Cisplatin

Patients lived significantly longer without high-risk disease recurrence or progression after one year of IMFINZI treatment plus Bacillus Calmette-Guérin (BCG) induction and maintenance therapy vs. BCG alone WILMINGTON, DE, USA I May 09, 2025 I Positive high-level results from the POTOMAC Phase III trial showed one year of treatment with AstraZeneca’s IMFINZI ® (durvalumab) plus standard-of-care BCG induction and maintenance therapy demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) for patients with high-risk non-muscle-invasive bladder cancer (NMIBC) compared to BCG induction and maintenance therapy alone.​ The trial was not statistically powered to formally test overall survival (OS) however a descriptive analysis demonstrated no detriment. More than 70% of bladder cancer patients are diagnosed with NMIBC, an early-stage cancer where the tumor is in the tissue that lines the inner surface of the bladder but has not invaded the muscle wall. 1-2 About half of patients with NMIBC are classified as high-risk for disease progression or recurrence because of certain characteristics of their cancer, such as tumor grade, stage and specific tumor features. 3 Maria De Santis, MD, Head of the Interdisciplinary Uro-Oncology Section at Charité Universitätsmedizin Berlin, Germany, and a principal investigator in the POTOMAC trial, said: “These exciting data show that adding one year of durvalumab to the current standard treatment significantly extends the time patients live without high-risk disease recurrence or progression. While most patients with non-muscle invasive bladder cancer are treated with curative intent, 80 percent see their disease return and almost half may require life-altering surgery to remove the bladder, underscoring the urgent need to improve treatment.” Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said: “The positive results for IMFINZIin the POTOMAC trial represent a significant advance that will potentially allow more patients with early-stage bladder cancer to benefit from this important immunotherapy. Building on the NIAGARA data, this outcome demonstrates our strategy of bringing novel therapies to patients with early-stage disease where there is the greatest potential for long-term benefit.” The safety and tolerability of IMFINZI plus BCG induction and maintenance therapy was consistent with the known safety profiles of the individual medicines, with no new safety concerns identified. The addition of IMFINZI did not compromise patients’ ability to complete BCG induction and maintenance therapy. The second experimental arm evaluating IMFINZIplus BCG induction-only therapy compared to BCG induction and maintenance therapy alone did not meet the endpoint of DFS. These data will be presented at a forthcoming medical meeting and shared with global regulatory authorities. IMFINZIis approved in the US and other countries for patients with muscle-invasive bladder cancer (MIBC) based on results from the NIAGARA Phase III trial and continues to be investigated across early and late-stage bladder cancer in various treatment combinations, including in patients with MIBC who are ineligible or refuse to take cisplatin (VOLGA) and in locally advanced or metastatic disease (NILE). Indications: IMFINZI, as a single