Cisplatin

引言「2025 CSCO 指南会」于 2025 年 4 月 18 日至 19 日在济南山东大厦举办。本届大会由中国临床肿瘤学会（CSCO）、北京市希思科临床肿瘤学研究基金会联合主办，会议上发布了最新版指南。其中，来自吉林省肿瘤医院柳影教授、吉林省肿瘤医院李慧教授、中国医学科学院肿瘤医院毕楠教授就《2025 版 CSCO：小细胞肺癌诊疗指南更新要点》进行了解读。「丁香园肿瘤时间」现将相关要点整理如下，以飨读者。PART 01 内科部分更新解读1 广泛期 SCLC 新增 I 级推荐➤ 广泛期 SCLC 初始治疗新增 I 级推荐① 替雷利珠单抗 + 卡铂或顺铂 + 依托泊苷 4 周期后替雷利珠单抗维持治疗由 III 级推荐修订为 I 级推荐（优选，1A 类）；② 特瑞普利单抗 + 卡铂或顺铂 + 依托泊苷 4-6 周期后特瑞普利单抗维持治疗由 III 级推荐修订为 I 级推荐（优选，1A 类）。值得注意的是，目前广泛期 SCLC 一线治疗已有了新标杆和新选择，治疗效果明显提升，并实现了医保覆盖，具体如下：① RATIONALE-312 研究：替雷利珠单抗联合化疗实现 SCLC 医保覆盖；② EXTENTORCH 研究：特瑞普利单抗联合化疗实现 SCLC 医保覆盖；③ ETER701 研究是免疫治疗联合化疗基础上增加多靶点抗血管药物治疗模式的首次成功，OS 达到新高度。2 复发 SCLC 二线治疗新增 I 级推荐芦比替定由 III 级推荐改为 I 级推荐（2A 类），其中国桥接研究 LY01017/CT-CHN-101，NMPA 批准芦比替定二线治疗 SCLC 的适应证。3 局限期 SCLC 的初始治疗新增 II 级推荐超过 T1～2N0 的 LS-SCLC 患者，新增同步放化疗后未进展者接受度伐利尤单抗巩固治疗（1 类。值得注意的是，度伐利尤单抗 ±tremelimumab 或者安慰剂巩固治疗 LS-SCLC 的 III 期研究（ADRIATIC 研究）结果于 2024 年荣登 NEJM 顶刊。4 广泛期 SCLC 生存随访及维持治疗注释部分新增、更新➤ 随访新增注释：① ASTRUM-005 研究 3 年随访数据：经 31.6 个月中位随访，斯鲁利单抗联合化疗组和对照组 3 年的 OS 率分别为 24.6% 和 9.8%；② IMpower133 研究生存随访：IMpower133 研究中位随访 59.4 个月，阿替利珠单抗联合化疗 5 年的 OS 率达到 12%，6 年生存率达 11%，可见部分 ES-SCLC 患者一旦对阿替利珠单抗具有反应，可实现长期的肿瘤缓解，达到临床治愈。➤ 治疗维持新增注释：① 广泛期 SCLC 维持治疗 ——IMpower133 研究：探索性分析发现，IMpower133 研究中，从维持治疗开始阿替利珠单抗组和安慰剂组的 OS 分别为 12.5 个月和 8.4 个月，研究认为阿替利珠单抗的维持治疗对 IMpower133 研究中免疫联合化疗组 OS 的获益有重要贡献。② 广泛期 SCLC 维持治疗 ——DeLLphi-303 研究：DeLLphi-303 研究是一项塔拉妥单抗联合 PD-L1 抑制剂维持治疗广泛期 SCLC 的 1B 期研究，塔拉妥单抗联合 PD-L1 抑制剂维持治疗的 PFS 为 5.6 个月，安全性良好，为正在进行的塔拉妥单抗联合度伐利尤单抗维持治疗的 3 期研究 DeLLphi-305 研究提供了支持，该研究也可能成为 SCLC 免疫治疗下一个突破口。③ 广泛期 SCLC 的维持治疗 ——DURABLE 研究：DURABLE 研究是一项度伐利尤单抗联合安罗替尼对比度伐利尤单抗维持治疗的 2 期研究，研究显示，从诱导治疗开始，度伐利尤单抗联合安罗替尼维持治疗和度伐利尤单抗单药维持治疗组的 PFS 分别为 9.0 个月和 5.6 个月，OS 分别为 20.4 个月和 15.4 个月，这些研究提示免疫联合多靶点抗血管药物维持治疗是具有前景的研究方向。➤ 广泛期 SCLC 研究临床治疗数据更新注释1) 广泛期 SCLC 一线治疗序贯胸部放疗标准一线阿得贝利单抗 + 依托泊苷/顺铂或卡铂治疗后，序贯 TRT（230 Gy/10 次或 ≥ 50 Gy/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。2) 广泛期 SCLC 骨髓抑制的支持治疗曲拉西利预防 SCLC 一线治疗骨髓抑制已经纳入医保，将极大地降低 SCLC 化疗患者骨髓保护治疗的费用支出，同时改善 SCLC 患者的生活质量。5 药物注释部分新增➤ 创新药物研发：靶向 DLL3/CD3 双特异 T 细胞连接器抗体塔拉妥单抗新增靶向 DLL3 和 CD3 的双抗药物，2024 年 5 月，FDA 加速批准塔拉妥单抗治疗复发小细胞肺癌，成为复发 SCLC 新的治疗选择。➤ B7 H3 ADC 药物新增 I-DXd 治疗复发 SCLC 的 II 期研究结果；及 ARTEMIS-001 研究结果。➤ B7 H3 ADC 药物及 DLL3 ADC 药物新增 YL201 的 I 期研究结果、DB 1311/BNT324 的 I 期研究结果及 ZL-1310 I 期研究结果。➤ Trop-2 ADC 药物新增 Trop-2 的 ADC 在复发 SCLC 的研究结果：①TROPiCS-03 研究：2024 WCLC OA04.04；②SHR-A1921 相关研究：2024 WCLC OA04.05➤ 靶向 SEZ6 的 ADC 药物新增 ABBV-706 在 SCLC 的研究结果（2024 ASCO 3001）。6 要点总结➤ 一线治疗实现了新突破在广泛期 SCLC 一线有三个免疫靶向药物获批上市，替雷利珠单抗、特瑞普利单抗联合化疗获批 SCLC 医保适应证，这也是首次在 SCLC 领域免疫治疗纳入医保适应证，惠及广大了 SCLC 患者。➤ 局限期 SCLC 实现了里程碑式的跨越国际的 ADRIATIC 研究开创了 LS-SCLC 崭新的治疗模式，打破了 LS-SCLC 几十年来无新药获批的局面。➤ 二线治疗建立新标准芦比替定基于中国的桥接研究，获批 NMPA 适应证，改变了中国 SCLC 复发后的二线治疗几十年未突破的局面。➤ 广泛期 SCLC 免疫治疗长期生存数据的更新显示了免疫治疗显著且稳健的长期生存获益，为 ES-SCLC 临床实践提供了更高价值和更有力的循证医学证据。➤ 创新型抗肿瘤药物靶向 DLL3/CD3 双特异 T 细胞连接器抗体、抗体偶联药物等药物研发为 SCLC 患者带来新的希望，未来有望实现更大的突破。PART 02放疗部分更新要点1 LS-SCLC 初始治疗➤ 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），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。➤ 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。➤ LS-SCLC 胸部放疗 PCI 更新① 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%）。② 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。2 ES-SCLC 一线治疗➤ ES-SCLC 放疗此次表格无修订：图 1. 广泛期 SCLC—— 放疗概览（图源：2025 CSCO 小细胞肺癌诊疗指南更新解读会）➤ 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（≥ 30 Gy/10 次或 ≥ 50 Gy/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）。3 放疗并发症的处理➤ 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。➤ 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。➤ 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。PART 03病理及分子病理更新新增内容 1：在肺神经内分泌肿瘤低、中、高 3 个级别中，新增中-高级别；在分化好的 2 个类癌类型中，新增 1 个类型；新增内容 2：根据基因组特征，将大细胞神经内分泌癌进一步分为 3 型，SCLC 样、NSCLC 样、类癌样。图 3. 神经内分泌肿瘤分类（图源：2025 CSCO 小细胞肺癌诊疗指南更新解读会）总结2025 年 CSCO 小细胞肺癌指南在内科、放疗及病理方面均有重要更新。在内科方面，广泛期 SCLC 一线治疗新增替雷利珠单抗和特瑞普利单抗联合化疗为 I 级推荐，并实现医保覆盖。复发 SCLC 二线治疗新增芦比替定为 I 级推荐。局限期 SCLC 新增度伐利尤单抗巩固治疗为 II 级推荐。此外，广泛期 SCLC 的生存随访、维持治疗及创新药物研发如靶向 DLL3/CD3 双特异抗体等均有新进展。在放疗部分，广泛期 SCLC 胸部放疗注释有所更新，在放疗并发症的处理方面新增相关内容，进一步强调了个体化治疗。在病理方面，在肺神经内分泌肿瘤低、中、高 3 个级别中，新增中-高级别，并将大细胞神经内分泌癌进一步分为 3 型。总体来说，这些更新有望为小细胞肺癌患者提供更多、更有效的治疗选择，改善患者生存及预后。本文首发于丁香园旗下专业平台：丁香园肿瘤时间整理：明晓；编辑：Bree题图：丁香园创意团队投稿：sunjiamei@dxy.cn

