神经内分泌癌（NEC）的预后很差。在铂类一线治疗失败后，目前尚无标准的二线治疗被认可。 FOLFIRI 和 CAPTEM 方案在初步研究中显示出有希望的活性。我们的目的是在转移性 NEC 患者中评估这些方案。这是一项开放标签、多中心、随机非比较性 II 期试验，旨在评估 FOLFIRI 或 CAPTEM 在转移性 NEC 患者中的活性和安全性。主要终点是研究者根据 RECIST v1.1 评估得出的 12 周疾病控制率 (12w-DCR) 和根据 CTCAE v5.0 的安全性。其他终点包括总体缓解率（ORR）、无进展生存期（PFS）和总体生存期（OS）。对患者的血清样本进行 NGS miRNome 分析，与健康供体进行比较，以揭示差异表达的 miRNA 作为候选循环生物标志物。该研究因中期分析无效而停止，因为 25 名患者中的 10 名需要最低 12w-DCR 阈值。第一步没有达到。从2017年3月6日至2021年1月18日，112名患者中有53名患者入组。中位随访时间为 22.6 个月（范围：1.4-60.4）。 FOLFIRI 组的 12w-DCR 为 39.1%，CAPTEM 组的 12w-DCR 为 28.0%。在 FOLFIRI 亚组中，12 个月 OS 率为 28.4%（95% CI：12.7-46.5），而在 CAPTEM 亚组中，12 个月 OS 率为 32.4%（95% CI：14.9-51.3）。 FOLFIRI 最常见的 G3-G4 副作用是中性粒细胞减少症 (n = 5, 18.5%) 和贫血 (n = 2, 7.4%)，G3-G4 血小板减少症 (n = 2, 8.0%)、G4 恶心/呕吐 (n = 2, 8.0%) = 1, 4.0%) 对于 CAPTEM。三种 microRNA 成为 NEC 独立预测因子。研究发现高表达值与 PFS 和 OS 降低显着相关。FOLFIRI 和 CAPTEM 的安全性是可控的。 FOLFIRI 和 CAPTEM 化疗在依托泊苷/铂治疗进展后的二线治疗中表现出相当的活性。NCT03387592。版权所有 © 2024。由 Elsevier Ltd 出版。

Neuroendocrine Carcinomas (NECs) prognosis is poor.No standard second-line therapy is currently recognized after failure of platinum-based first-line treatment. FOLFIRI and CAPTEM regimens have shown promising activity in preliminary studies. We aimed to evaluate these regimens in metastatic NEC patients.This is an open-label, multicenter, randomized non-comparative phase II trial to evaluate the activity and safety of FOLFIRI or CAPTEM in metastatic NEC patients. Primary endpoints were the 12 weeks-Disease Control Rate (12w-DCR) by investigator assessment per RECIST v1.1 and safety per CTCAE v5.0. Additional endpoints included overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). Patients' serum samples were subject to NGS miRNome profiling in comparison with healthy donors to reveal differentially expressed miRNAs as candidate circulating biomarkers.The study was halted for futility at interim analysis, as the minimum 12w-DCR threshold of 10 out of 25 patients required for the first step was not reached. From 06/03/2017 to 18/01/2021, 53 out of 112 patients were enrolled. Median follow-up was 22.6 months (range: 1.4-60.4). The 12w-DCR was 39.1 % in the FOLFIRI arm and 28.0 % in the CAPTEM arm. In the FOLFIRI subgroup the 12-months OS rate was 28.4 % (95 % CI: 12.7-46.5) while in the CAPTEM subgroup it was 32.4 % (95 % CI: 14.9-51.3). The most common G3-G4 side effects were neutropenia (n = 5, 18.5 %) and anemia (n = 2, 7.4 %) for FOLFIRI and G3-G4 thrombocytopenia (n = 2, 8.0 %), G4 nausea/vomiting (n = 1, 4.0 %) for CAPTEM. Three microRNAs emerged as NEC independent predictors. High expression values were found to be significantly associated with decreased PFS and OS.The safety profile of FOLFIRI and CAPTEM was manageable. FOLFIRI and CAPTEM chemotherapy showed comparable activity in the second-line setting after progression on etoposide/platinum.NCT03387592.Copyright © 2024. Published by Elsevier Ltd.