Fam-trastuzumab deruxtecan-NXKI

阿斯利康（AstraZeneca）近日宣布，DESTINY-Breast09 3期研究积极结果显示，作为HER2阳性转移性乳腺癌患者的一线治疗，德曲妥珠单抗联合帕妥珠单抗，与当前一线标准治疗方案THP（紫杉类药物联合曲妥珠单抗及帕妥珠单抗）相比，在无进展生存期（PFS）方面表现出高度统计学显著性和具有临床意义的改善。DESTINY-Breast09 3期研究成果在2025年美国临床肿瘤学会（ASCO）年会上以特别重磅研究摘要口头报告形式公布。德曲妥珠单抗是一种靶向 HER2 的抗体偶联药物（ADC），由第一三共和阿斯利康共同开发和商业化。基于DESTINY-Breast03试验结果，德曲妥珠单抗已在全球80多个国家获批，用于HER2阳性乳腺癌患者的二线治疗。在DESTINY-Breast09研究中，在预设的中期分析中，德曲妥珠单抗联合帕妥珠单抗与THP方案相比，可使疾病进展或死亡风险降低44%。经盲态独立中心评估（BICR），德曲妥珠单抗联合帕妥珠单抗组的PFS达到40.7个月，而THP组的PFS则为26.9个月。相较于THP组，德曲妥珠单抗联合帕妥珠单抗组的PFS获益在各个亚组中均保持一致，预设分层因素包括初诊或复发转移、激素受体状态以及 PIK3CA 突变状态。研究者评估的PFS显示，德曲妥珠单抗联合帕妥珠单抗组的中位PFS为40.7个月，显著优于THP组的20.7个月 。德曲妥珠单抗联合帕妥珠单抗组经确认的客观缓解率（ORR）为85.1%，而THP组为78.6%。德曲妥珠单抗联合帕妥珠单抗组有58例患者实现了完全缓解（CR），而THP组有33例。德曲妥珠单抗联合帕妥珠单抗组的中位缓解持续时间（DOR）超过三年（39.2个月），而THP组为26.4个月。在中期分析时，总生存期（OS）数据尚未成熟（数据截止时成熟度为16%），但中期OS数据显示，德曲妥珠单抗联合治疗方案相比THP方案呈现出获益的早期趋势。美国丹娜-法伯癌症研究所（Dana-Farber Cancer Institute）乳腺肿瘤科主任、医学博士、公共卫生硕士、该临床试验的主要研究者Sara Tolaney表示：“HER2阳性转移性乳腺癌患者往往会在接受一线标准治疗后、约两年内出现疾病进展。而DESTINY-Breast09 的研究结果显示，德曲妥珠单抗联合帕妥珠单抗治疗的中位无进展生存期超过三年，表明这一方案有望成为这类患者新的一线治疗标准。”阿斯利康全球执行副总裁，全球肿瘤研发负责人高书璨（Susan Galbraith）表示：“在HER2阳性转移性乳腺癌治疗的更早阶段使用德曲妥珠单抗，可能为患者带来重大治疗突破。DESTINY-Breast09试验表明，在一线治疗中，德曲妥珠单抗联合帕妥珠单抗相比标准治疗方案，显著延长了患者疾病进展前的生存时间，并使在影像学上无病灶迹象的患者数量提升近一倍。鉴于约三分之一患者在一线治疗进展后无法接受后续治疗，在确诊为转移性乳腺癌后尽早展开强效的治疗至关重要。"第一三共全球研发负责人Ken Takeshita博士表示：“德曲妥珠单抗正在持续重塑转移性乳腺癌的治疗格局。这是十多年来首次有新数据，在一线治疗中相较于THP方案，对HER2阳性乳腺癌广泛患者群体展现出更好疗效。DESTINY-Breast09研究表明，在确诊为转移性乳腺癌时即使用德曲妥珠单抗与帕妥珠单抗联合治疗，可以延缓疾病进展。” 新闻稿介绍，中位随访时间接近2.5年（29.2个月）。截至数据截止时，仍有302例（39.6%）患者在接受治疗，其中德曲妥珠单抗联合帕妥珠单抗组为174例，THP组为128例。在DESTINY-Breast09研究中，德曲妥珠单抗联合帕妥珠单抗的安全性特征与各单药已知的安全性特征一致，未发现新的安全性问题。经独立裁定委员会评估，接受德曲妥珠单抗联合帕妥珠单抗治疗的患者中，12.1%出现了间质性肺病 (ILD)/肺炎。大多数ILD事件为低级别（1级[n=17；4.5%]或2级[n=27；7.1%]），未报告出现3级或4级ILD事件。德曲妥珠单抗联合帕妥珠单抗组中有两例5 级（占 0.5%）ILD 事件。该研究另一项探索性治疗组——评估德曲妥珠单抗单药治疗与THP方案的对比——目前对患者和研究人员仍保持盲态，并将继续进行直至完成最终的PFS分析。参考资料：[1]DB09 III期试验：优赫得联合帕妥珠单抗一线治疗HER2阳性转移性乳腺癌，相较THP方案，可降低疾病进展或死亡风险44%. From https://mp.weixin.qq.com/s/Mge8R4Fptut5U6WA85629Q免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

New drugs, however heralded, take time to embed into clinical care.Enhertu, the powerful antibody-drug conjugate from Daiichi Sankyo and AstraZeneca, was first approved in the U.S. in 2019, before the world had even heard of a novel coronavirus. This past weekend, results presented at the American Society of Clinical Oncologys annual meeting showed its potential for use in the first-line treatment of metastatic breast cancer, the result of steady work by its makers to test it in earlier and more widely.Immunotherapies like Opdivo, Tecentriq and Imfinzi were first approved eight to 10 years ago. Now, after marching up through metastatic treatment of various tumors, data at ASCO demonstrated how they can be used more widely both before and after surgery in early cancer.And bispecific antibodies, a relatively recent addition to physicians treatment tool kit, are slowly being absorbed into practice, with some tinkering to manage their side effects. Likely a few of the experimental drugs featured over the past few days at ASCO, such as camizestrant or vepdegestrant, will go on to win approval in the years ahead.Gauging which of these data are truly practice-changing is best left for future meetings, but the BioPharma Dive team nonetheless has a few reflections after attending this years. Read on for three of our takeaways:Positive breast cancer data comes with caveatsThis year, ASCO was headlined by promising clinical trial results for several new breast cancer drugs.Enhertu could change the frontline standard of care for an aggressive kind of metastatic breast cancer. Vepdegestrant, an experimental targeted medicine, may help control tumor growth in a common type. And camizestrant, also from AstraZeneca, proved effective at sustaining the benefit patients with that more common tumor experience on first-line therapy.Across the board, we have practice changing data that were presented for every sub-type of breast cancer, which is really exciting said Nancy Chan, a medical oncologist specializing in breast cancer at the NYU Langone Perlmutter Cancer Center.There are important qualifications to the good news, however. Enhertu showed strong benefit as part of first-line treatment for metastatic tumors that are positive for a protein called HER2. But it comes with a dangerous side effect that may make doctors cautious about adoption if its approved in this setting. Moving Enhertu earlier also raises questions about what to use afterwards, since the ADC plays an important role in second-line treatment currently.Vepdegestant, a pill, has promise treating breast cancer patients whose tumors are estrogen receptor positive but lack the HER2 protein. Its efficacy over the common therapy fulvestrant was limited to only patients with mutations in a gene called ESR1, though; those patients without one didnt appear to benefit.A physician interviewed by Cantor Fitzgerald analyst Li Watsek's team was disappointed the drug “didn't show greater differentiation, Watsek wrote in a Monday note to clients.Adding camizestrant into clinical practice, meanwhile, will require greater adoption of a blood test used to monitor for those ESR1 mutations, which doctors fear may be costly and arduous.Still, the data presented should give doctors more options for controlling advanced breast cancer. And they may offer advantages important to patients, too. It's not a small change to remove the intramuscular injection of fulvestrant and change to oral,“ said Chan, about the vepdegestrant data. “That gives the patient back so much more control and significantly improves their quality of life.