Abstract：
Everolimus and peptide receptor radionuclide therapy (PRRT, 177Lu-DOTATATE) are 2 treatments recommended in guidelines for gastroenteropancreatic metastatic neuroendocrine tumors. However, the best treatment sequence remains unknown. Methods: We designed a retrospective multicenter study that included patients from the national prospective database of the Groupe d\'Étude des Tumeurs Endocrines who had been treated using everolimus and PRRT between April 2004 and October 2022. The primary aim was to compare the 2 treatments (everolimus and PRRT) in terms of efficacy and safety, and the secondary aim was to evaluate the sequences (PRRT followed by everolimus or everolimus followed by PRRT) based on overall progression-free survival (PFS) (PFS during first treatment + PFS during second treatment) in patients with metastatic neuroendocrine tumors. Results: Both treatments were used for 84 patients. The objective response rate and median PFS were 5 (6.0%) and 16.1 mo (95% CI, 11.5-20.7 mo), respectively, under everolimus and 19 (22.6%) and 24.5 mo (95% CI, 17.7-31.3 mo), respectively, for PRRT. The safety profile was also better for PRRT. Median overall PFS was 43.2 mo (95% CI, 33.7-52.7 mo) for the everolimus-PRRT sequence and 30.6 mo (95% CI, 17.8-43.4 mo) for the PRRT-everolimus sequence (hazard ratio, 0.69; 95% CI, 0.39-1.24; P = 0.22). Conclusion: PRRT was more effective and less toxic than everolimus. Overall PFS was similar between the 2 sequences, suggesting case-by-case discussion if the patient is eligible for both treatments, but PRRT should be used first when an objective response is needed or in frail populations.
摘要：
依维莫司和肽受体放射性核素治疗（PRRT，177Lu-DOTATATE）是胃肠胰腺转移性神经内分泌肿瘤指南中推荐的2种治疗方法。然而,最佳治疗顺序仍然未知。方法：我们设计了一项回顾性多中心研究，纳入了2004年4月至2022年10月期间使用依维莫司和PRRT治疗的患者。主要目的是比较两种治疗方法（依维莫司和PRRT）的疗效和安全性，次要目的是根据转移性神经内分泌肿瘤患者的总体无进展生存期(PFS)(第一次治疗期间的PFS+第二次治疗期间的PFS)评估序列(PRRT后依维莫司或依维莫司后PRRT).结果：两种治疗方法均用于84例患者。客观缓解率和中位PFS分别为5mo（6.0％）和16.1mo（95％CI，11.5-20.7mo），分别,依维莫司和19个月（22.6%）和24.5个月（95%CI，17.7-31.3个月），分别,对于PRRT。PRRT的安全性也更好。依维莫司-PRRT序列的总PFS中位数为43.2mo（95％CI，33.7-52.7mo），PRRT-依维莫司序列的总PFS中位数为30.6mo（95％CI，17.8-43.4mo）（风险比，0.69；95%CI，0.39-1.24；P=0.22）。结论：PRRT比依维莫司更有效，毒性更小。2个序列之间的总体PFS相似，如果患者符合两种治疗的条件，建议逐案讨论，但当需要客观反应或虚弱人群时，应首先使用PRRT。
