA研究4指出，部分高龄且低风险（如G1）的HR+乳腺癌患者，或许可以避免前哨淋巴结活检。与此同时，随着人工智能技术的进步和手术技术的精准化提升，微创手术如机器人辅助手术和腔镜手术等迅速应用于临床，为乳腺癌的外科治疗带来了革命性的突破。在药物治疗领域，随着对分子分型的深入研究，乳腺癌的治疗策略更加精准。对于三阴性乳腺癌，免疫治疗的引入改善了患者的预后。对于HR+乳腺癌，CDK4/6抑制剂的应用显著延长了患者的无进展生存期（PFS）和总生存期（OS）。此外，HER2+乳腺癌的治疗手段层出不穷，包括大分子抗HER2药物、小分子酪氨酸激酶抑制剂（TKI）以及HER2抗体药物偶联物（ADC）的不断涌现，极大地丰富了治疗选择，为患者提供了更多治疗机会和生存希望。刘强 教授在过去十几年间，中国乳腺癌诊疗领域取得了翻天覆地的变化。这一方面得益于生活水平的快速提高，人们对生活质量和优质医疗方案的需求显著增长；另一方面，也与乳腺癌本身作为全球发病率最高的肿瘤之一，中国患病人数迅速增加的背景密切相关。据统计，过去20年，中国乳腺癌患者数量几乎翻了一倍。2011年底回国至今，我亲眼见证了中国乳腺专科的快速发展过程。当时，全国很多医院尚未设立乳腺专科，包括许多大型医院，多采用普外科或者甲乳外科的模式。然而，乳腺癌的治疗并非仅依赖外科模式，其治愈效果一半归功于外科手术，另一半则依赖于强大的精准系统治疗。因此，乳腺专科的建设逐渐得到高度重视，越来越多的医院开始设立乳腺专科，为患者提供更专业、更系统的诊疗服务。十年前，中国在乳腺癌诊疗领域与欧美国家存在较大差距，主要体现在以下两个方面：首先，在手术方面，当时中国乳腺癌患者接受保乳手术的比例相对较低，即便是一些大医院。而如今，随着医疗技术的进步和治疗理念的革新，中国乳腺癌保乳手术的比例大幅提高。其次，是药物可及性问题。当年刚回国时，HER2+乳腺癌唯一的靶向药物曲妥珠单抗在中国的使用率较低，因为当时该药物全自费，一年费用高达三四十万，对绝大多数中国家庭来说难以承受。后来，随着药物价格的降低以及进入医保，情况逐渐改善。如今，中国患者在靶向治疗方面的应用甚至比国外还要好，这主要得益于中国医保的覆盖以及国产生物药的上市，其产生的竞争导致药物价格明显下降，进一步推动了药物普及性的提高。目前，中国在乳腺癌治疗药物方面已与国际相差无几，甚至在某些方面更具优势。我们拥有更多自己研发的物美价廉的药物，例如CDK4/6抑制剂、曲妥珠单抗、帕妥珠单抗等药物的价格仅为欧美的1/10甚至更低。随着诸多本土企业生物药的上市，极大地推动了市场竞争和药物普及，充分体现了中国在生物医药方面自给自足的能力。此外，中国现在也有越来越多的创新药在全球引领风骚。去年，中国药物在全球创新药成交额中占比超过30%，这一成绩在过去是难以想象的。中国生物制药企业的竞争力显著增强，也带动了中国医学整体的进步以及患者诊治水平的显著提高。可以说，乳腺癌诊疗领域的发展，已成为中国高端制造产业的一个缩影，标志着中国不仅在传统制造业如服装、鞋类等领域有优势，如今在生物制药等高端制造业也占据了一席之地。当然，这离不开众多优秀民族药企的投入和研发，以及与医疗机构的密切合作。Q2：在过去二十年乳腺癌诊疗飞速发展的历程中，国产生物药的崛起，尤其是曲妥珠单抗生物类似药的问世，无疑为HER2+乳腺癌治疗带来了新的曙光。请您谈谈国产生物药的上市，对于改善HER2+乳腺癌患者的治疗现状，以及推动我国生物药规范化进程的发展具有哪些重要意义?耿翠芝 教授在HER2+乳腺癌治疗领域，生物类似药的引入为患者带来了显著的益处。国产大分子生物类似药在前期研究中均经过严格的一致性评价，其疗效与原研药相当。例如，首个国产曲妥珠单抗生物类似药以及今年进入临床的帕妥珠单抗生物类似药，在临床研究中均展现出与原研药相似的疗效。这不仅为患者提供了更多选择，还显著降低了治疗成本，尤其是这些国产生物药进入医保后，极大地减轻了患者的经济负担，使更多患者能够受益于精准治疗。此外，国产生物药的应用，有效缓解了进口药物在临床使用中可能面临的供应压力。近年来，随着乳腺癌患者数量的持续增加，以及国际环境和贸易政策的不确定性，进口药物在供应链、准入政策以及成本上的问题逐渐显现。例如，在疫情期间，药品进口受限，导致部分患者无法及时获得有效治疗。此外，贸易政策的不确定性，如关税调整和市场准入限制，也可能影响进口药的供应。而国产生物药依托国内完善的生产与供应链体系，能够有效抵御国际贸易政策波动带来的风险，避免出现类似进口药的断供问题，为患者提供了坚实的治疗保障。国产生物药不仅确保了患者的治疗效果，更实现了从“人适合药”到“药适合人”的跨越，也在一定程度上保障了医疗资源的公平分配，促使各级医疗机构更广泛地采用标准化的抗HER2治疗方案，减少了城乡之间的医疗差距，加速推动我国乳腺癌诊疗规范化的进程。Q3：我们知道您是首个国产曲妥珠单抗III期研究的重要参与者，在该药物上市之初您就已积累了丰富临床经验。在您看来，该药物有哪些比较好的特点或优势？张清媛 教授我们知道，临床中曲妥珠单抗的应用是按照患者体重计算的，不管是采取一周治疗方案（起始剂量为4mg/kg，维持剂量为2mg/kg）还是三周治疗方案（起始剂量为8mg/kg，维持剂量为6mg/kg）给药，使用440mg规格的原研曲妥珠单抗，一般一支用不完，所以会存在弃液浪费、多次使用等问题。为了使剩余的药液下次继续使用，原研药通过额外添加苯甲醇作为防腐剂。不过，防腐剂可能会引发一定的副作用，而且余液保存也给患者和医院管理带来了额外的挑战。而国产曲妥珠单抗临床研究1中使用的药物规格是150mg，采用即配即用模式，可以有效解决弃液浪费、余液保存的问题。这不仅减少了余液保存可能带来的隐患，还显著提高了药学部门以及护理部门的工作效率，同时也为更多患者节省了医疗费用。此外，由于不含防腐剂，该药物进一步降低了因防腐剂可能引发的副作用风险，为患者用药的安全性和便捷性提供了有力保障。在临床实践中，我们对国产曲妥珠单抗的应用更加充满信心。这一信心不仅源于我们中心积极参与了该药物的国际III期临床研究1，纳入了大量患者，在研究过程中也看到，该药物在疗效和安全性方面与原研药一致，表现令人非常满意和放心。而且，这款国产曲妥珠单抗生物类似药在通过国内严格审批的同时，还成功获得欧盟的上市批准，成为我国首款“出海”的曲妥珠单抗生物类似药。这一成就进一步证明了其优异的国际品质，为我们在临床中的使用提供了更大的信心保障。Q4：基于III期临床研究中卓越的疗效，首个国产曲妥珠单抗生物类似药（150mg规格）先后在欧盟和中国获批上市。然而，上市之后该药物的探索并未止步。