A Phase 1b Trial of Adaptive Stereotactic Body Radiotherapy in Combination with Durvalumab (MEDI4736), Platinum, and Etoposide in Extensive Stage Small Cell Lung Cancer

This is trial studying the safety of adaptive stereotactic body radiotherapy (SBRT) combined with durvalumab immunotherapy, platinum chemotherapy, and etoposide chemotherapy in platinum refractory extensive stage small cell lung cancer (SCLC).

开始日期2025-12-31

申办/合作机构

University of Maryland Baltimore

[+1]

NCT06401330

/ Recruiting临床3期IIT

Risk Adapted Treatment of Unilateral Favorable Histology Wilms Tumors (FHWT)

This phase III trial studies using risk factors in determining treatment for children with favorable tissue (histology) Wilms tumors (FHWT). Wilms Tumor is the most common type of kidney cancer in children, and FHWT is the most common subtype. Previous large clinical trials have established treatment plans that are likely to cure most children with FHWT, however some children still have their cancer come back (called relapse) and not all survive. Previous research has identified features of FHWT that are associated with higher or lower risks of relapse. The term "risk" refers to the chance of the cancer coming back after treatment. Using results of tumor histology tests, biology tests, and response to therapy may be able to improve treatment for children with FHWT.

开始日期2025-12-23

申办/合作机构

The Children's Oncology Group Foundation, Inc.

NCT06769126

/ Not yet recruiting临床2期IIT

PRISM: PRecIsion in SCLC Via a Multicohort Study: Randomized Phase II Studies Evaluating Maintenance Durvalumab With or Without Biomarker-Directed Therapy for Extensive Stage Small Cell Lung Cancer (ES-SCLC)

This phase II trial tests how well biomarker tests on patients tumor tissue works in selecting personalized treatments for patients with extensive stage small cell lung cancer (ES-SCLC). Biomarker tests look for certain features in cancer cells that may give doctors more information about what is driving cancer and how to treat it. Based on the biomarker test results, study doctors can determine the subtype of ES-SCLC that study treatments can target. This study also tests different types of maintenance treatment for ES-SCLC with drugs durvalumab, saruparib, ceralasertib or monalizumab. Maintenance treatment is given after initial treatment and is given to help keep the cancer under control and prevent it from getting worse. Immunotherapy with monoclonal antibodies, such as durvalumab and monalizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Saruparib is a PARP inhibitor. PARP is a protein that helps repair damaged deoxyribonucleic acid (DNA). Blocking PARP may prevent cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Ceralasertib may stop the growth of tumor cells and may kill them by blocking some of the enzymes needed for tumor cell growth. Giving biomarker selected personalized maintenance treatment with durvalumab, saruparib, ceralasertib or monalizumab may work better in treating patients with ES-SCLC.

开始日期2025-09-08

申办/合作机构

SWOG

[+1]

100 项与依托泊苷相关的临床结果

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100 项与依托泊苷相关的转化医学

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100 项与依托泊苷相关的专利（医药）

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34,855

项与依托泊苷相关的文献（医药）

2025-12-31·NMC case report journal

A Primary Spinal Intramedullary Mixed Germ Cell Tumor: A Case Report and Literature Review

Article

作者: SHIMAUCHI-OHTAKI, Hiroya ; HORIGUCHI, Keishi ; HIRATO, Junko ; NAKATA, Satoshi ; HONDA, Fumiaki ; YOKOO, Hideaki ; OYA, Soichi ; GOTO, Yuta ; TOMOMASA, Ran ; NAKAMURA, Shunsuke

Central nervous system germ cell tumors are rare and account for 2% to 3% of all central nervous system tumors in Japan. Here, we report an extremely rare case of a primary spinal intramedullary mixed germ cell tumor. A 33-year-old man presented with a chief report of dysuria and numbness in the right lower extremity. Magnetic resonance imaging revealed a mass lesion on the left side of the intramedullary spinal cord at the Th10-11 vertebral body level with hyperintensity on T2-weighted images, isointensity on T1-weighted images, and uniform contrast in gadolinium. Cerebrospinal fluid examination revealed a few atypical cells. Although tumor removal using the posterior median sulcus approach was attempted, only a biopsy was performed because intraoperative rapid pathology suggested a possible diagnosis of germinoma. Permanent pathology revealed a mixed germ cell tumor (mainly comprising a germinoma with a yolk sac tumor). Postoperatively, cerebrospinal irradiation and 8 courses of the carboplatin and etoposide regimen were administered. No recurrence or new lesions were observed on magnetic resonance imaging at 94 months postoperatively. Our extensive literature search found only 4 cases of a mixed germ cell tumor of primary intramedullary origin in the spinal cord. Most spinal germ cell tumors described in the literature are either germinomas or mature teratomas; however, mixed germ cell tumors can also occur, albeit infrequently. Although additional cases need to be accumulated, our case suggests that yolk sac elements in spinal mixed germ cell tumors might not be directly associated with poor life expectancy.

