Sintilimab Plus Axitinib for Advanced Fumarate Hydratase-Deficient Renal Cell Carcinoma: A Phase 2 Nonrandomized Clinical Trial.

IF 20.1 1区医学 Q1 ONCOLOGY

JAMA Oncology Pub Date : 2025-08-14 DOI:10.1001/jamaoncol.2025.2497

Xingming Zhang,Haoyang Liu,Jiayu Liang,Junjie Zhao,Yongquan Wang,Yuntian Chen,Deying Kang,Qian Chen,Yaowen Zhang,Xiaoxue Yin,Yuhao Zeng,Zilin Wang,Xinan Sheng,Xin Yao,Kan Gong,Xiaodong Liu,Zhibin Chen,Mingxing Qiu,Wei Chen,Zongping Wang,Guangheng Luo,Tingting Zhou,Nanshan Yang,Xiuyi Pan,Ling Nie,Mengni Zhang,Junru Chen,Jinge Zhao,Xu Hu,Lijing Xu,Bo Tang,Jindong Dai,Haolin Liu,Yuchao Ni,Rui Huang,Qiang Wei,Xiang Li,Qiying He,Jiyan Liu,Pengfei Shen,Ni Chen,Zhenhua Liu,Guangxi Sun,Jin Yao,Hao Zeng

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引用次数: 0

Abstract

Importance Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a lethal kidney cancer that has limited therapeutic options. Objective To evaluate the efficacy and safety of sintilimab plus axitinib for treatment of advanced FH-deficient RCC. Design, Setting, and Participants This phase 2 multicenter, open-label, single-arm nonrandomized clinical trial enrolled patients with pathologically confirmed, treatment-naive, advanced FH-deficient RCC and an Eastern Cooperative Oncology Group Performance Status of 0 to 2 from July 1, 2021, to August 29, 2023, across 8 institutions in China. The data cutoff date was December 1, 2024. Intervention Patients received sintilimab, 200 mg, intravenously every 3 weeks, combined with axitinib, 5 mg, orally twice daily, until disease progression, intolerable toxic effects, or withdrawal of consent. Main Outcomes and Measures The primary end points were objective response rate (ORR) via Response Evaluation Criteria in Solid Tumors, version 1.1, and progression-free survival (PFS). Secondary end points included safety, overall survival, disease control rate (proportion of patients with complete or partial response or stable disease for ≥6 months), duration of response, and exploratory genomic-associated outcomes. Results Of 52 patients screened for eligibility, 41 patients (median [range] age, 36 [18-75] years; 10 [24%] female) were enrolled. The median (range) duration of follow-up was 26.0 (0.7-41.6) months. Overall, ORR was 56% (23 patients; 95% CI, 40%-72%), with a median duration of response of not reached (NR; 95% CI, 23.3 months to NR). The disease control rate was 73% (30 patients). The median PFS was 19.8 months (95% CI, 10.9 months to NR). Patients with low somatic copy number alteration burden showed more favorable therapeutic outcomes. Thirteen patients (32%) experienced grade 3 or higher treatment-related adverse events, with the most frequent being hypertriglyceridemia in 3 (7%), rash in 2 (5%), and anemia in 2 (5%). Conclusions and Relevance In this nonrandomized clinical trial, the combination of sintilimab and axitinib demonstrated encouraging ORR and PFS with manageable safety profile in patients with FH-deficient RCC. This combination therapy warrants further validation in a randomized clinical trial. Trial Registration ClinicalTrials.gov Identifier: NCT04387500.

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辛替单抗联合阿西替尼治疗晚期富马酸水合酶缺乏的肾细胞癌：一项2期非随机临床试验。

富马酸水合酶缺陷型肾细胞癌（fh缺陷型RCC）是一种治疗选择有限的致死性肾癌。目的评价辛替单抗联合阿西替尼治疗晚期fh缺乏的肾细胞癌的疗效和安全性。设计、环境和参与者：该2期多中心、开放标签、单组非随机临床试验于2021年7月1日至2023年8月29日在中国8家机构招募了病理证实、未接受治疗、晚期fh缺陷RCC和东部肿瘤合作组性能状态为0至2的患者。数据截止日期为2024年12月1日。干预：患者接受欣替单抗200mg，静脉注射，每3周一次，联合阿西替尼5mg，口服，每日2次，直到疾病进展，无法忍受的毒性作用，或撤回同意。主要结果和测量主要终点是通过实体瘤反应评价标准1.1版的客观缓解率（ORR）和无进展生存期（PFS）。次要终点包括安全性、总生存期、疾病控制率（完全或部分缓解或疾病稳定≥6个月的患者比例）、缓解持续时间和探索性基因组相关结果。结果52例入选患者中，41例(年龄中位数[范围]36岁[18-75]岁；10例（24%）为女性。中位（范围）随访时间为26.0（0.7-41.6）个月。总体而言，ORR为56%(23例；95% CI, 40%-72%)，中位反应持续时间未达到(NR；95% CI， 23.3个月至NR)。疾病控制率73%（30例）。中位PFS为19.8个月（95% CI， 10.9个月至NR）。体细胞拷贝数改变负担低的患者表现出较好的治疗效果。13例患者（32%）出现3级或以上治疗相关不良事件，最常见的是高甘油三酯血症3例（7%），皮疹2例（5%），贫血2例（5%）。结论和相关性在这项非随机临床试验中，sintilimab和axitinib联合应用在fh缺乏的RCC患者中显示出令人鼓舞的ORR和PFS，并且具有可控的安全性。这种联合治疗需要在一项随机临床试验中进一步验证。临床试验注册号：NCT04387500。

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来源期刊

JAMA Oncology Medicine-Oncology

自引率

1.80%

发文量

423

期刊介绍： JAMA Oncology is an international peer-reviewed journal that serves as the leading publication for scientists, clinicians, and trainees working in the field of oncology. It is part of the JAMA Network, a collection of peer-reviewed medical and specialty publications.