在过去五年中，您最关注该药物在哪些方面的持续研究与进展？张清媛 教授该药物在为中国和欧洲乳腺癌患者提供可负担的治疗选择后，继续致力于为其他国家和地区的患者带来福音。截至目前，该药物已在全球50多个国家和地区获批上市，并成功纳入中、英、法、德等多个国家的医保目录，造福全球患者。国产生物药在国际上的广泛应用，不仅体现了其卓越的疗效和安全性，也彰显了中国在药物研发与制造领域的强大实力。这不仅令人高兴，更让人振奋，让我们看到了国产生物药在全球范围内获得高度认可，取得了令人瞩目的地位。同时，国产生物药也有效减轻了患者的经济负担以及各国医保系统的压力。更重要的是，它为更多HER2+乳腺癌患者提供了有力的武器，帮助他们战胜疾病，重获健康。刘强 教授生物类似药属于大分子药物，其研发和生产曾被认为是一个巨大的挑战。与普通化合物药物的仿制相比，大分子生物类似药的研发更为复杂，难度犹如制造单车与飞机的差异。尽管我们在普通化合物的仿制上已取得一定经验，但对于大分子生物类似药的研发能力，过去仍存在一定的质疑。然而，首个国产曲妥珠单抗生物类似药的成功上市，为这一领域带来了突破。其临床研究数据表现优异，不过临床研究的受试人群相对有限，为了更全面地评估药物在实际应用中的有效性和安全性，该药物在上市后仍持续开展了多项真实世界研究，例如复旦大学附属肿瘤医院、南京鼓楼医院、牡丹江市肿瘤医院进行的回顾性研究5-6均表明，国产双规格曲妥珠单抗与原研药具有相似的真实世界疗效和安全性。这些研究结果与我们临床实际应用中的观察高度一致，进一步增强了我们对该药物应用的信心，也为国产大分子生物类似药的研发和应用提供了有力的证据支持。正如中国自主研发的C919飞机成功升空并赢得国际认可一样，国产生物类似药也在不断向全球证明中国在高技术领域的研发实力和创新能力。Q5：随着乳腺癌治疗领域的不断发展，您如何看待曲妥珠单抗等国产生物药在当前乳腺癌治疗中地位和未来发展潜力？张清媛 教授对于HER2+乳腺癌，抗HER2治疗是核心治疗策略。曲妥珠单抗作为首个抗HER2单克隆抗体药物，具有极为重要的临床地位。其不仅可以与大分子抗体药物如帕妥珠单抗联合使用，还可与小分子TKI类药物如吡咯替尼联用。此外，临床研究还在不断探索曲妥珠单抗与免疫治疗药物的联合应用7等。无论是在新辅助治疗、辅助治疗还是晚期治疗中，曲妥珠单抗均发挥着不可或缺的作用。如今，我们有了中国自主研发的曲妥珠单抗生物类似药，其疗效可靠且安全性良好，已在全球多个国家获批上市，显著提升了抗HER2治疗的可及性，使更多患者能够以更经济的方式获得高质量的治疗，具有重要的临床和社会意义。刘强 教授近年来，中国在国产生物药领域的发展势头迅猛，不仅成功推出了曲妥珠单抗生物类似药、帕妥珠单抗生物类似药，还在新型ADC等方面取得了显著进展。中国拥有全球最多的乳腺癌患者人群，这一事实决定了我们必须拥有自主研发的药物，以更好地保障中国患者的治疗安全和药物可及性。尤其是在全球贸易格局可能发生变化的背景下，药物的自主研发显得尤为重要。生物药的研发并非易事，其市场容量有限，正如不可能存在百家飞机制造公司一样，只有具备强大研发能力和质量保障的企业才能脱颖而出。我们希望中国药企在市场竞争中，不仅要注重价格优势，更要将质量放在首位。只有这样，中国生物制药行业才能在国内取得长足发展，并进一步走向国际舞台。目前，中国许多药物已凭借其高性价比成为全球市场的优质选择。中国药企走向世界并非为了与他国恶性竞争，而是通过优质药物为全球患者造福。相信未来，中国的生物制药产业将在国际市场中占据重要地位，为全球医疗事业的发展贡献更多力量。耿翠芝 教授最近，在国际医学领域的重要会议，如SABCS会议、SGBCC会议、ASCO会议以及ESMO会议中，中国研究和国产生物药的影响力日益凸显，逐渐登上国际舞台并占据重要地位。今年SGBCC会议更是特别设立了“中国专场”，吸引了众多国际知名专家的参与。在该专场中，中国专家分享了国产生物药的卓越疗效数据，以及由中国学者牵头开展的临床研究成果。例如，三阴性乳腺癌“复旦四分型”针对中国患者的特征，提供了更加精准的治疗指导。此外，徐教授、邵教授、江教授等专家领导的多项中国临床研究，如DAWNA-1研究8、DAWNA-2研究9、PHILA研究10、FUTURE-C-plus研究11以及TORCHLIGHT研究12等，均获得了国际专家的高度认可。这些研究纳入的均为中国患者，因此其对于指导中国乳腺癌患者的治疗具有极高的参考价值。这些数据和研究结果的亮相，不仅展现了中国药物研发的快速发展，也进一步巩固了中国在国际肿瘤学领域的学术地位。尽管目前的研究数据主要基于中国人群，但随着国产生物药在国际市场上的布局不断拓展，未来中国优质药物必将走向世界，为全球患者带来更多的治疗选择和希望。总结截至当下，首个国产曲妥珠单抗生物类似药已上市近五载。凭借卓越的品质和高度的可及性，该药物为广大乳腺癌患者带来了新的希望，显著改善了患者的治疗现状。这不仅是国产生物药研发能力崛起的有力证明，更是中国医药行业在国际舞台上崭露头角的重要标志。未来，随着更多创新药物的研发和临床应用，国产生物药有望在全球范围内发挥更大作用，为全球患者提供更多优质可及的治疗选择，为人类健康事业贡献更多“中国力量”。（点击观看完整视频）参考文献1. Xu B, Zhang Q, Sun T, et al. Efficacy, Safety, and Immunogenicity of HLX02 Compared with Reference Trastuzumab in Patients with Recurrent or Metastatic HER2-Positive Breast Cancer: A Randomized Phase III Equivalence Trial. BioDrugs. 2021 May;35(3):337-350.2. Jagsi R, Chadha M, Moni J, et al. Radiation field design in the ACOSOG Z0011 (Alliance) Trial. J Clin Oncol. 2014;32(32):3600-3606.3. Bartels SAL, Donker M, Poncet C, Sauvé N, et al. Radiotherapy or Surgery of the Axilla After a Positive Sentinel Node in Breast Cancer: 10-Year Results of the Randomized Controlled EORTC 10981-22023 AMAROS Trial. J Clin Oncol. 