2025-12-31·ANNALS OF MEDICINE

Construction of a novel prognostic model based on lncRNAs-related to DNA damage repair for predicting the prognosis of clear cell renal cell carcinoma

Article

作者: Chen, Peng ; Li, Jian ; Tian, Renli

BACKGROUND:

CcRCC has the characteristics of high aggression, high metastasis, high mortality, wide tumour heterogeneity and variable clinical course. The purpose of this study was to explore the potential value of lncRNAs-related to DNA damage repair (DDR) in predicting the prognosis of ccRCC by construction and verification a novel prognostic model.

METHODS:

RNA-seq data and clinical data of ccRCC were downloaded from public databases. Subsequently, Pearson correlation analysis and differential expression analysis were performed to identify DElncRNAs-related to DDR. Then, through univariate Cox analysis and LASSO analysis, the DElncRNAs-related to DDR associated with prognosis were screened for the construction of novel risk score prognostic model. In addition, functional annotation, tumour mutation burden, immune correlation and drug sensitivity analyses were performed based on risk score to assess the characteristics of patients in different risk score groups.

RESULTS:

Based on univariate Cox analysis and LASSO analysis, four best DElncRNAs-related to DDR were selected. Subsequently, a novel risk score prognostic model based on these four DElncRNAs was constructed through LASSO. Multivariate Cox analysis showed that risk score and age were independent prognostic factors for ccRCC (p < 0.05). Functional enrichment analysis showed that DDR-related biological processes were mainly enriched in the high risk group. The highly mutated genes in the high and low risk groups were the same (VHL, PBRM1 and TTN), but they also had their own unique mutated genes. Pearson correlation analysis showed that the risk score was significantly (p < 0.05) positively correlated with the infiltration degree of CD8 T cells evaluated by six algorithms. In addition, it was found that the high and low risk groups had different sensitivities to the drugs Etoposide, Imatinib, Sorafenib, Bosutinib and Sunitinib.

CONCLUSION:

A novel prognostic model was constructed based on four DElncRNAs-related to DDR. The model has satisfactory accuracy in predicting survival of ccRCC patients.

2025-08-01·JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

Simultaneous analysis of various anticancer drugs by supercritical fluid chromatography-mass spectrometry. Part I: Optimization of chromatographic separation

Article

作者: Guillarme, Davy ; Rudaz, Serge ; Fleury-Souverain, Sandrine ; Bonnabry, Pascal ; Nguyen, Nathalie

This work presents a generic SFC-MS method for the simultaneous analysis of 22 anticancer drugs (fluorouracil, busulfan, cyclophosphamide, cytarabine, dacarbazine, daunorubicin, docetaxel, doxorubicin, epirubicin, etoposide, gemcitabine, idarubicin, ifosfamide, irinotecan, methotrexate, paclitaxel, pemetrexed, raltitrexed, topotecan, treosulfan, vinblastine, vincristine). The separation conditions were optimized by screening nine stationary phases (2-picolylamine, bare hybrid silica, 2-ethylpyridine, fluoro-phenyl, octadecyl, diethylamine, diol, 1-aminoanthracene, zwitterionic modification), evaluating additives effects (2-5 % water, 20-50 mM ammonium formate, 0-1 mM ammonium fluoride), and adjusting the organic modifier composition (methanol, ethanol, isopropanol, acetonitrile). The optimized SFC-MS method successfully analyzed 22 anticancer drugs, along with 5 additional challenging compounds (azacitidine, mitomycin, cisplatin, oxaliplatin, carboplatin), in 12 min, using a diol column (100 × 3 mm, 1.7 µm) and a gradient of 2-100 % methanol containing 2 % water and 50 mM ammonium formate. To overcome overpressure generated by high organic solvent content, a backpressure gradient (110-150 bar) and a flow rate gradient (0.6-1.5 mL/min) were applied. The diol column was selected as the most promising based on five predefined chromatographic criteria. Additives with 5 % water or ammonium fluoride were excluded due to overpressure and signal loss, respectively. Increasing ammonium formate concentration improved peak symmetry by 29 %. For the organic modifier, pure methanol was chosen since ternary mixtures led to system overpressure without improving separation. Comparison with the LC-MS method using real samples confirmed the potential applicability of the SFC method, as the same trace compounds were detected with comparable concentrations. Sensitivity optimization and method validation will be discussed separately in a later paper.