agent, is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT). IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by IMFINZI continued as a single agent as adjuvant treatment after surgery, is indicated for the treatment of adult patients with resectable (tumors ≥4 cm and/or node positive) NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements. IMFINZI, in combination with IMJUDO and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations. IMFINZI, as a single agent, is indicated for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT). IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). IMFINZI, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC). IMFINZI in combination with IMJUDO is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC). IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) as determined by an FDA-approved test. IMFINZI in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by single-agent IMFINZI as adjuvant treatment following radical cystectomy, is indicated for the treatment of adult patients with muscle-invasive bladder cancer (MIBC). Please see additional Important Safety Information throughout and Full Prescribing Information including Medication Guide for IMFINZI and IMJUDO . Notes Bladder cancer Bladder cancer is the 9th most common cancer in the world, with more than 614,000 cases diagnosed each year. 4 The most common type is urothelial carcinoma, which begins in the urothelial cells of the urinary tract. 2 In 2024, an estimated 125,000 patients were treated for high-risk NMIBC, for which the current standard of care is transurethral resection of bladder tumor (TURBT) followed by administration of BCG directly into the bladder. 5-6 Up to 80% of patients experience disease recurrence within five years, and rates of progression in high-risk patients can be as high as 45%. 2 There is a critical need for treatment options in this curative-intent setting. POTOMAC POTOMAC is a randomized, open-label, multi-center, global Phase III trial evaluating IMFINZIin combination with BCG therapy as a treatment for 1,018 patients with high-risk, BCG-naïve NMIBC who have undergone TURBT prior to randomization. Patients were randomized 1:1:1 to receive IMFINZI plus BCG induction and maintenance therapy, or IMFINZIplus BCG induction-only therapy, versus standard-of-care BCG induction and maintenance therapy. The trial was conducted in more than 120 centers across 12 countries including Canada and others across Europe and Asia. The primary endpoint was DFS, defined as time from randomization to date of first recurrence of high-risk disease or death from any cause, for IMFINZI plus BCG induction and maintenance therapy compared to BCG induction and maintenance therapy alone. Secondary endpoints included DFS for IMFINZI plus BCG induction only therapy versus the comparator arm, as well as OS at five years and safety across both experimental arms of the trial. IMFINZI IMFINZI ® (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses. In addition to its indication in MIBC, IMFINZIis the global standard of care based on OS in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy (CRT). Additionally, IMFINZI is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC, and in combination with a short course of IMJUDO (tremelimumab-actl) and