“ Ned Pagliarulo, Delilah AlvaradoBispecific drugs need troubleshootingIn just a few years, bispecific antibodies have gone from exciting innovation to a common part of clinical practice, used to treat not only late-stage blood cancers but also earlier-stage disease in some tumors. A whole cohort of new ones are in testing, making the field an active area of pharma dealmaking.But they carry immune-related side effects that were previously only seen with complex CAR-T cell therapies. Physicians must now also weigh those risks for a broader group of patients than before. Because theyre meant to be given as outpatient treatment CAR-Ts are often administered in a hospital some oncologists are cautious about using them, fearing patients may not be able to receive hospital care before the side effects they might experience cause serious illness or death.The specific conditions are known as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, both aggressive responses resulting from the activation of immune cells. In the case of Amgens newly launched lung cancer drug Imdelltra, a little more than half of study participants had CRS, usually after the first two doses. Around one in seven had ICANS, usually within the first 30 days, Abdul Rafeh Naqash, immuno-oncology director at the University of Oklahomas Stephenson Cancer Center, said in a panel discussion at ASCO, citing data from a pivotal trial.Melissa Johnson, director of lung cancer research at Sarah Cannon Research Institute, argues Imdelltra can be used outpatient by giving patients monitoring tools like thermometers, blood pressure cuffs and blood-oxygen monitors to detect side effects. The steroid dexamethasone could also be used to tamp down immune response. To reduce hospital stays with CAR-T patients, Sarah Cannon has tested wearable devices that provide continuous monitoring, Johnson said, which could be used for patients on bispecifics, too.There are more bispecifics coming in solid tumor oncology, she said. So we have to grapple with these things now so that we'll be able to give bispecifics for our prostate cancer patients and our breast cancer patients, where the CRS events may be more significant. Jonathan GardnerU.S. science cuts feed undercurrent of alarmASCOs hundreds of sessions were, by and large, concerned with the ins and outs of cancer study data and clinical practice. In that respect, this years meeting was much the same as it always is.But the Trump administrations aggressive downsizing of the federal health workforce and planned curtailment of science spending rippled through the meeting nonetheless.The White Houses budget calls for major reductions in funding for the National Institutes of Health and National Cancer Institute, which could imperil future cancer drug research. ASCO CEO Clifford Hudis used the meetings opening session to warn of the cuts likely impact.We find ourselves in a tragic paradox, he said on Friday. We are living in a time of unprecedented scientific opportunity, yet we are facing historic reductions in the very resources we need to turn these opportunities into hope for millions of patients counting on us.Chan, at the Perlmutter Cancer Center, told BioPharma Dive the effects are already becoming apparent. Across the board, we definitely are seeing a decrease in oncology funding for new ideas and new concepts, both at the clinical level and also at the translational basic sciences level, said Chan. I think that will have a long-term impact.Research that primarily looks at cancers affecting women, and related issues they may experience, could be most at stake. Trump has issued executive orders that target gendered language and DEI programs, potentially raising barriers for researchers seeking federal grant funding to study womens health.Regardless of where you are from in the world, breast cancer is the most common diagnosis in women for most countries, Chan said. This is a common issue for all of us.About one in 12 women will be diagnosed with breast cancer in highly developed countries. It is one of the most studied cancers in the U.S., and data from studies of new treatments were featured across this years meeting. Delilah Alvarado '