680

项与依托泊苷相关的新闻（医药）

2025-04-09

·梅斯医学

年轻女性高热40℃不退、全身酸痛，抗生素治疗无效，以为是普通感冒，没想到竟是这种这种“伪装大师”疾病！

32岁的市场策划经理林蕾（化名）在过去几个月中频繁“高烧不退”，体温动辄飙到40℃以上，吃退烧药也难以缓解。起初她以为只是“反复感冒”，直到伴随关节疼痛、咽痛、皮疹反复发作，连握笔、敲键盘都变得吃力。尤其奇怪的是，每次高烧前后，林蕾的手腕、膝盖、踝关节都出现游走性疼痛，皮肤还会泛出一阵淡粉色的斑疹，下午或晚上尤为明显。公司同事开始议论她“是不是风湿病”，但多次风湿免疫相关指标检查都为阴性。她甚至一度被误认为是精神因素引发的“疑病症”。最终在三甲医院风湿免疫科就诊时，医生发现她白细胞总数高达13×10⁹/L（中性粒细胞占比86%），CRP、ESR、铁蛋白显著升高，肝酶轻度异常，ANA和RF阴性，小剂量抗生素治疗无效。进一步排查排除了感染、肿瘤、自身免疫性疾病等常见原因，结合其长期不明原因高热、典型皮疹、关节痛等表现，最终确诊为成人斯蒂尔病（AOSD）。什么是成人斯蒂尔病成人斯蒂尔病（AOSD）是一种少见的、病因不明的全身性自身炎症性疾病，以发热、皮疹、关节炎或关节痛、咽痛、肝脾及淋巴结肿大、外周血白细胞总数及中性粒细胞比例增高等为主要表现。临床表现成人型Still病（AOSD）临床表现复杂，以发热、关节炎和皮疹为三大典型症状。发热几乎见于所有患者，常为傍晚或夜间骤升至高热，呈弛张热型，常伴寒战，可自行退热且退热后状态良好。关节痛或关节炎多见于2/3以上患者，症状随热程波动，常累及膝、腕等大关节，晚期可致关节破坏。皮疹多为与发热伴发的三文鱼色斑疹或斑丘疹，好发于四肢近端和躯干，亦可见非典型皮损如色素性丘疹、固定性荨麻疹等，提示病情更重、激素反应差。肌痛较为常见，但多无肌酶升高。咽痛常为早期症状，随热程波动，体检可见咽充血、滤泡增生，咽拭子培养阴性。部分患者可有脾大和对称性淋巴结肿大，需鉴别淋巴瘤；肝脏受累者约八成，表现为肝酶升高至严重肝衰，需排除药物因素。心肺受累以浆膜炎和肺实质病变为主，较少见。严重并发症如巨噬细胞活化综合征（MAS）需高度警惕，表现为高热不退、血细胞减少、纤维蛋白原下降等，常因剧烈炎症或继发感染引起。此外，AOSD亦可并发血栓性微血管病、DIC、急性呼吸窘迫综合征等。诊断AOSD缺乏特异性诊断标志，目前主要依赖临床标准进行诊断，其中最常用的是Yamaguchi标准。该标准敏感度达96.3%，特异度为98.2%，前提是排除感染、肿瘤及其他风湿性疾病。Yamaguchi标准包括：主要标准：① ≥39℃发热持续≥1周；② 关节痛持续≥2周；③ 典型皮疹；④ 白细胞≥10×10⁹/L，且中性粒细胞＞80%。次要标准：① 咽痛；② 淋巴结或脾肿大；③ 肝功能异常；④ 类风湿因子及抗核抗体阴性。排除标准：感染（如败血症、EB病毒）、恶性肿瘤（如淋巴瘤）、其他风湿病（如系统性血管炎）。诊断成立条件：在排除其他疾病后，符合5项或以上标准，且至少包括2项主要标准，即可诊断AOSD。治疗AOSD治疗以经验性为主，依据病情轻重和是否合并并发症选择方案。轻症可先用非甾体抗炎药，但多数患者疗效有限，仅用于短期对症控制，注意药物不良反应。激素是治疗一线药物，常用泼尼松0.5~1 mg/kg·d 起始治疗，疗效显著，逐步减量，严重病例可考虑甲泼尼龙冲击。对激素无效或减量复发者，应联合DMARDs，首选甲氨蝶呤，其次为环孢素A、来氟米特、羟氯喹等，注意各自副作用。生物制剂为难治性AOSD提供新选择。TNF抑制剂适用于关节炎型AOSD，英夫利西单抗或优于依那西普。IL-6抑制剂托珠单抗可改善全身和关节症状，疗效稳定。IL-1抑制剂如阿那白滞素、卡纳单抗、利纳西普疗效明确，适用于系统型AOSD，卡纳单抗维持时间长，适合激素依赖者。JAK抑制剂如托法替布、巴瑞替尼在小样本中显示出良好疗效，需警惕肝酶和血脂升高等不良反应。静脉注射免疫球蛋白适用于激素依赖或合并MAS等危重患者，可辅助缓解病情，对妊娠期患者亦有益。对难治或合并暴发性肝衰、MAS等严重并发症者，需加大激素剂量，联合两种DMARDs或联合生物制剂、JAK抑制剂，必要时参考HLH-2004方案使用依托泊苷，并可辅以IVIG治疗。参考资料：1.Mitrovic S , Fautrel B . New markers for adult-onset Still′s disease[J]. Joint Bone Spine, 2018,85(3):285-293. DOI: 10.1016/j.jbspin.2017.05.011 .2.朱小霞, 李芹, 王悦, 等. 成人斯蒂尔病诊疗规范[J]. 中华内科杂志, 2022, 61(4): 370-376. DOI: 10.3760/cma.j.cn112138-20211115-00806.3.Hu QY , Zeng T , Sun CY ,et al. Clinical features and current treatments of adult-onset Still′s disease: a multicentre survey of 517 patients in China[J]. Clin Exp Rheumatol, 2019,37Suppl 121(6):52-57.来源 | 梅斯医学编辑 | wanny神经系统罕见病交流群↓点击下方“阅读原文”，下载梅斯医学APP吧！

