Department of Nuclear Medicine, West German Cancer Center, University of Duisburg-Essen, Essen, Germany.
German Cancer Consortium (DKTK), Partner Site University Hospital Essen, and German Cancer Research Center (DKFZ), Essen, Germany.
Clin Cancer Res. 2022 Oct 3;28(19):4346-4353. doi: 10.1158/1078-0432.CCR-22-1432.
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.
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.
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.
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.
我们报告了 90Y 标记的 FAPI-46（90Y-FAPI-46-RLT）在晚期肉瘤、胰腺癌和其他癌症患者中的疗效和安全性。
为符合以下条件的患者提供多达四个周期的放射性配体治疗（RLT）：（i）进展性转移性恶性肿瘤，（ii）已用尽批准的治疗方法，（iii）成纤维细胞激活蛋白（FAP）表达高，定义为超过 50%的肿瘤中 SUVmax≥10。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）、剂量学和 FAP-RLT 的安全性。
在 119 名筛选的患者中，有 21 名（18%）被确定符合条件[肉瘤/胰腺癌/前列腺癌/胃癌，n=16/3/1/1；38%的东部合作肿瘤学组（ECOG）≥2]，并接受了 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（38%；16 名可评估患者中的 8 名[50%]）确认疾病得到控制。RLT 后有 1 例部分缓解（PR）和 7 例稳定疾病。疾病控制与延长 OS 相关（P=0.013）。21 名患者中有 8 名（38%；15 名可评估患者中的 8 名[53%]）出现 PERCIST 反应。19 名（90%）患者进行了剂量学检查。肾脏的平均吸收剂量为 0.53Gy/GBq，骨髓为 0.04Gy/GBq，肝脏和肺为<0.14Gy/GBq。8 名（38%）患者发生了 3 级或 4 级与治疗相关的不良事件，血小板减少症（n=6）和贫血症（n=6）最为常见。
90Y-FAPI-46-RLT 是安全的，在最初进展的肉瘤、胰腺癌和其他癌症患者中，有一例导致 RECIST PR，约三分之一的患者出现稳定疾病。第一个周期后停药和 PR 率低需要进一步改进 FAP-RLT。