HONG KONG, April 24, 2025 /PRNewswire/ -- Akeso, Inc. (9926.HK) ("Akeso" or the "Company") is excited to announce that the U.S. Food and Drug Administration (FDA) has approved its differentiated PD-1 monoclonal antibody, penpulimab-kcqx, in combination with cisplatin or carboplatin and gemcitabine for the first-line treatment of adult recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC). FDA also approved penpulimab-kcqx as a single agent for adults with metastatic non-keratinizing NPC with disease progression on or after platinum-based chemotherapy and with least one other prior line of therapy. Penpulimab-kcqx was developed independently by Akeso, with further development and commercialization managed through a joint venture with Chia Tai-Tianqing Pharmaceutical Group. This milestone marks penpulimab-kcqx as Akeso's first internally developed innovative biologic to receive FDA approval. The approval underscores the robust clinical research behind penpulimab-kcqx and marks Akeso's successful entry into the United States regulatory system for the first time. This achievement highlights the company's innovative drug development capabilities and its commitment to adhering to the highest international standards in pharmaceutical quality management. The FDA's approval of penpulimab-kcqx validates Akeso's international drug development strategy and expansion capabilities. This approval lays a strong foundation for Akeso's continued clinical development efforts in the global therapeutics markets. Penpulimab-kcqx has been approved in China for two indications: 1. first-line treatment of advanced NPC, and 2. second or later line treatment of advanced NPC. The recent FDA approval of penpulimab-kcqx offers a new, immunotherapy option for advanced NPC patients in the US. The FDA approval is based on the international Phase III clinical trial AK105-304 and the pivotal AK105-202 study, which supported the two Biologics License Application (BLA) for penpulimab-kcqx. These studies demonstrated the drug's clinical benefits and favorable safety profile across two stages of treatment for metastatic NPC. AK105-304 is a randomized, double-blind, international Phase III trial that enrolled NPC patients of diverse ethnicities. The data will be presented at the 2025 American Association for Cancer Research (AACR) Annual Meeting. Previously, the FDA granted penpulimab-kcqx Breakthrough Therapy Designation (BTD), Orphan Drug Designation (ODD), and Fast Track Designation (FTD) for NPC treatment, highlighting the critical unmet need for this therapy. According to the WHO 2020 Global Cancer Statistics, over 133,000 new NPC cases are diagnosed annually worldwide, with more than 70% of the patients presented with locally advanced disease. Recurrent or metastatic NPC has a poor prognosis and limited survival. Penpulimab-kcqx's FDA approval will expand the number of NPC patients that can benefit from its treatment. Prof. Chaosu Hu, Principal Investigator of penpulimab-kcqx from Fudan University Shanghai Cancer Center, commented: "This milestone enhances international treatment guidelines for advanced NPC and extends the benefits of China's innovations to global patients, ultimately reshaping