临床研究

2025-04-08

·ioncology

大咖辩论：双特异性抗体会取代PD-(L)1抑制剂吗？丨IASLC肺癌靶向治疗会议

点击蓝字关注我们自2015年FDA首次批准纳武利尤单抗治疗晚期非小细胞肺癌（NSCLC）以来，临床医生已见证了使用抗PD-(L)1药物在一线和二线治疗中抑制癌细胞使总生存（OS）有所提高。[1]这十年的统治地位是否即将结束？双特异性抗体是否会取代PD-(L)1药物成为肺癌免疫治疗的主力？在2月20日举行的国际肺癌研究协会（IASLC）肺癌靶向治疗会议上，来自加州大学戴维斯分校的Jonathan W. Riess教授与密歇根大学的Greg Kalemkerian教授就此展开精彩正反辩论。▲Jonathan Riess, MD▼Greg Kalemkerian, MD正方：双特异性抗体即将加冕免疫治疗王冠Dr. Riess阐述三个核心论点捍卫其立场：1.双特异性抗体可靶向癌症免疫循环（cancer immunity cycle）的多个组成部分（包括阻断PD-1/PD-L1）双特异性抗体具有独特的能力，可以对一系列刺激/抑制免疫信号进行组合攻击，包括阻断免疫检查点、共刺激激活免疫细胞以及与细胞因子和炎症因子结合。图1. 双特异性抗体的特点2.作用机制的优势增强，例如产生协同结合（cooperative binding）双特异性抗体已显示出机制优势，例如协同结合。PD-1/VEGF双抗依沃西单抗的研究中就观察到这种机制优势。依沃西单抗与VEGF的协同结合可使PD-1亲和力（PD-1 affinity）增加18倍以上，而依沃西单抗与PD-1的协同结合可使VEGF亲和力增加4倍以上。[2]图2. 依沃西单抗的协同结合活性3.试验初始数据有前景随机III期头对头研究HARMONi-2显示，在PD-L1阳性NSCLC患者中，依沃西单抗相比帕博利珠单抗可显著延长无进展生存期（PFS），差异具有统计学意义，且获益在PD-L1表达高和PD-L1表达低的患者中均可见。[3]在EGFR突变NSCLC患者中，双特异性抗体的初步研究“非常有希望”。双特异性抗体（如volrustomig）在较难治疗的PD-L1阴性人群中具有良好的PFS数据。[4]反方：双抗尚难撼动PD-(L)1基石地位Dr. Kalemkerian从不同的角度探讨了这个问题，反驳了一系列他认为“未经证实”的关于双特异性抗体的假设。有人提出“双特异性抗体比联合疗法更好，已有初步数据和生物学原理证实”。他认为这些论点需要澄清，这一问题的关键在于“双特异性免疫靶向治疗是否比免疫检查点抑制剂单药治疗更能改善生存。”Dr. Kalemkerian通过展示一系列不成功的研究（涉及7,000多名患者）反驳了Dr. Riess的演讲。这些研究并未证明在抗PD-1/PD-L1疗法中添加其他免疫检查点抑制剂或血管内皮生长因子（VEGF）靶向药物有益。1.抗PD-(L)1联合抗血管生成Dr. Kalemkerian回顾了联用血管生成靶向药物贝伐珠单抗或多靶点酪氨酸激酶抑制剂（包括仑伐替尼、卡博替尼和司曲替尼）的试验生存数据，以及对比PD-1/VEGF双特异性抗体依沃西单抗和PD-1抗体帕博利珠单抗的HARMONi-2试验数据。Lung-MAP S1800A：在既往接受过抗PD-1/PD-L1治疗的患者中，使用帕博利珠单抗（pembrolizumab）+雷莫芦单抗（ramucirumab）缺乏无进展生存期和缓解率获益，尽管该试验以总生存（OS）为主要终点，且OS获益具有统计学意义。[5]APPLE(WJOG)：该试验发现在化疗中添加抗血管生成贝伐珠单抗没有任何有意义的增益。[6]LEAP-007：结果显示帕博利珠单抗+乐伐替尼（抗血管生成）组合疗效反劣于单药帕博利珠单抗，且毒性更大。[7]SAPPHIRE：这项研究对比了司曲替尼（sitravatinib）+纳武利尤单抗（nivolumab）vs多西他赛单药用于二线治疗，结果显示免疫疗法联合抗血管生成疗法并不能改善结果。[8]HARMONi-2：PD-1/VEGF双特异性抗体依沃西单抗的结果似乎优于PD-1抗体帕博利珠单抗，但对比两个药物的HARMONi-2试验存在需要考量的重要因素，比如III期HARMONi-2缺乏OS数据；帕博利珠单抗单药并不是PD-L1表达1-49%患者真正的标准治疗方法；中位随访时间仍然很短；需等待HARMONi-2研究结果在来自更广泛的地理和种族的患者中得到确认。2.抗PD-(L)1联合抗CTLA-4Dr. Kalemkerian分析了PD-(L)1和抗CTLA-4药物组合的研究结果在非小细胞肺癌和小细胞肺癌中的研究结果。通过从2019~2023年的一系列研究，他发现联合治疗的结果为“无有意义的获益”或“毒性增加”，其中一些研究是双输（lose lose），比如ARCTIC研究。ARCTIC：III期ARCTIC评估了度伐利尤单抗±Tremelimumab对比标准治疗（SoC）三线及以上治疗晚期NSCLC的疗效，根据PD-L1表达情况分为PD-L1 TC≥25％亚组和PD-L1 TC<25％亚组。结果显示PD-L1抑制剂+CTLA-4抑制剂的毒性更大，相比单用度伐利尤单抗无OS获益。[9]CASPIAN：在广泛期小细胞肺癌治疗方面，度伐利尤单抗+Tremelimumab+化疗相比度伐利尤单抗+化疗使毒性发生率增加，OS反而缩短2.5个月（10.4 vs 12.9个月）。[10]目前还有很多失败的ICI联合方案（联合化疗以外的药物），未来还会有更多失败的联合策略出现。那么，双特异性抗体免疫治疗会取代PD-(L)1药物吗？Dr. Kalemkerian的答案是‘不会’，至少现在不会。Dr. Kalemkerian说“至少今天不会”，这与他的辩论对手提出的一个关键概念“时机”相呼应。展望未来我们是根据目前已有研究发现对双特异性抗体做出判断，还是根据未来可能的研究发现做出判断？在演讲中，Dr. Riess着眼于不久的将来，并援引冰球传奇人物Wayne Gretzky的智慧来处理这个问题——滑向冰球将要去的地方，而不是它曾经去过的地方。[11]与之相反，Dr. Kalemkerian秉持"紧盯当下冰球位置"的务实精神，要求业内同道以当前最有效治疗方法为基准来评估新研究数据，在冰球滑向可能错误的角落之前，目光所及之处是正确的冰球。参考文献（上下滑动可查看）1. Parvez A, Choudhary F, Mudgal P, Khan R, Qureshi KA, Farooqi H, Aspatwar A. PD-1 and PD-L1: architects of immune symphony and immunotherapy breakthroughs in cancer treatment. Front Immunol. 2023 Dec 1;14:1296341. doi: 10.3389/fimmu.2023.1296341. PMID: 38106415; PMCID: PMC10722272.2. Zhong T, et al. AACR-NCI-EORTC International Conference 2023. Poster #B123, Abstract #35333, Boston, MA, USA3. Zhou C, Chen J, Wu L, et al: Phase 3 study of ivonescimab (AK112) vs pembrolizumab as first-line treatment for PD-L1–positive advanced NSCLC: Primary analysis of HARMONi-2. 