2023 Apr 20;41(12):2159-2165.4. Reimer T, Stachs A, Veselinovic K, et al. Axillary Surgery in Breast Cancer - Primary Results of the INSEMA Trial. N Engl J Med. 2025 Mar 13;392(11):1051-1064.5. Zhi-Ming Shao, et al.Trastuzumab(HLX02)plus Pertuzumab as Dual-target Neoadjuvant Therapy for HER2-positive Breast Cancer:A Real-World Study. SABCS 2022. Abstract P1-11-20.6. Liu Z, Guan Y, Yao Y, et al. Effectiveness and Safety of Zercepac and Reference Trastuzumab in the Neoadjuvant Setting for Early-Stage Breast Cancer: A Retrospective Cohort Study. J Oncol. 2022 Nov 3;2022:9998114.7. Loi S, Giobbie-Hurder A, Gombos A, et al. Pembrolizumab plus trastuzumab in trastuzumab-resistant, advanced, HER2-positive breast cancer (PANACEA): a single-arm, multicentre, phase 1b–2 trial. Lancet Oncol. 2019;20(3):371–82.8. Xu B, et al. DAWNA-1 Study Consortium. Dalpiciclib or placebo plus fulvestrant in hormone receptor-positive and HER2-negative advanced breast cancer: a randomized, phase 3 trial. Nat Med. 2021 Nov;27(11):1904-1909.9. Zhang P, et al. Dalpiciclib plus letrozole or anastrozole versus placebo plus letrozole or anastrozole as first-line treatment in patients with hormone receptor-positive, HER2-negative advanced breast cancer (DAWNA-2): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. Published online May 11, 2023.10. Ma F, Yan M, Li W, et al. Pyrotinib versus placebo in combination with trastuzumab and docetaxel as first line treatment in patients with HER2 positive metastatic breast cancer (PHILA): randomised, double blind, multicentre, phase 3 trial. BMJ. 2023 Oct 31;383:e076065.11. Chen L, Jiang YZ, Wu SY, et al. Famitinib with Camrelizumab and Nab-Paclitaxel for Advanced Immunomodulatory Triple-Negative Breast Cancer (FUTURE-C-Plus): An Open-Label, Single-Arm, Phase II Trial. Clin Cancer Res. 2022;28(13):2807-2817.12. Jiang Z, Ouyang Q, Sun T, et al. Toripalimab plus nab-paclitaxel in metastatic or recurrent triple-negative breast cancer: a randomized phase 3 trial. Nat Med. 2024 Jan;30(1):249-256.专家简介徐兵河 教授中国工程院院士中国医学科学院学部委员北京协和医学院长聘教授国家抗肿瘤新药临床研究中心主任中国抗癌协会乳腺癌专业委员会和肿瘤药物临床研究专业委员会名誉主任委员北京肿瘤学会和北京乳腺病防治学会理事长耿翠芝 教授二级教授 博士研究生导师河北医科大学第四医院乳腺中心中国抗癌协会理事中国临床肿瘤学会理事中国临床肿瘤学会乳腺癌专家委员会副主任委员中国女医师协会临床肿瘤分会副主任委员河北省抗癌协会乳腺癌专业委员会主任委员刘强 教授主任医师 教授 研究员 博士生导师中山大学孙逸仙纪念医院外科主任逸仙乳腺肿瘤医院执行副院长 中山大学孙逸仙纪念医院乳腺肿瘤中心主任 乳腺外科主任ESO-ESMO年轻乳腺癌国际共识专家组成员中国临床肿瘤学会乳腺癌专业委员会常务委员兼副秘书长中国抗癌协会乳腺癌专业委员会常务委员中国抗癌协会肿瘤分子医学专业委员会常务委员广东省医学会乳腺病分会主任委员广东省抗癌协会乳腺癌专业委员会主任委员中国普通外科杂志副主编和中华内分泌外科杂志副总编辑新加坡国立大学外科博士 回国前任哈佛大学Dana Farber癌症中心讲师张清媛 教授主任医师 二级教授 博士生导师肿瘤学国家重点专科带头人国家百千万人才工程入选者国家突出贡献中青年专家中国抗癌协会乳腺癌专业委员会副主任委员中国临床肿瘤学会乳腺癌专家委员会副主任委员中国抗癌协会化疗专业委员会副主任委员撰写：Max审校：Max排版：米子执行：Atai本平台旨在为医疗卫生专业人士传递更多医学信息。本平台发布的内容，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。如该等信息被用于了解医学信息以外的目的，本平台不承担相关责任。本平台对发布的内容，并不代表同意其描述和观点。若涉及版权问题，烦请权利人与我们联系，我们将尽快处理。

