Casanova M, Albert C M, Bautista F, Borinstein S C, Bradfield S, Bukowinski A, Campbell-Hewson Q, Hawkins D S, Kim A, Milano G M, Marshall L V, Pinto N, Pratilas C A, Rubio-San-Simón A, Windsor R, Majid O, Scott R, Jia Y, Paoletti C, Kontny U
Pediatric Oncology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Division of Hematology, Oncology, Bone Marrow Transplant and Cellular Therapy, Seattle Children's Hospital, Seattle; Department of Pediatrics, University of Washington School of Medicine, Seattle, USA.
ESMO Open. 2025 Feb;10(2):104129. doi: 10.1016/j.esmoop.2024.104129. Epub 2025 Feb 4.
In this report, we present results from studies of eribulin as monotherapy (Study 223) and in combination with irinotecan (the phase II part of Study 213) for patients with relapsed/refractory pediatric rhabdomyosarcoma (RMS), non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), or Ewing sarcoma (EWS).
Studies 223 and 213 were phase II multicenter trials that enrolled pediatric patients with histologically confirmed disease. Treatment comprised 21-day cycles of eribulin mesylate 1.4 mg/m on days 1 and 8 (Study 223) or eribulin 1.4 mg/m on days 1 and 8 plus irinotecan 40 mg/m on days 1-5 (Study 213). For both studies, the primary endpoints were objective response rate (ORR) and duration of response (DOR); secondary endpoint included safety.
In Study 223, 21 patients (RMS, n = 8; NRSTS, n = 8; EWS, n = 5) were enrolled and treated. No responses were observed, resulting in early termination of enrollment. By the data cut-off date (22 February 2021), six patients (RMS, n = 3; NRSTS, n = 1; EWS, n = 2) had stable disease for ≥5 weeks. All patients had one or more treatment-emergent adverse event (TEAE), most commonly neutrophil count decreased (71.4%). In Study 213 (phase II part), 27 patients (RMS, n = 9; NRSTS, n = 9; EWS, n = 9) were enrolled/treated. By the data cut-off date (9 July 2021), three patients (one in each cohort) had had a response, resulting in an ORR of 11.1% and DORs of 2.9 (RMS), 1.4 (NRSTS), and 15.4 (EWS) months. All patients had one or more TEAE, most commonly diarrhea and neutrophil count decreased (51.9% each).
Eribulin, as monotherapy or combination therapy, exhibited a safety profile consistent with that observed previously in adult populations; however, efficacy in both studies was not considered adequate to advance investigation in these disease areas.
在本报告中，我们展示了对艾日布林作为单一疗法（研究223）以及与伊立替康联合使用（研究213的II期部分）用于复发/难治性小儿横纹肌肉瘤（RMS）、非横纹肌肉瘤软组织肉瘤（NRSTS）或尤因肉瘤（EWS）患者的研究结果。
研究223和213为II期多中心试验，纳入组织学确诊疾病的儿科患者。治疗方案为第1天和第8天静脉滴注甲磺酸艾日布林1.4mg/m²（研究223），或第1天和第8天静脉滴注艾日布林1.4mg/m²，同时第1 - 5天静脉滴注伊立替康40mg/m²（研究213）。两项研究的主要终点均为客观缓解率（ORR）和缓解持续时间（DOR）；次要终点包括安全性。
在研究223中，共纳入并治疗了21例患者（RMS 8例、NRSTS 8例、EWS 5例）。未观察到缓解，导致提前终止入组。截至数据截止日期（2021年2月22日），6例患者（RMS 3例、NRSTS 1例、EWS 2例）疾病稳定≥5周。所有患者均发生了1种或更多种治疗中出现的不良事件（TEAE），最常见的是中性粒细胞计数减少（71.4%）。在研究213（II期部分）中，共纳入并治疗了27例患者（RMS 9例、NRSTS 9例、EWS 9例）。截至数据截止日期（2021年7月9日），3例患者（每个队列各1例）出现缓解，ORR为11.1%，DOR分别为2.9个月（RMS）、1.4个月（NRSTS）和15.4个月（EWS）。所有患者均发生了1种或更多种TEAE，最常见的是腹泻和中性粒细胞计数减少（各51.9%）。
艾日布林作为单一疗法或联合疗法，其安全性与先前在成人患者中观察到的一致；然而，两项研究中的疗效均未达到足以推进这些疾病领域进一步研究的水平。