2024 World Conference on Lung Cancer. Abstract PL02.04. Presented September 8, 2024.4. Dovedi SJ, Elder MJ, Yang C, Sitnikova SI, Irving L, Hansen A, Hair J, Jones DC, Hasani S, Wang B, Im SA, Tran B, Subramaniam DS, Gainer SD, Vashisht K, Lewis A, Jin X, Kentner S, Mulgrew K, Wang Y, Overstreet MG, Dodgson J, Wu Y, Palazon A, Morrow M, Rainey GJ, Browne GJ, Neal F, Murray TV, Toloczko AD, Dall’Acqua W, Achour I, Freeman DJ, Wilkinson RW, Mazor Y. Design and Efficacy of a Monovalent Bispecific PD-1/CTLA4 Antibody That Enhances CTLA4 Blockade on PD-1+?Activated T Cells. Cancer Discov. 2021 May;11(5):1100-1117. doi: 10.1158/2159-8290.CD-20-1445. Epub 2021 Jan 8. PMID: 33419761.5. Reckamp KL, Redman MW, Dragnev KH, et al. Phase II Randomized Study of Ramucirumab and Pembrolizumab Versus Standard of Care in Advanced Non-Small-Cell Lung Cancer Previously Treated With Immunotherapy-Lung-MAP S1800A [published correction appears in J Clin Oncol. 2022 Sep 1;40(25):3002. doi: 10.1200/JCO.22.01464.].?J Clin Oncol. 2022;40(21):2295-2306. doi:10.1200/JCO.22.009126. Shiraishi Y, Kishimoto J, Tanaka K, Sugawara S, Daga H, Hirano K, Azuma K, Hataji O, Hayashi H, Tachihara M, Mitsudomi T, Seto T, Nakagawa K, Yamamoto N, Okamoto I. Treatment Rationale and Design for APPLE (WJOG11218L): A Multicenter, Open-Label, Randomized Phase 3 Study of Atezolizumab and Platinum/Pemetrexed With or Without Bevacizumab for Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer. Clin Lung Cancer. 2020 Sep;21(5):472-476. doi: 10.1016/j.cllc.2020.03.010. Epub 2020 Apr 10. PMID: 32381420.7. Yang, James Chih-Hsin et al. Journal of Thoracic Oncology, Volume 19, Issue 6, 941 – 953 Pembrolizumab With or Without Lenvatinib for First-Line Metastatic NSCLC With Programmed Cell Death-Ligand 1 Tumor Proportion Score of at least 1% (LEAP-007): A Randomized, Double-Blind, Phase 3 Trial8. Borghaei H, de Marinis F, Dumoulin D, Reynolds C, Theelen WSME, Percent I, Gutierrez Calderon V, Johnson ML, Madroszyk-Flandin A, Garon EB, He K, Planchard D, Reck M, Popat S, Herbst RS, Leal TA, Shazer RL, Yan X, Harrigan R, Peters S; SAPPHIRE Investigators. SAPPHIRE: phase III study of sitravatinib plus nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. Ann Oncol. 2024 Jan;35(1):66-76. doi: 10.1016/j.annonc.2023.10.004. Epub 2023 Oct 20. PMID: 37866811.9. Planchard D，et al. ARCTIC: durvalumab with or without tremelimumab as third-line or later treatment of metastatic non-small-cell lung cancer. Ann Oncol. 2020 May;31(5):609-618. doi: 10.1016/j.annonc.2020.02.006. Epub 2020 Feb 20. PMID: 32201234.10. Paz-Ares L, et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN. ESMO Open. 2022 Apr;7(2):100408. doi: 10.1016/j.esmoop.2022.100408. Epub 2022 Mar 10. PMID: 35279527; PMCID: PMC9161394.11. A common misattribution of a quote that may have come from Wayne Gretzky’s father（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。