the treatment landscape for metastatic NPC worldwide." Prof. Xiaozhong Chen, Investigator of penpulimab-kcqx from Zhejiang Cancer Hospital, added: "The FDA approval of penpulimab-kcqx confirms its high efficacy and low toxicity, positioning China's innovative drug development in alignment with international standards." Dr. Yu Xia, Founder, Chairwoman, President & CEO of Akeso, expressed: "We are very excited by the approval of penpulimab-kcqx's approval in the US FDA for first line and later line NPC. Beyond reaching our first international regulatory milestone, this approval also provides an important immunotherapy treatment option for patients with NPC in the United States. The FDA approval of penpulimab-kcqx not only highlights the quality of our innovation but also underscores Akeso's focus on delivering treatments for difficult to treat cancers for patients around the world. We are deeply grateful to all the researchers, participants, and patients who have contributed to this success. Akeso will continue to advance first and best in class therapies, including bispecific antibodies and CD47 inhibitors, challenge global standards of care and unlocking the full potential of our pipeline for cancer patients everywhere." Forward-Looking Statement of Akeso, Inc. This announcement by Akeso, Inc. ( 9926. HK) contains "forward-looking statements". These statements reflect the current beliefs and expectations of Akeso's management and are subject to significant risks and uncertainties. There can be no assurance that penpulimab-kcqx or other pipeline candidates will obtain the required regulatory approvals or achieve commercial success. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company's patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. Akeso does not undertake any obligation to publicly revise these forward-looking statements to reflect events or circumstances after the date hereof, except as required by law. Please see Prescribing Information for penpulimab-kcqx at when it is posted. About Akeso Akeso (HKEX: 9926.HK) is a leading biopharmaceutical company committed to the research, development, manufacturing and commercialization of the world's first or best-in-class innovative biological medicines. Founded in 2012, the company has created a unique integrated R&D innovation system with the comprehensive end-to-end drug development platform (ACE Platform) and bi-specific antibody drug development technology (Tetrabody) as the core, a GMP-compliant manufacturing system and a commercialization system with an advanced operation mode, and has gradually developed into a globally competitive biopharmaceutical company focused on innovative solutions. With fully integrated multi-functional platform, Akeso is internally working on a robust pipeline of over 50 innovative assets in the fields of cancer, autoimmune disease, inflammation, metabolic disease and other major diseases. Among them, 24 candidates have entered clinical trials (including 15 bispecific/multispecific antibodies and bispecific ADCs. Additionally, 7 new drugs are commercially available, and 4 new drugs with 4 new indications are under regulatory review for approval. Through efficient and breakthrough R&D innovation, Akeso always integrates superior global resources, develops the first-in-class and best-in-class new drugs, provides affordable therapeutic antibodies for patients worldwide, and continuously creates more commercial and social values to become a global leading biopharmaceutical enterprise. For more information, please visit and follow us on Linkedin. SOURCE Akeso, Inc. 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