chemotherapy for the treatment of metastatic NSCLC. IMFINZIis also approved for limited-stage small cell lung cancer (SCLC) in patients whose disease has not progressed following concurrent platinum-based CRT; and in combination with chemotherapy for the treatment of extensive-stage SCLC. IMFINZI is also approved in combination with chemotherapy in locally advanced or metastatic biliary tract cancer and in combination with IMJUDO in unresectable hepatocellular carcinoma (HCC). IMFINZIis also approved as a monotherapy in unresectable HCC in Japan and the European Union (EU). In March 2025, perioperative IMFINZI added to standard-of-care chemotherapy met the primary endpoint of event-free survival in the MATTERHORN Phase III trial in resectable gastric and gastroesophageal junction cancers. IMFINZIin combination with chemotherapy followed by IMFINZImonotherapy is approved as a 1st-line treatment for primary advanced or recurrent endometrial cancer (mismatch repair deficient disease only in US and EU). IMFINZIin combination with chemotherapy followed by olaparib and IMFINZIis approved for patients with mismatch repair proficient advanced or recurrent endometrial cancer in EU and Japan. Since the first approval in May 2017, more than 374,000 patients have been treated with IMFINZI. As part of a broad development program, IMFINZIis being tested as a single treatment and in combinations with other anti-cancer treatments for patients with NSCLC, bladder cancer, breast cancer, ovarian cancer and several gastrointestinal cancers. AstraZeneca in immuno-oncology (IO) AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumor immune response and stimulate the body’s immune system to attack tumors. AstraZeneca strives to redefine cancer care and help transform outcomes for patients with IMFINZI as a monotherapy and in combination with IMJUDO as well as other novel immunotherapies and modalities. The Company is also investigating next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer, including cell therapy and T-cell engagers. AstraZeneca is pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. The Company is focused on exploring novel combination approaches to help prevent treatment resistance and drive longer immune responses. With an extensive clinical program, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure. 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 catalyze 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 is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 125 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca . References SOURCE: AstraZeneca

点上方蓝字“ioncology”关注我们，然后点右上角“…”菜单，选择“设为星标”2025 CSCO指南会 微专辑扫描二维码可查看更多内容为积极推动我国临床肿瘤学发展、提高肿瘤医师的临床与科研水平，进一步促进CSCO诊疗指南的制定和推广，2025 CSCO指南会于4月18日在济南盛大开幕。在非小细胞肺癌专场，中国医学科学院肿瘤医院毕楠教授对2025 版《CSCO小细胞肺癌诊疗指南》中放疗部分更新要点进行解读。会议现场，《肿瘤瞭望》特邀毕楠教授接受专访，分享相关更新要点以及放免协同在小细胞肺癌领域探索进展，特此整理，以飨读者。毕楠 教授中国医学科学院肿瘤医院MD.& PhD. 主任医师 博导美国密歇根大学博士后访问学者中国医学科学院肿瘤医院放疗科副主任、胸组主任中华医学会疗分会青委副主委中国抗癌协会放疗专委会青委副主委CSCO理事、NSCLC/SCLC/放疗专委会委员《小细胞肺癌指南》执笔专家《中华放射肿瘤杂志》编委《肿瘤临床与康复》副主编获IASLC ‘Developing Nation Award’国家科技进步二等奖二项省部级科技进步二等奖北京优秀医师等奖项第一／通讯作者在Lancet Oncol、 Ann Oncol、Mol Cancer、Clin Cancer Res、 Cancer Res、JAMA Network Open 等发表论文，成果被ASCO/ ASTRO 、ESMO、CSCO等指南引用，入选ASTRO继续教育CME毕楠教授《肿瘤瞭望》：请您分享下2025版CSCO小细胞肺癌诊疗指南放疗部分主要进行了哪些更新，纳入了哪些重磅研究进展？