Positive recommendation based on phase III INAVO120 data showing ItovebiTM (inavolisib) in combination with palbociclib and fulvestrant more than doubled progression-free survival in the first-line setting1 The Itovebi-based regimen also demonstrated a statistically significant and clinically meaningful benefit in overall survival (OS) in the final OS analysis Final OS data will be presented in an oral session at the 2025 American Society of Clinical Oncology Annual Meeting 23 May 2025 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion for Itovebi™ (inavolisib), in combination with palbociclib (Ibrance®) and fulvestrant, for the treatment of adult patients with PIK3CA-mutated, oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer, following recurrence on or within 12 months of completing adjuvant endocrine treatment. If approved, the Itovebi-based regimen has the potential to transform the standard of care in this first-line setting, where treatments are currently limited.1 A final decision regarding the approval is expected from the European Commission in the near future. “The positive CHMP recommendation for the Itovebi-based regimen represents a significant step towards providing people in the EU with PIK3CA-mutated, ER-positive advanced breast cancer with a targeted therapy in the first-line setting,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “This recommendation is further enforced by the recent final overall survival results from the INAVO120 study, showing the regimen can meaningfully extend survival.” The presence of a PIK3CA mutation, found in approximately 40% of hormone receptor (HR)-positive breast cancers, can make the disease more aggressive and worsen survival outcomes.2,3 This underscores the importance of testing for PIK3CA mutations prior to first-line treatment so that people with a poor prognosis can benefit from an effective, PI3K-targeted therapy as soon as possible. The CHMP’s positive opinion is based on the phase III INAVO120 results, published in the New England Journal of Medicine in October 2024, which showed a 57% reduction in the risk of disease worsening or death (progression-free survival [PFS]) with the Itovebi-based regimen compared with palbociclib and fulvestrant alone (15.0 months vs. 7.3 months; hazard ratio [HR]=0.43, 95% CI: 0.32-0.59, p1 The PFS benefit was consistent across all pre-specified subgroups, including people whose disease had spread to three or more locations, characterised as difficult-to-treat disease.1 The Itovebi-based regimen was well tolerated, with no new safety signals observed.1 Positive topline results from the final overall survival (OS) analysis, announced in January 2025, showed a statistically significant and clinically meaningful OS benefit with the Itovebi-based regimen. OS data were immature at the time of primary analysis, but a clear positive trend was observed (stratified HR=0.64, 95% CI: 0.43-0.97, p=0.0338 (boundary of 0.0098)).1 The full results from the OS analysis will be presented in an oral session at the 2025 American Society of Clinical Oncology Annual Meeting. The Itovebi-based regimen is approved for the treatment of adults with endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer in the United States, Switzerland, Canada, Australia, United Arab Emirates and China, with data from INAVO120 under review with other global health authorities. Beyond INAVO120, Itovebi is currently being investigated in three company-sponsored phase III studies (INAVO121, INAVO122, INAVO123), all in PIK3CA-mutated, locally advanced or metastatic breast cancer in various combinations.4-7 We are exploring additional studies in breast cancer and other tumour types with the hope of providing the benefit of this targeted therapy to more people with PIK3CA mutations. Itovebi is an oral, targeted treatment that has been shown to provide well-tolerated and durable disease control in people with advanced PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, who often have a poor prognosis and are in urgent need of new treatment options.1-3 Itovebi has been designed to help minimise the overall burden and toxicity of treatment and is differentiated from other PI3K inhibitors due to its high potency and specificity for the PI3K alpha isoform versus other isoforms, and unique mechanism of action that facilitates the degradation of mutated PI3K alpha.8,9 The INAVO120 study [NCT04191499] is a phase III, randomised, double-blind, placebo-controlled study evaluating the efficacy and safety of Itovebi™ (inavolisib) in combination with palbociclib and fulvestrant versus placebo plus palbociclib and fulvestrant in people with PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer whose disease progressed during treatment or within 12 months of completing adjuvant endocrine therapy and who have not received prior systemic therapy for metastatic disease.4 The study included 325 patients, who were randomly assigned to either the investigational or control treatment arm.4 The primary endpoint is progression-free survival, as assessed by investigators, defined as the time from randomisation in the clinical trial to the time when the disease progresses, or a patient dies from any cause.4 Secondary endpoints include overall survival, objective response rate, and clinical benefit rate.4 Beyond INAVO120, Itovebi is currently being investigated in three additional company-sponsored