免疫疗法临床结果临床3期上市批准上市后研究

2025-04-08

·癌度

让人惊叹，高TMB晚期小细胞肺癌两次治疗失败后单用PD-1肿瘤病灶全消失18个月之久！

癌度医学临床招募资讯微信群（点击）今天癌度通过一个刊登的小细胞肺癌治疗案例，通过患者的治疗线数和用药、疗效情况来讨论下，为何有的时候治疗效果很好。这里面运气的成分占到了多大的成分。相关的疗效预测指标起到了什么作用？1、小细胞肺癌以及PD-1治疗角色小细胞肺癌（SCLC）是一种高度侵袭性的肺癌亚型，大概占所有肺癌的15%，尽管最初对放疗和化疗敏感，但是很多患者会在治疗1年内复发，导致预后不良。尽管免疫检查点抑制剂联合传统的化疗和放疗延长了患者生存期，但是仅仅延长了中位总生存时间2.2个月至2.4个月左右，这肯定与患者花费高额治疗费用所期望的是不一样的，因此需要急迫理解什么样的患者能从免疫治疗里受益。根据一些早期临床试验，2019年6月，PD-1抑制剂帕博利珠单抗在美国获批用于治疗有铂类化疗史的高肿瘤突变负荷（TMB）的广泛期小细胞肺癌，这些患者必须是经过了两种系统治疗以后且病情进展，也就是属于三线以后的时候才可以使用的药物，相应的结果表明仅仅延长了中位无进展生存时间2个月，延长了中位总生存时间7.7个月，今天给大家介绍的治疗案例是有患者使用该药实现了18个月的长期缓解，原因究竟是什么呢？参考文献刊例示意图2、18个月的长期缓解这是一个65岁的女性患者，确诊的时候就已经发生了广泛性转移，一线治疗使用的是卡铂、依托泊苷和PD-L1抑制剂度伐利尤单抗，给药顺序是：度伐利尤单抗、然后是依托泊苷和卡铂。但是在第一个疗程中，患者接受依托泊苷的时候出现过敏性休克。立即停药后给予西咪替丁、地塞米松和氯苯那敏，以及盐水输注。患者症状得以改善，过敏反应没有复发。确诊病情时患者已经发生了广泛转移由于出现了不良反应，所以患者治疗改为使用顺铂联合伊立替康，经过4个疗程之后，肺部和乳房肿块均减少，使用FoundationOne基因检测套餐对肿瘤组织样本进行二代基因测序，发现患者为高肿瘤突变负荷，每兆碱基有10个突变，因此可以使用PD-1抑制剂帕博利珠单抗，其他的分子指标：微卫星稳定型，TP53基因突变、PTEN基因突变、RB1基因缺失、SOX2、PIK3CA和FGF12扩增。患者的治疗过程和影像学检查患者开始使用单药PD-1，可评估肿瘤病灶完全消失达到了完全缓解，并维持了18个月以上的时间。开始PD-1治疗一周后，患者双掌和脚掌出现丘疹和脓疱。这被诊断为患者原有的掌跖脓疱病加重。开始使用外用类固醇治疗，症状得到良好控制。3、给我们的启发肿瘤治疗如排兵布阵，如果患者三线治疗使用的是其他的药物，比如抗血管生成靶向药安罗替尼，而不是PD-1，估计是肯定实现不了如此好的效果。而且小细胞肺癌一般不推荐做基因检测，因为小细胞肺癌只有极少数情况会出现EGFR和ALK突变，能找到对应的靶向药。但是如果说要预测三线治疗的PD-1效果，那就是如上面的患者做一种比较大的基因检测套餐，因为这种套餐才能检测到TMB指标，目前来说全网最合适的是7500元测910个基因的套餐。当然也提醒大家量力而为。这里一个很让人费解的问题是一线中免疫治疗药物度伐利尤单抗会起效吗？按说应该是能起效，不过遗憾的是因为依托泊苷的不良反应而未能坚持一线治疗措施。希望本文给到大家一些启发和思考，欢迎大家关注癌度，加入癌度病友社群！参考文献：Kiyohide Komuta, et al., Long-Term Complete Response to Pembrolizumab in Tumor Mutation Burden-High Small Cell Lung Cancer: A Case Report, Case Rep Oncol 2025;18:443–448. 往期推荐吞噬癌细胞，抗CD24人源化单克隆抗体KH801治疗实体瘤，可申请免费用！新概念抗癌药之一，靶向CD46免疫调节抗体偶联药FOR46首次人体临床试验，疗效令人鼓舞！开眼界，IDH1基因突变会发生在肺癌，使用艾伏尼布实现了神奇的逆转！抗癌需要光？所以LS-HB来了，光动力疗法招募多种实体肿瘤免费用，癌魔以“光”灭之！

