Anti-PD-1 antibody plus anlotinib vs. anlotinib alone in patients with refractory chondrosarcoma: A multicenter, non-randomized phase 2 FLAIL-C trial.

IF 11.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Med Pub Date : 2025-08-26 DOI:10.1016/j.medj.2025.100809

Binghao Li, Lu Xie, Junbo Liang, Yaling Jiang, Keyi Wang, Yunxia Liu, Nong Lin, Xin Huang, Kuo Zhao, Gentao Fan, Meng Liu, Xiaobo Yan, Hao Qu, Hengyuan Li, Jilong Yang, Guangxin Zhou, Zhaoming Ye

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Abstract

Background: There is no standard systemic therapy for unresectable chondrosarcoma. The purpose of this study is to explore the efficacy of combination therapy with an anti-PD-1 antibody and anlotinib in patients with advanced chondrosarcoma.

Methods: Patients with dedifferentiated or high-grade conventional chondrosarcoma were eligible. Anlotinib was administered at 12 mg orally once a day from day 1 to 14 every 3 weeks in all participants. In the combination treatment arm, patients received an additional anti-PD-1 antibody at 200 mg every 3 weeks. The primary endpoint was the 6-month progression-free survival rate (PFSR). Biomarker analyses for therapeutic effectiveness were conducted.

Findings: 70 patients (32 with dedifferentiated and 38 with conventional chondrosarcoma) were enrolled in the study. After a medium follow-up of 15.6 months, combination treatment showed significantly improved outcomes compared to anlotinib alone in the entire population, with a higher 6-month PFSR (60.0% versus 31.4%). The PFS-event inverse probability weighting adjusted Cox model evaluation also revealed a significant benefit of combination treatment (hazard ratio = 0.14, 95% confidence interval [CI]: 0.07-0.30, p < 0.001). Patients with dedifferentiated chondrosarcoma benefited the most from the combination treatment, with improvements in objective response rate (33.3% versus 9.1%), 6-month PFSR (57.1% versus 9.1%), median PFS (7.0 months versus 3.8 months), and 1-year overall survival rate (42.9% versus 18.2%). Effector memory T cells were significantly associated with treatment response (p < 0.001).

Conclusions: The combination treatment demonstrated promising efficacy in advanced chondrosarcoma, particularly for dedifferentiated cases (ClinicalTrials.gov: NCT05193188).

Funding: This trial was supported by Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

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抗pd -1抗体联合安洛替尼与单用安洛替尼治疗难治性软骨肉瘤：一项多中心、非随机2期flil - c试验

背景：对于不可切除的软骨肉瘤没有标准的全身治疗方法。本研究的目的是探讨抗pd -1抗体联合安洛替尼治疗晚期软骨肉瘤的疗效。方法：去分化或高级别常规软骨肉瘤患者均入选。所有参与者每3周从第1天至第14天口服安洛替尼12mg，每天1次。在联合治疗组，患者每3周额外接受200毫克抗pd -1抗体。主要终点是6个月无进展生存率（PFSR）。对治疗效果进行生物标志物分析。结果：70例患者（32例去分化软骨肉瘤，38例常规软骨肉瘤）入组研究。在15.6个月的中期随访后，联合治疗在整个人群中显示出与单独使用anlotinib相比显着改善的结果，具有更高的6个月PFSR（60.0%对31.4%）。pfs -事件逆概率加权校正Cox模型评价也显示联合治疗显著获益（风险比= 0.14,95%可信区间[CI]: 0.07-0.30, p < 0.001）。去分化软骨肉瘤患者从联合治疗中获益最多，客观缓解率（33.3%对9.1%）、6个月PFSR（57.1%对9.1%）、中位PFS（7.0个月对3.8个月）和1年总生存率（42.9%对18.2%）均有改善。效应记忆T细胞与治疗反应显著相关（p < 0.001）。结论：联合治疗在晚期软骨肉瘤，特别是去分化病例中显示出有希望的疗效（ClinicalTrials.gov: NCT05193188）。经费：本试验由正大天庆药业集团有限公司资助。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

期刊介绍： Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.