Background:Peptide Receptor Radionuclide Therapy (PRRT), a form of Radioligand Therapy (RLT), and Capecitabine/Temozolomide (CAPTEM) are cornerstones of systemic therapy for metastatic pancreatic neuroendocrine tumors (PNETs). Data regarding comparative efficacy are lacking. Herein, we compare the efficacy of PRRT vs. CAPTEM as second-line/beyond regimens and treatment sequencing.Methods:Clinicopathologic, radiographic, and genomic data were captured for metastatic PNETs seen in our multi-disciplinary NET clinic between 2013 and 2023. The primary outcome was progression-free survival (PFS) after progression on a previous line of systemic therapy. The secondary outcomes were objective response rate (ORR), time to response (TTR), and overall survival (OS).Results:Fifty-nine cases were included. PFS was similar in the PRRT (n= 29) and CAPTEM (n= 30) groups (PRRT = 21.90 months vs. CAPTEM = 20.03 months; HR 0.99;p= 0.97). On subgroup analysis, PRRT had longer PFS in cases without extrahepatic metastases (26.47 months vs. 17.67 months;p= 0.03) and cases with a mutation in the MEN1, DAXX, and/or ATRX genes (28.43 months vs. 18.67 months;p= 0.03). PRRT had reduced PFS in patients with grade 3 disease (7.83 months vs. 16.33 months;p= 0.02). ORR did not vary significantly (34.78% vs. 40.91%;p= 0.67). CAPTEM responders showed shorter TTR (6.03 months vs. 11.15 months;p= 0.03). In patients who received both, OS did not vary based on the sequence (HR 1.20;p= 0.75).Conclusions:PFS, ORR, and OS are similar when using PRRT vs. CAPTEM as second-line-and-beyond therapy for patients with metastatic PNETs. However, patients withMEN1,DAXX, and/orATRXmutations or without extrahepatic metastases might better benefit from PRRT and patients with grade 3 disease from CAPTEM. Candidates for surgical debulking or with tumor-induced symptoms may benefit from initial treatment with CAPTEM due to shorter TTR.
背景：肽受体放射性核素治疗（PRRT）作为放射性配体疗法（RLT）的一种形式，以及卡培他滨/替莫唑胺（CAPTEM）方案，是转移性胰腺神经内分泌肿瘤（PNETs）系统性治疗的基石。目前尚缺乏关于两者疗效比较的数据。本研究旨在比较PRRT与CAPTEM作为二线及以上治疗方案及其治疗顺序的疗效。 方法：收集2013年至2023年间在我们多学科神经内分泌肿瘤诊所就诊的转移性PNET患者的临床病理、影像学和基因组学数据。主要研究终点为既往一线系统性治疗进展后的无进展生存期（PFS）。次要研究终点包括客观缓解率（ORR）、至缓解时间（TTR）和总生存期（OS）。 结果：共纳入59例病例。PRRT组（n=29）与CAPTEM组（n=30）的PFS相似（PRRT = 21.90个月 vs. CAPTEM = 20.03个月；HR 0.99；p=0.97）。亚组分析显示，在无肝外转移的病例中（26.47个月 vs. 17.67个月；p=0.03）以及存在MEN1、DAXX和/或ATRX基因突变的病例中（28.43个月 vs. 18.67个月；p=0.03），PRRT组的PFS更长。在3级疾病患者中，PRRT组的PFS较短（7.83个月 vs. 16.33个月；p=0.02）。两组ORR无显著差异（34.78% vs. 40.91%；p=0.67）。CAPTEM组缓解者的TTR更短（6.03个月 vs. 11.15个月；p=0.03）。在接受两种治疗的患者中，OS不因治疗顺序不同而有差异（HR 1.20；p=0.75）。 结论：对于转移性PNET患者，将PRRT与CAPTEM作为二线及以上治疗时，其PFS、ORR和OS相似。然而，携带MEN1、DAXX和/或ATRX基因突变或无肝外转移的患者可能从PRRT中获益更多，而3级疾病患者可能更适合CAPTEM。对于适合手术减瘤或存在肿瘤相关症状的患者，由于CAPTEM的TTR更短，初始采用CAPTEM治疗可能使其获益。
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