Osteoncology and Rare Tumor Center (CDO-TR), IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
Bioscience Laboratory, Preclinic and Osteoncology Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
Eur J Cancer. 2024 Sep;208:114129. doi: 10.1016/j.ejca.2024.114129. Epub 2024 May 25.
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.
神经内分泌癌（NEC）的预后较差。铂类一线治疗失败后，目前尚无公认的标准二线治疗方法。FOLFIRI 和 CAPTEM 方案在初步研究中显示出有前景的活性。我们旨在评估这些方案在转移性 NEC 患者中的疗效。
这是一项开放标签、多中心、随机非对照的 II 期临床试验，旨在评估 FOLFIRI 或 CAPTEM 在转移性 NEC 患者中的疗效和安全性。主要终点是根据 RECIST v1.1 由研究者评估的 12 周疾病控制率（12w-DCR）和 CTCAE v5.0 评估的安全性。其他终点包括总缓解率（ORR）、无进展生存期（PFS）和总生存期（OS）。对患者的血清样本进行 NGS miRNome 分析，与健康供体进行比较，以揭示作为候选循环生物标志物的差异表达 miRNA。
中期分析显示，由于未达到需要 25 名患者中的 10 名达到 12 周 DCR 的最低阈值，该研究因无效而停止。从 2017 年 6 月 3 日至 2021 年 1 月 18 日，共有 112 名患者中的 53 名入组。中位随访时间为 22.6 个月（范围：1.4-60.4）。FOLFIRI 组的 12 周 DCR 为 39.1%，而 CAPTEM 组为 28.0%。FOLFIRI 亚组的 12 个月 OS 率为 28.4%（95%CI：12.7-46.5），而 CAPTEM 亚组为 32.4%（95%CI：14.9-51.3）。最常见的 G3-G4 级副作用是中性粒细胞减少（n=5，18.5%）和贫血（n=2，7.4%）（FOLFIRI）和血小板减少症（n=2，8.0%）、G4 级恶心/呕吐（n=1，4.0%）（CAPTEM）。三种 microRNAs 被确定为 NEC 的独立预测因子。高表达值与 PFS 和 OS 降低显著相关。
FOLFIRI 和 CAPTEM 的安全性是可控的。FOLFIRI 和 CAPTEM 化疗在依托泊苷/铂类进展后的二线治疗中显示出相当的活性。
NCT03387592。
