Department of Gastroenterology and Hepatology, Yokohama City University, Japan.
Department of Gastroenterology, Aichi Cancer Center, Japan.
Intern Med. 2023 Jan 15;62(2):159-167. doi: 10.2169/internalmedicine.9416-22. Epub 2022 Jun 14.
Objective The effectiveness of everolimus for the management of pancreatic neuroendocrine neoplasms (PNENs), including the G3/NEC types, remains unclear. We therefore investigated the effectiveness of the drug for the management of PNENs. Methods We analyzed the progression-free survival (PFS) and overall survival (OS) associated with everolimus and factors influencing the PFS and OS. Results One hundred patients were evaluated. The PFS associated with the G1/G2 types tended to be significantly longer than that associated with the G3/NEC types [hazard ratio (HR), 0.45; p=0.005]. A multivariate analysis showed that the significant factors influencing the PFS were age (<65 years old; HR, 0.44; p=0.002), grade (G1/G2; HR, 0.42; p=0.006), everolimus treatment line (≤2nd; HR, 0.55; p=0.031), and presence of treatment with metformin (yes; HR, 0.29; p=0.044). The median OS was 63.8 months. In the multivariate analysis, the significant factors influencing the OS were grade (G1/G2; HR, 0.21; p<0.001), volume of liver metastasis (≤25%; HR, 0.27; p<0.001), everolimus treatment line (≤2nd; HR, 0.27; p<0.001), and presence of primary tumor resection (yes; HR, 0.33; p=0.005). Conclusion The effectiveness of everolimus in the management of G3/NEC types and prognoses tended to be poorer than those associated with the G1/G2 types. Everolimus combined with metformin and early-line treatment with everolimus may be effective for managing advanced PNENs.
目的 依维莫司治疗胰腺神经内分泌肿瘤（PNENs），包括 G3/NEC 型的疗效尚不清楚。因此，我们研究了该药治疗 PNENs 的疗效。
方法 我们分析了依维莫司与无进展生存期（PFS）和总生存期（OS）的关系，以及影响 PFS 和 OS 的因素。
结果 共评估了 100 例患者。G1/G2 型的 PFS 与 G3/NEC 型相比，倾向于显著延长[风险比（HR），0.45；p=0.005]。多因素分析显示，影响 PFS 的显著因素为年龄（<65 岁；HR，0.44；p=0.002）、分级（G1/G2；HR，0.42；p=0.006）、依维莫司治疗线（≤2 线；HR，0.55；p=0.031）和二甲双胍治疗（是；HR，0.29；p=0.044）。中位 OS 为 63.8 个月。在多因素分析中，影响 OS 的显著因素为分级（G1/G2；HR，0.21；p<0.001）、肝转移瘤体积（≤25%；HR，0.27；p<0.001）、依维莫司治疗线（≤2 线；HR，0.27；p<0.001）和原发肿瘤切除术（是；HR，0.33；p=0.005）。
结论 依维莫司治疗 G3/NEC 型和预后的疗效倾向于比 G1/G2 型差。依维莫司联合二甲双胍和早期使用依维莫司可能对治疗晚期 PNENs 有效。
