Purpose: We report efficacy and safety of 90Y-labeled FAPI-46 (90Y-FAPI-46-RLT) in patients with advanced sarcoma, pancreatic cancer, and other cancer entities. Experimental Design: Up to four cycles of radioligand therapy (RLT) were offered to patients with (i) progressive metastatic malignancy, (ii) exhaustion of approved therapies, and (iii) high fibroblast activation protein (FAP) expression, defined as SUVmax ≥ 10 in more than 50% of tumor. Primary endpoint was RECIST response after RLT. Secondary endpoints included PET response (PERCIST), overall survival (OS), dosimetry, and safety of FAP-RLT. Results: Among 119 screened patients, 21 (18%) were found eligible [n = 16/3/1/1 sarcoma/pancreatic cancer/prostate/gastric cancer; 38% Eastern Cooperative Oncology Group (ECOG) ≥ 2] and received 47 90Y-FAPI-46-RLT cycles; 16 of 21 (76%) patients underwent repeat RLT. By RECIST, disease control was confirmed in 8 of 21 patients [38%; 8/16 (50%) of evaluable patients). There was one partial response (PR) and seven stable diseases after RLT. Disease control was associated with prolonged OS (P = 0.013). PERCIST response was noted in 8 of 21 patients [38%; 8/15 (53%) of evaluable patients]. Dosimetry was acquired in 19 (90%) patients. Mean absorbed dose was 0.53 Gy/GBq in kidney, 0.04 Gy/GBq in bone marrow, and <0.14 Gy/GBq in liver and lung. Treatment-related grade 3 or 4 adverse events were observed in 8 (38%) patients with thrombocytopenia (n = 6) and anemia (n = 6) being most prevalent. Conclusions: 90Y-FAPI-46-RLT was safe and led to RECIST PR in one case as well as stable disease in about one third of patients with initially progressive sarcomas, pancreatic cancer, and other cancers. Discontinuation after the first cycle and a low rate of PR requires future improvement of FAP-RLT.

中文翻译：

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90Y-FAPI-46 放射性配体治疗晚期肉瘤和其他癌症实体的安全性和有效性

目的：我们报告 90Y 标记的 FAPI-46 (90Y-FAPI-46-RLT) 在晚期肉瘤、胰腺癌和其他癌症实体患者中的疗效和安全性。实验设计：向以下患者提供最多四个周期的放射配体治疗 (RLT)：(i) 进行性转移性恶性肿瘤，(ii) 已用尽批准的治疗方法，以及 (iii) 高成纤维细胞活化蛋白 (FAP) 表达，定义为 SUVmax ≥ 10 占50%以上的肿瘤。主要终点是 RLT 后的 RECIST 反应。次要终点包括 PET 反应 (PERCIST)、总生存期 (OS)、剂量测定和 FAP-RLT 的安全性。结果：在 119 名筛查患者中，21 人 (18%) 被发现符合条件 [n = 16/3/1/1 肉瘤/胰腺癌/前列腺癌/胃癌；38% 东部肿瘤合作组 (ECOG) ≥ 2] 并接受 47 个 90Y-FAPI-46-RLT 周期；21 名患者中有 16 名 (76%) 接受了重复 RLT。根据 RECIST，21 名患者中有 8 名确诊为疾病控制 [38%；8/16 (50%) 可评估患者）。RLT 后有 1 例部分缓解 (PR)，7 例疾病稳定。疾病控制与 OS 延长相关（P = 0.013）。21 名患者中有 8 名出现 PERCIST 缓解 [38%；8/15 (53%) 的可评估患者]。对 19 名 (90%) 患者进行了剂量测定。肾脏中的平均吸收剂量为0.53Gy/GBq，骨髓中的平均吸收剂量为0.04Gy/GBq，肝脏和肺中的平均吸收剂量＜0.14Gy/GBq。在 8 名 (38%) 患者中观察到与治疗相关的 3 级或 4 级不良事件，其中血小板减少症 (n = 6) 和贫血 (n = 6) 最为常见。结论：90Y-FAPI-46-RLT 是安全的，并导致 1 例患者达到 RECIST PR，并且约三分之一的最初进展性肉瘤、胰腺癌和其他癌症患者病情稳定。第一个周期后停药且 PR 率较低，需要未来改进 FAP-RLT。