Tan Zhichao, Wu Yan, Fan Zhengfu, Gao Tian, Guo Wei, Bai Chujie, Xue Ruifeng, Li Shu, Zhang Lu, Wang Xinyu, Jia Ling, Liu Jiayong
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Bone and Soft Tissue Tumor, Peking University Cancer Hospital and Institute, Beijing, China.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital and Institute, Beijing, China.
Clin Cancer Res. 2024 Dec 16;30(24):5577-5583. doi: 10.1158/1078-0432.CCR-24-2444.
Alveolar soft part sarcoma (ASPS) is an ultrarare soft-tissue sarcoma with a high rate of metastasis and no established treatment. This study aimed to explore the efficacy and safety of anlotinib (a tyrosine kinase inhibitor) and TQB2450 (a PD-L1 inhibitor) in patients with ASPS.
This single-arm, phase II study evaluated the efficacy of TQB2450, an anti-PD-L1 agent, combined with anlotinib, a tyrosine kinase inhibitor, in adults with advanced ASPS. TQB2450 was given intravenously (1,200 mg) on day 1, and anlotinib (12 mg/day) was taken orally from day 1 to 14 every 3 weeks. The primary endpoint was overall response rate, with secondary endpoints including duration of response, progression-free survival, and overall survival. Lymphocyte infiltration and tertiary lymphoid structure (TLS) were also analyzed as potential prognostic biomarkers.
The study enrolled 29 patients, of whom 28 were evaluable (one withdrew because of acute pancreatitis). An objective response was achieved in 82.1% of patients, including 4 complete and 19 partial responses. The median time to response was 2.8 months, and the duration of response was not reached, with an estimated median progression-free survival of 35.2 months. Grade 3 to 4 treatment-related adverse events occurred in 44.8% of patients, with no study-related deaths. Responders had a higher proportion of TLS area, TLS density, and CD20-positive immune cells.
The combination of anlotinib and TQB2450 is effective and tolerable in patients with ASPS. TLS may serve as a prognostic biomarker, meriting further investigation.
肺泡软组织肉瘤（ASPS）是一种极为罕见的软组织肉瘤，转移率高且尚无既定治疗方法。本研究旨在探讨安罗替尼（一种酪氨酸激酶抑制剂）和TQB2450（一种程序性死亡受体配体1（PD-L1）抑制剂）在ASPS患者中的疗效和安全性。
这项单臂II期研究评估了抗PD-L1药物TQB2450联合酪氨酸激酶抑制剂安罗替尼在晚期ASPS成人患者中的疗效。TQB2450于第1天静脉注射（1200毫克），安罗替尼（12毫克/天）从第1天至第14天每3周口服一次。主要终点为总缓解率，次要终点包括缓解持续时间、无进展生存期和总生存期。淋巴细胞浸润和三级淋巴结构（TLS）也作为潜在的预后生物标志物进行了分析。
该研究纳入了29例患者，其中28例可评估（1例因急性胰腺炎退出）。82.1%的患者获得了客观缓解，包括4例完全缓解和19例部分缓解。中位缓解时间为2.8个月，缓解持续时间未达到，估计中位无进展生存期为35.2个月。44.8%的患者发生了3至4级治疗相关不良事件，无研究相关死亡。缓解者的TLS面积、TLS密度和CD20阳性免疫细胞比例更高。
安罗替尼和TQB2450联合应用于ASPS患者有效且耐受性良好。TLS可能作为一种预后生物标志物，值得进一步研究。
