Efficacy, safety, and pharmacokinetics of eribulin as monotherapy or in combination with irinotecan for patients with pediatric rhabdomyosarcoma, non-rhabdomyosarcoma soft tissue sarcoma, or Ewing sarcoma

IF 8.3 2区医学 Q1 ONCOLOGY ESMO Open Pub Date : 2025-02-01 Epub Date: 2025-02-04 DOI:10.1016/j.esmoop.2024.104129

M. Casanova , C.M. Albert , F. Bautista , S.C. Borinstein , S. Bradfield , A. Bukowinski , Q. Campbell-Hewson , D.S. Hawkins , A. Kim , G.M. Milano , L.V. Marshall , N. Pinto , C.A. Pratilas , A. Rubio-San-Simón , R. Windsor , O. Majid , R. Scott , Y. Jia , C. Paoletti , U. Kontny

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Abstract

Background

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).

Patients and methods

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/m² on days 1 and 8 (Study 223) or eribulin 1.4 mg/m² on days 1 and 8 plus irinotecan 40 mg/m² 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.

Results

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).

Conclusions

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.

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伊立替康单药或联合伊立替康治疗小儿横纹肌肉瘤、非横纹肌肉瘤软组织肉瘤或尤文氏肉瘤的疗效、安全性和药代动力学

在本报告中，我们介绍了伊立替康单药治疗（研究223）和联合伊立替康治疗复发/难治性小儿横纹肌肉瘤（RMS）、非横纹肌肉瘤软组织肉瘤（NRSTS）或尤文氏肉瘤（EWS）的研究结果。患者和方法研究223和213是II期多中心试验，纳入了组织学证实的儿童患者。治疗包括在第1天和第8天使用甲酸埃瑞布林1.4 mg/m2（研究223）或在第1天和第8天使用埃瑞布林1.4 mg/m2加伊立替康40 mg/m2在第1天和第5天使用（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。结果研究223中，21例患者(RMS, n = 8；NRSTS, n = 8；EWS, n = 5)入组治疗。未观察到应答，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, n = 3；NRSTS, n = 1；EWS （n = 2）病情稳定≥5周。所有患者均有一个或多个治疗不良事件（TEAE），最常见的是中性粒细胞计数下降（71.4%）。在Study 213 （II期部分）中，27例患者(RMS, n = 9；NRSTS, n = 9；EWS, n = 9)入组/治疗。截至数据截止日期（2021年7月9日），3例患者（每组1例）出现缓解，ORR为11.1%，DORs为2.9个月（RMS）、1.4个月（NRSTS）和15.4个月（EWS）。所有患者均有一次或多次TEAE，最常见的是腹泻和中性粒细胞计数下降（各51.9%）。结论：无论是单药治疗还是联合治疗，seribulin在成人人群中的安全性与之前观察到的一致；然而，这两项研究的疗效被认为不足以推进这些疾病领域的研究。

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来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.