phase III clinical studies in PIK3CA-mutated, locally advanced or metastatic breast cancer in various combinations:5-7 in combination with fulvestrant versus alpelisib plus fulvestrant in HR-positive/HER2-negative breast cancer post cyclin-dependent kinase 4/6 (CDK4/6) inhibitor and endocrine combination therapy (INAVO121; NCT05646862). in combination with pertuzumab plus trastuzumab for subcutaneous injection (SC) versus pertuzumab plus trastuzumab for SC and optional physician's choice of endocrine therapy as a maintenance treatment in HER2-positive disease (INAVO122; NCT05894239). in combination with a CDK4/6 inhibitor and letrozole versus placebo plus a CDK4/6 inhibitor and letrozole in the first-line setting in PIK3CA-mutated HR-positive/HER2-negative, endocrine-sensitive breast cancer (INAVO123; NCT06790693). HR-positive breast cancer is the most prevalent type of all breast cancers, accounting for approximately 70% of cases.10,11 A defining feature of HR-positive breast cancer is that its tumour cells have receptors that attach to one or both hormones – oestrogen or progesterone – which can contribute to tumour growth. People diagnosed with HR-positive metastatic breast cancer often face the risk of disease progression and treatment side effects, creating a need for additional treatment options.11-13 The PI3K signalling pathway is commonly dysregulated in HR-positive breast cancer, often due to activating PIK3CA mutations, which have been identified as a potential mechanism of intrinsic resistance to standard of care endocrine therapy in combination with cyclin-dependent kinase 4/6 inhibitors.3 Roche has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with companion diagnostic tests, have contributed to bringing breakthrough outcomes in human epidermal growth factor 2-positive and triple-negative breast cancers. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for other subtypes of the disease, including oestrogen receptor-positive breast cancer, which is a form of hormone receptor-positive breast cancer, the most prevalent type of all breast cancers.10,11 Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. For over 125 years, sustainability has been an integral part of Roche’s business. As a science-driven company, our greatest contribution to society is developing innovative medicines and diagnostics that help people live healthier lives. Roche is committed to the Science Based Targets initiative and the Sustainable Markets Initiative to achieve net zero by 2045. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. References [1] Turner NC, et al. Inavolisib-Based Therapy in PIK3CA-Mutated Advanced Breast Cancer. NEJM. 2024;391(17):1584-96. [2] Fillbrunn M, et al. PIK3CA mutation status, progression and survival in advanced HR+/HER2- breast cancer: a meta-analysis of published clinical trials. BMC Cancer. 