免疫疗法临床结果

100 项与依托泊苷相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00125	依托泊苷	L01CB01	DB00773

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
膀胱癌	日本	Clinigen Ltd.	1987-04-30
白血病	日本	Clinigen Ltd.	1987-04-30
淋巴瘤	日本	Nippon Kayaku Co., Ltd.	1987-03-31
卵巢癌	日本	Nippon Kayaku Co., Ltd.	1987-03-31
宫颈癌	日本	Nippon Kayaku Co., Ltd.	1987-03-31
小细胞肺癌	美国	Corden Pharma Latina SpA	1983-11-10
睾丸肿瘤	美国	Corden Pharma Latina SpA	1983-11-10

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
铂耐药性卵巢癌	临床3期	中国	江苏恒瑞医药股份有限公司	2019-08-16
原发部位不明恶性肿瘤	临床3期	美国	Pharmacia & Upjohn, Inc.	2003-09-01
原发部位不明恶性肿瘤	临床3期	美国	AstraZeneca PLC	2003-09-01
原发部位不明恶性肿瘤	临床3期	美国	Eli Lilly & Co.	2003-09-01
广泛期小细胞肺癌	临床3期	美国	GSK Plc	2001-04-01
广泛期小细胞肺癌	临床3期	中国	GSK Plc	2001-04-01
广泛期小细胞肺癌	临床3期	奥地利	GSK Plc	2001-04-01
广泛期小细胞肺癌	临床3期	比利时	GSK Plc	2001-04-01
广泛期小细胞肺癌	临床3期	巴西	GSK Plc	2001-04-01
广泛期小细胞肺癌	临床3期	保加利亚	GSK Plc	2001-04-01

