近日，首都医科大学北京积水潭医院牛晓辉团队研究了匹米替尼与安慰剂治疗腱膜巨细胞瘤的疗效与安全性。2026年3月5日出版的《柳叶刀》杂志发表了这项成果。

腱鞘巨细胞瘤是一种罕见的、具有局部侵袭性的肿瘤，好发于其他方面健康的成年人。目前全身性治疗方案有限，存在着未满足的临床需求。研究组报告了MANEUVER试验第一部分的结果，该部分旨在评估匹米替尼（一种高选择性、强效的集落刺激因子-1受体抑制剂）在TGCT患者中的疗效和安全性。

MANEUVER是一项在亚洲、欧洲和北美的40家专科医院进行的随机、安慰剂对照、III期研究。年龄≥18岁、不可切除且有症状的TGCT患者（患者报告的最严重僵硬或最严重疼痛评分在0-10分量表上≥4分）被随机分配（2:1，双盲）至口服匹米替尼50 mg每日一次组或安慰剂组，治疗24周（第一部分）。独立的统计学家使用中心交互式网络应答系统生成随机化方案；分层因素为地区（中国 vs 非中国）。通过使用外观与匹米替尼相同的安慰剂实现设盲。

在第一部分中，患者、所有研究者和研究资助者对治疗分配均保持设盲。所有完成第一部分的患者均可继续进入开放标签的第二部分：匹米替尼组患者可继续接受相同剂量，安慰剂组患者可交叉接受匹米替尼治疗24周。完成第二部分且符合条件的患者可进入第三部分，长期继续每日一次匹米替尼治疗。主要终点是意向治疗人群（所有随机分配的患者）中，至第25周时由盲态独立审查委员会根据实体瘤疗效评价标准1.1版评估的客观缓解率。安全性分析在至少接受过一次研究药物剂量的患者中进行。缺失数据未进行填补，仅分析观察到的数据。试验入组已完成；研究已在ClinicalTrials.gov注册（NCT05804045）且正在进行中。

在2023年4月27日至2024年3月29日期间，共筛选126例患者，其中94例患者（中国45例，非中国49例）被随机分配并接受了匹米替尼（63例）或安慰剂（31例）治疗。30例（32%）患者为男性，64例（68%）为女性。第25周时，匹米替尼组的客观缓解率为54%（63例中的34例），安慰剂组为3%（31例中的1例）（绝对差异51% [95% CI 33–63]，p<0.0001）。匹米替尼主要与轻度的治疗期出现的不良事件相关，主要包括多数可控的无症状实验室检查异常和临床事件，如瘙痒、面部水肿、皮疹、眼周水肿和疲劳。在匹米替尼治疗组患者中，发生率超过10%的仅有的3级或4级治疗期出现的不良事件是血肌酸磷酸激酶升高，发生在63例患者中的8例（13%）。安慰剂组最常见的治疗期出现的不良事件是疲劳和关节痛。匹米替尼治疗组63例患者中有5例（8%）发生了剂量下调，63例中有1例（2%）停止了治疗。未见胆汁淤积性肝毒性、药物性肝损伤或皮肤毛发色素减退。

研究结果表明，匹米替尼显示出强劲的抗肿瘤活性，并在与TGCT相关的功能受限和症状负担方面带来了有临床意义的改善，为这一亟待满足的临床需求提供了有效的治疗选择，且其安全性可控。

附：英文原文

Title: Pimicotinib versus placebo for tenosynovial giant cell tumour (MANEUVER): an international, randomised, placebo-controlled, phase 3 trial

Author: Hairong Xu, Xiaohui Niu, Vinod Ravi, Javier Martin-Broto, Albiruni Abdul Razak, Ramy Saleh, Yong Zhou, Jingnan Shen, Tang Liu, Kamlesh Kumar Sankhala, César Serrano, Silvia Stacchiotti, Jing Wang, Giacomo G Baldi, Yi Feng, Yingqi Hua, Tao Li, Piotr Rutkowski, Xiaojing Zhang, Gabriel Tinoco, Qingping Zou, Boyao Shan, Xiangyu Zhu, Hans Gelderblom

Issue&Volume: 2026-03-05

Abstract:

Background

Tenosynovial giant cell tumour (TGCT) is a rare, locally aggressive neoplasm that affects otherwise healthy adults. There are few systemic treatment options, highlighting an unmet need. We report the results of part 1 of the MANEUVER trial, which aimed to evaluate the efficacy and safety of pimicotinib, a highly selective, potent, colony-stimulating factor-1 receptor inhibitor, in patients with TGCT.

Methods

MANEUVER is a randomised, placebo-controlled, phase 3 study done in 40 specialised hospitals in Asia, Europe, and North America. Patients aged 18 years and older with unresectable, symptomatic TGCT (patient-reported worse stiffness or worst pain of at least 4 on a scale of 0–10) were randomly assigned (2:1, double-blind) to oral, once-daily pimicotinib 50 mg or placebo for 24 weeks (part 1). An independent statistician used a central interactive web response system to generate the randomisation schedule; stratification was by region (China vs non-China). Masking was achieved by using placebo identical in appearance to pimicotinib. In part 1, patients, all investigators, and study funders were masked to treatment assignments. All patients who completed part 1 were allowed to continue to open-label part 2: pimicotinib-treated patients could continue the same dosage and placebo-treated patients could cross over to receive pimicotinib for 24 weeks. Eligible patients who completed part 2 were allowed to continue once-daily pimicotinib long-term in part 3. The primary endpoint was objective response rate (ORR) at week 25 by blinded independent review committee per Response Evaluation Criteria in Solid Tumors version 1.1 in the intention-to-treat population (all randomised patients). Safety was analysed in patients who received at least one dose of study drug. Missing data were not imputed and only observed data were analysed. Trial enrolment is complete; the study is registered at ClinicalTrials.gov (NCT05804045) and is ongoing.

Findings

Between April 27, 2023, and March 29, 2024, 126 patients were screened and 94 patients (China [n=45], non-China [n=49]) were randomly assigned to, and received, pimicotinib (n=63) or placebo (n=31). 30 (32%) patients were male and 64 (68%) were female. ORR at week 25 was 54% (34 of 63) in the pimicotinib group and 3% (one of 31) in the placebo group (absolute difference 51% [95% CI 33–63], p<0·0001). Pimicotinib was associated with mainly mild treatment-emergent adverse events, including mostly manageable asymptomatic laboratory abnormalities and clinical events, such as pruritus, facial oedema, rash, periorbital oedema, and fatigue. The only grade 3 or 4 treatment-emergent adverse event occurring in more than 10% of pimicotinib-treated patients was increase in blood creatine phosphokinase, in eight (13%) of 63 patients. The most common treatment-emergent adverse events in the placebo group were fatigue and arthralgia. Dose reductions occurred in five (8%) of 63 pimicotinib-treated patients and treatment discontinuations in one (2%) of 63 pimicotinib-treated patients. There was no cholestatic hepatotoxicity, drug-induced liver injury, or hypopigmentation of skin or hair.

Interpretation

Pimicotinib showed robust antitumour activity with clinically meaningful improvements in TGCT-related functional limitations and symptom burden, offering an effective treatment option with a manageable safety profile for this underserved condition.

DOI: 10.1016/S0140-6736(25)02602-9

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)02602-9/abstract