2022;22:1002. [3] Anderson E, et al. A Systematic Review of the Prevalence and Diagnostic Workup of PIK3CA Mutations in HR+/HER2– Metastatic Breast Cancer. Int J Breast Cancer. 2020;2020:3759179. [4] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Patients With PIK3CA-Mutant, Hormone Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic Breast Cancer (INAVO120) [Internet; cited 2025 May]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT04191499. [5] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy (INAVO121) [Internet; cited 2025 May]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05646862. [6] ClinicalTrials.gov. A Study to Evaluate the Efficacy and Safety of Inavolisib in Combination With Phesgo Versus Placebo in Combination With Phesgo in Participants With PIK3CA-Mutated HER2-Positive Locally Advanced or Metastatic Breast Cancer (INAVO122) [Internet; cited 2025 May]. Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05894239. [7] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety of Inavolisib Plus CDK4/​6 Inhibitor and Letrozole vs Placebo + CDK4/​6i and Letrozole in Participants With Endocrine-Sensitive PIK3CA-Mutated, Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer (INAVO123) [Internet; cited 2025 April]. Available from: https://clinicaltrials.gov/study/NCT06790693. [8] Juric D, et al. A phase I/Ib study of inavolisib (GDC-0077) in combination with fulvestrant in patients (pts) with PIK3CA-mutated hormone receptor-positive/HER2-negative (HR+/HER2–) metastatic breast cancer. Presented at San Antonio Breast Cancer Symposium, 2020 December 7-10; San Antonio, USA. Abstract #P5-17-05. [9] Hong R, et al. GDC-0077 is a selective PI3K alpha inhibitor that demonstrates robust efficacy in PIK3CA mutant breast cancer models as a single agent and in combination with standard of care therapies. Cancer Res. 2018;78(4):4-14. [10] National Cancer Institute: Surveillance, Epidemiology and Ends Result Program. Cancer Stat Facts: Female Breast Cancer Subtypes [Internet; cited 2025 April]. Available from: https://seer.cancer.gov/statfacts/html/breast-subtypes.html. [11] Lim E, et al. The natural history of hormone receptor-positive breast cancer. Oncology (Williston Park). 2012;26(8):688-94,696. [12] Tomas R and Barrios CH. Optimal management of hormone receptor positive metastatic breast cancer in 2016. Ther Adv Med Oncol. 2015;7(6):304-20. [13] Galipeau N, et al. Understanding key symptoms, side effects, and impacts of HR+/HER- advanced breast cancer: qualitative study findings. J Patient-Rep Outcomes. 2019;3(1):10. The content above comes from the network. if any infringement, please contact us to modify.