毕楠教授：2025版CSCO小细胞肺癌诊疗指南放疗部分主要更新要点如下：局限期小细胞肺癌（LS-SCLC ）初始治疗01.LS-SCLC 胸部放疗：辅助放疗更新R1/R2切除需要术后放疗。对于R0切除患者，研究发现，术后N2患者辅助放疗能够提高OS（22个月 vs. 16个月），同时PFS也获得显著提升。此外，亚组分析显示出一致的生存获益，因此推荐术后N2患者接受辅助放疗。一项基于美国国家癌症数据库（NCDB）的回顾性分析显示，与未行辅助放疗相比，N1患者辅助胸部放疗的5年生存率提高5.6%，但差异无统计学意义（P=0.22），基于两组样本量不均衡，且缺少局部复发数据，建议术后N1的患者可行辅助放疗，同步或序贯均可。一项纳入11项回顾性研究7694例行手术切除LS-SCLC患者的分析同样证实了上述结论。02.LS-SCLC 胸部放疗总剂量和分割方案更新一项来自中国 III 期随机对照研究（NCT03214003）对比了高剂量（PTV 给予 45 Gy/30 次，GTV 同步加量至 54 Gy/30 次，每天 2 次）和标准剂量（PTV 均一剂量给予 45 Gy/30 次，每天 2 次）两种超分割方案，结果显示高剂量分割方案可显著延长 OS 和 PFS。03.LS-SCLC 胸部放疗 PCI 更新目前多项循证医学证据表明，广泛起小细胞肺癌（ES-SCLC）患者如果具备核磁筛查随访的条件，可将预防性全脑放疗（PCI）推后，直至出现脑转移后再进行挽救治疗。但对于LS-SCLC，其治疗目标为实现治愈，脑转移严重影响患者预后，因此，个人认为，PCI在LS-SCLC治疗过程中对于疗效提升至关重要。而国外相关单中心回顾性分析研究结果及NCCN指南中指出，对于LS-SCLC患者可先不接受PCI，密切随访直至脑转移发生再进行干预，但对此仍缺乏高级别的循证医学证据，因此，未来仍希望通过开展更大样本的随机对照研究以证实其可靠性。在更多数据出来之前，我想对于年龄＜65岁、接受放化疗疗效较好的LS-SCLC患者，接受PCI巩固治疗对患者预后还是非常重要的。基于此，本次指南中对LS-SCLC 胸部放疗 PCI进行更新，即LS-SCLC 前期经过根治性化疗和胸部放疗，获得较好疗效（PR/CR）的患者，行 PCl，可以降低颅内转移的概率并提高整体生存率。联合免疫巩固治疗，行 PCI 患者 3 年 OS 率为 62.1%，优于未行 PCI 者（50.2%）。此外，本次更新中指出，对于高龄（> 65 岁），PS>2 分，有神经认知功能受损的患者不建议行 PCI。治疗前行脑核磁共振（MR）检查和随访，PCI 获益可能有所下降，需要开展前瞻性随机对照研究。未行 PCI 的患者，建议密切随诊颅内情况，如无禁忌证，第一年推荐每 3 个月复查脑 MR，以后推荐每半年复查脑 MR，以及时发现脑转移病灶行挽救放疗。广泛期小细胞肺癌（ES-SCLC） 胸部放疗注释更新标准一线阿得贝利单抗+依托泊苷/顺铂或卡铂后，序贯TRT（大于等于30Gy/10次或大于等于50Gy/25次），同期并维持阿得贝利单抗治疗，毒性可接受，ORR为71.6%，中位PFS为10.1个月，OS达21.4个月）。放疗并发症的处理01.在“一、放射性肺损伤”的注释部分中增加如下描述II 期研究发现吡非尼酮联合标准疗法能够改善放射性肺损伤（RILI）患者的肺功能、轻到中度放射性纤维化、无急性肺恶化生存。02.在“四、放射性皮肤损伤”的注释部分中修改完善如下描述针对放射性皮肤损伤，应保护皮肤损伤部位，防止外伤和各种物理或化学刺激；消除炎症、防止继发感染，促进组织愈合；对经久不愈的溃疡，可手术治疗；在合并有急性放射病时，全身和局部病变可互相影响，因此，在进行局部治疗的同时，应积极进行全身治疗。03.在“五、放射性口咽黏膜炎”的注释部分中新增如下描述镇痛治疗是放射性口腔黏膜炎管理的关键措施，以局部用药为主。利多卡因含漱和芬太尼鼻喷雾是缓解疼痛的有效方法。中度疼痛推荐小剂量控释羟考酮，提高生活质量。疼痛加重时，推荐使用吗啡或芬太尼等镇痛药。《肿瘤瞭望》：请您结合放免协同机制及相关临床研究进展，谈谈您如何看待免疫治疗背景下TRT对于ES-SCLC患者的临床价值？毕楠教授：尽管化免联合显著改善了ES-SCLC患者的生存，但疗效仍需进一步提升。个人认为，胸部放疗（TRT）之所以可以改善免疫治疗背景下ES-SCLC的临床获益，主要原因在于，ES-SCLC属于冷肿瘤，PD-L1表达较低，TRT可以通过上调PD-L1表达以改善冷肿瘤的免疫微环境，进而产生协同效应，但目前这种协同效应仍以全身治疗为主。现阶段，TRT在ES-SCLC治疗领域探索主要进展包括两个方面，首先，由山东省肿瘤医院于金明院士团队牵头开展的首项针对ES-SCLC患者评估阿得贝利单抗联合化疗序贯胸部放疗（TRT）的前瞻性II期研究。研究结果显示，阿得贝利单抗联合化疗和序贯TRT可为ES-SCLC患者带来明显生存获益，且安全性良好。该研究表明在开展化疗联合免疫疗法同时，增加胸部放疗可提高治疗ES-SCLC的疗效。其中，需要强调的是，在此种情况下，应一定注意平衡好TRT疗效与毒性之间的关系。因为在化疗时代，相关研究表明，ES-SCLC巩固TRT高剂量与低剂量之间对比疗效没有显著提升。而本项研究结果亦表明，高剂量TRT相较于较低剂量并没有带来疗效显著提升的同时毒性较大，因此，个人认为，对于ES-SCLC巩固TRT前需进行风险分层，对于全身肿瘤负荷较轻或化免联合治疗后局部有明显肿瘤残存的患者，给予相对安全剂量的TRT或可带来更多临床获益。其次为四川大学华西医院卢铀教授团队开展的探索低剂量放疗（LDRT15Gy/5f）协同增强免疫治疗ES-SCLC新策略的Ⅱ期研究，该研究首次阐明低剂量放疗协同增强免疫治疗小细胞肺癌疗效的潜在机制，并开展前瞻性II临床研究验证了低剂量放疗联合免疫+化疗一线治疗广泛期小细胞肺癌的安全性和有效性，为广泛期小细胞肺癌患者提供一种潜在的临床治疗策略。期待未来更多Ⅲ期临床研究数据公布，以期通过更高级别的循证医学证据证实ES-SCLC巩固TRT的临床疗效。《肿瘤瞭望》：基于2025 CSCO小细胞肺癌诊疗指南放疗部分的更新，请您谈谈未来小细胞肺癌放射治疗领域的探索方向及发展趋势如何？毕楠教授：目前对于SCLC治疗在疗效提升层面仍存在一定的优化空间。内科专家多从创新药研发及新药联合策略方向寻求突破。作为一名放疗科医生，个人认为放疗层面主要是通过不断精进放疗技术降低毒性，进而与创新药物相联合，实现“1+1＞2”的效果。其中，在与其他治疗手段相联合层面，治疗时序问题值得关注。如ADRIATIC研究探索了完成同步放化疗（cCRT）后，度伐利尤单抗巩固治疗（联合或不联合tremelimumab）的疗效和安全性，该研究结果证实了cCRT后免疫巩固治疗可改善LS-SCLC患者胸外和胸内进展情况。尽管如此，近期NRG-LU005研究探索了同步放化疗（cCRT）联合阿替利珠单抗用于LS-SCLC的治疗效果，结果显示同步放化疗联合免疫治疗并没有提高患者的生存率，反而在中位 OS 上，联合治疗组低于单纯同步放化疗组 ，由此可见，放化疗同步联合免疫治疗或不能为SCLC带来更好的疗效，基于现阶段研究结果，该治疗策略尚未被推荐。谈及未来发展趋势，首先就是前面所提及的当前正在积极开展的几项关于化免诱导后序贯同步化放疗±免疫巩固的治疗模式的临床Ⅲ期研究，期待相关研究数据公布以期为患者带来更多临床获益。其次，探索用于患者精准风险分层及可预测疗效的生物标志物仍为SCLC领域研究重点。目前SCLC治疗缺乏有效的预测生物标志物及合适的分层方法，难以实现精准治疗 。未来亟需通过更大样本量的队列研究探索潜在可预测的生物标志物，用于指导临床实践，以进一步提升SCLC临床疗效。（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。