Medical Oncology, Hospital Ramón y Cajal, Madrid, Spain.
Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain.
Eur J Cancer. 2022 Sep;172:340-348. doi: 10.1016/j.ejca.2022.06.024. Epub 2022 Jul 10.
Patients with neuroendocrine tumours (NETs) need alternative therapies after failure of first-line therapy.
This phase II trial evaluated lurbinectedin, a selective inhibitor of oncogenic transcription, at 3.2 mg/m as a 1-h intravenous infusion every 3 weeks in 32 NETs patients treated in the second- or third-line setting. The primary efficacy endpoint was overall response rate (ORR) according to RECIST v1.1 assessed by the investigators. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety.
Two of 31 evaluable patients had confirmed partial responses (ORR = 6.5%; 95%CI, 0.8-21.4%). Median DoR was 4.7 months (95% CI, 4.0-5.4 months), median PFS was 1.4 months (95% CI, 1.2-3.0 months) and median OS was 7.4 months (95% CI, 3.4-16.2 months). Lurbinectedin showed an acceptable, predictable and manageable safety profile. The most common grade 3/4 toxicity was neutropenia (40.6%; grade 4, 12.4%; febrile neutropenia, 3.1%).
Considering the exploratory aim of this trial that evaluated a heterogeneous population of NETs patients, and the signs of antitumour activity observed (two confirmed partial responses and seven long disease stabilisations), further development of lurbinectedin is warranted in a more selected NETs population.
Sponsor Study Code: PM1183-B-005-14. EudraCT number: 2014-003773-42.
gov reference: NCT02454972.
神经内分泌肿瘤（NET）患者在一线治疗失败后需要替代疗法。
这项 II 期试验评估了 lurbinectedin，一种选择性致癌转录抑制剂，在二线或三线治疗的 32 名 NET 患者中，以 3.2mg/m 的剂量静脉输注 1 小时，每 3 周一次。主要疗效终点是研究者评估的根据 RECIST v1.1 标准的总缓解率（ORR）。次要终点包括缓解持续时间（DoR）、无进展生存期（PFS）、总生存期（OS）和安全性。
31 名可评估患者中有 2 名患者有确认的部分缓解（ORR=6.5%；95%CI，0.8-21.4%）。中位 DoR 为 4.7 个月（95%CI，4.0-5.4 个月），中位 PFS 为 1.4 个月（95%CI，1.2-3.0 个月），中位 OS 为 7.4 个月（95%CI，3.4-16.2 个月）。lurbinectedin 表现出可接受、可预测和可管理的安全性特征。最常见的 3/4 级毒性是中性粒细胞减少症（40.6%；4 级，12.4%；发热性中性粒细胞减少症，3.1%）。
考虑到这项试验的探索性目的，即评估了一组 NET 患者的异质性人群，以及观察到的抗肿瘤活性迹象（两名确认的部分缓解和七名疾病长期稳定），lurbinectedin 在更具选择性的 NET 患者人群中进一步开发是合理的。
赞助商研究代码：PM1183-B-005-14。EudraCT 编号：2014-003773-42。
gov 参考号：NCT02454972。