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临床结果

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03980925 (GETNE T1913, CTgov)	临床2期	胃肠道神经内分泌肿瘤 \| 胃肠胰神经内分泌肿瘤	37	Nivolumab+Etoposide+Carboplatin	膚憲築選鏇鹽構製積衊 = 襯鑰鏇衊蓋鑰鑰遞簾夢網淵鏇築顧鏇艱壓製網 (積膚構製遞壓鑰鬱觸網, 構選餘觸窪壓襯網廠顧 ~ 醖糧鑰艱衊築觸鹹鏇觸) 更多	-	2025-01-13
NCT02705508 (Pubmed \| Hematology) 人工标引	临床2期	结外NK-T细胞淋巴瘤一线	34	PEG (pegaspargase, etoposide, gemcitabine)	製鹹顧醖蓋憲製蓋醖獵(夢鹽製餘蓋艱糧簾襯遞) = 蓋糧鹹壓鏇築簾鹹淵壓齋膚繭壓襯簾製膚鏇鑰 (積膚醖簾憲齋積糧築廠 ) 更多	积极	2024-12-31
NCT04923776 (CTgov)	临床2期	广泛期小细胞肺癌	2	Stereotactic Body Radiation Therapy (SBRT)+Etoposide+Carboplatin+Atezolizumab	製淵鏇窪衊鹹獵鑰鹽夢(積膚獵製餘選窪蓋衊選) = 齋憲糧積鹽繭膚遞蓋選製齋簾鏇膚夢窪繭網夢 (願鹽夢網繭顧醖廠夢淵, 鑰遞襯遞鹽範鹽憲糧餘 ~ 襯蓋築鑰壓積鏇廠糧繭) 更多	-	2024-12-30
NCT00801216 (SCNSL1, CTgov)	临床2期	中枢神经系统疾病 \| B细胞淋巴瘤	40	etoposide+cyclophosphamide+carmustine+Rituximab+methotrexate+Thiotepa+cytarabine	構願醖製獵鹹積構蓋鬱 = 襯齋鏇積網衊鹹艱鏇簾膚淵築遞網鑰範簾夢齋 (簾獵壓憲鬱憲糧膚築艱, 齋顧繭顧構憲鬱窪夢製 ~ 糧餘鏇淵鏇糧鏇顧蓋製) 更多	-	2024-12-10
ESMO_ASIA2024	N/A	广泛期小细胞肺癌一线	274	Cisplatin (CDDP)+Etoposide (ETP)+Durvalumab (DUR)	觸鑰膚蓋獵齋觸壓廠鑰(膚範衊築窪鏇網夢膚網) = 8% vs. 4% 觸鹽夢觸壓鹽鬱願鹹網 (鹹範蓋艱範蓋夢膚壓膚 ) 更多	积极	2024-12-07
ESMO_ASIA2024	N/A	广泛期小细胞肺癌一线	274	Carboplatin (CBDCA)+ETP+Atezolizumab (ATZ)		积极	2024-12-07
ASH2024	N/A	多发性骨髓瘤	-	Etoposide + G-CSF	鹹簾壓鑰齋範網餘簾鏇(觸鑰廠蓋鹹廠顧鏇鑰鬱) = The primary adverse events were grade III-IV bone marrow suppression (100%) and febrile neutropenia (22.7%), with no documented bloodstream infections or hepatorenal toxicity 壓製壓鏇鑰憲壓選廠製 (鑰願選齋構鹹憲鑰遞廠 )	-	2024-12-07
NCT04951115 (CTgov)	临床2期	小细胞肺癌	6	Stereotactic Body Radiotherapy+Etoposide+Carboplatin+Cisplatin+Durvalumab	範積壓選蓋蓋艱築範鏇 = 鬱築觸鏇顧淵網鬱艱獵選網構繭簾齋膚簾膚餘 (製觸鑰餘製艱糧糧鹹膚, 選齋壓鑰選鬱範鹹淵範 ~ 簾醖鏇淵餘遞鏇繭壓鬱) 更多	-	2024-11-26
NCT03923179 (ESMO2024) 人工标引	临床2期	HER2阳性转移性乳腺癌 HER2 Positive	22	Pyrotinib 400mg per dayetoposide	鹽膚選壓願齋醖範鹹遞(衊衊鏇遞鑰淵網觸構積) = 艱簾蓋蓋鹹顧憲網鹹範鏇廠構壓積衊廠淵範築 (顧蓋製選構鏇襯範蓋鏇, 7.6 ~ 10.4) 更多	积极	2024-09-16
ESMO2024 人工标引	N/A	弥漫性大B细胞淋巴瘤 G6PD deficiency	82	RituximabCyclophosphamideDoxorubicin HydrochlorideVincristine SulfatePrednisone	範觸繭夢夢餘憲願餘夢(築淵淵淵願糧鹽簾遞製) = 鏇鏇鏇範鑰餘獵鏇壓製蓋鬱製鹹範艱糧壓構膚 (繭遞鬱衊餘窪遞遞鬱壓 ) 更多	不佳	2024-09-15
ESMO2024 人工标引	N/A	弥漫性大B细胞淋巴瘤 G6PD deficiency	82	RituximabCyclophosphamideEtoposideVincristine SulfatePrednisone	範觸繭夢夢餘憲願餘夢(築淵淵淵願糧鹽簾遞製) = 積蓋襯鹽醖鏇窪壓鹹範蓋鬱製鹹範艱糧壓構膚 (繭遞鬱衊餘窪遞遞鬱壓 ) 更多	不佳	2024-09-15
JPRN-jRCTs031180216 (JCOG1205/1206, ESMO2024) 人工标引	临床3期	肺神经内分泌肿瘤	221	Etoposide/cisplatin (EP)	廠遞觸鑰製齋憲淵窪衊(夢遞構願顧淵簾築醖膚) = 夢鹹網襯醖網艱築齋範繭鬱築鏇憲窪顧鹽製築 (範製醖鏇膚膚範餘築襯 ) 更多	不佳	2024-09-14
JPRN-jRCTs031180216 (JCOG1205/1206, ESMO2024) 人工标引	临床3期	肺神经内分泌肿瘤	221	Irinotecan/cisplatin (IP)	廠遞觸鑰製齋憲淵窪衊(夢遞構願顧淵簾築醖膚) = 糧遞觸蓋選窪積窪衊膚繭鬱築鏇憲窪顧鹽製築 (範製醖鏇膚膚範餘築襯 ) 更多	不佳	2024-09-14