这是一项多中心、单臂、II 期研究，旨在进一步探索曲贝替定作为腹膜后平滑肌肉瘤 (LMS) 和高分化/去分化脂肪肉瘤 (LPS) 的二线/二线治疗的活性。主要终点是生长调节指数 (GMI) 定义为曲贝替定 (PFS) 治疗期间的 PFS 与既往化疗期间的 PFS 之比：进展时间 (TTP-1)。次要终点是客观缓解率 (ORR) 和 PFS。根据方案，如果 GMI > 1.33，则患者被视为有反应；如果 <0.75，则被视为无反应；如果 0.76-1.32，则被视为无反应。总共 91 名患者可评估主要终点（32 名 LMS 患者和 59 名 LPS 患者）：接受的中位周期数为 6.0（Q1-Q3 3.0-12.0），72% 的患者停止治疗的主要原因是疾病进展。中位 PFS 为 6.0 个月，中位 TTP1 为 7.5 个月（LMS 和 LPS 分别为 8.1 个月和 6.4 个月）。 33 名患者 [52%，95% 置信区间 (CI) 36% 至 58%，P = 0.674，响应几率 1.1] 的 GMI >1.33（LMS 46%，95% CI 26% 至 67%，几率响应 0.85；LPS 56%，95% CI 40% 至 72%，响应几率 1.3）。总体而言，在 LPS 中，我们观察到 15/47 名患者的 GMI <0.5 和 15/47 名患者的 GMI >2。在 LMS 患者中，9/26 的 GMI <0.5，10/26 的 GMI >2。总体而言，ORR（完全缓解、部分缓解）为 16%（LMS 为 24%，LPS 为 12%）。虽然未达到研究的主要终点，但我们注意到与曲贝替定相比，有一组患者的 TTP 存在显着差异与之前的治疗相比（GMI <0.5 或 >2，后者包括一些使用曲贝替定治疗后 TTP 较长的患者）。观察到 PFS 和总生存期之间存在不匹配，这可能是由于两种不同组织学的自然史以及 LMS 中可用的更多细胞系所致。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

This is a multicentre, single-arm, phase II study aimed at further exploring the activity of trabectedin as second-/further-line treatment in retroperitoneal leiomyosarcoma (LMS) and well-differentiated/dedifferentiated liposarcoma (LPS).The primary endpoint was the growth modulation index (GMI) defined as the ratio between PFS under trabectedin (PFS) and during previous chemotherapy treatment: time to progression (TTP-1). Secondary endpoints were objective response rate (ORR) and PFS. As per protocol, patients were considered responders if the GMI was >1.33, non-responders if <0.75 and neither if 0.76-1.32.Overall 91 patients were assessable for the primary endpoint (32 patients with LMS and 59 patients with LPS): the median number of cycles received was 6.0 (Q1-Q3 3.0-12.0), and the main reason for treatment discontinuation was disease progression in 72% of patients. The median PFS was 6.0 months, while the median TTP1 was 7.5 months (8.1 and 6.4 months for LMS and LPS, respectively). Thirty-three patients [52%, 95% confidence interval (CI) 36% to 58%, P = 0.674, odds of response 1.1] had a GMI >1.33 (LMS 46%, 95% CI 26% to 67%, odds of response 0.85; LPS 56%, 95% CI 40% to 72%, odds of response 1.3). Overall, in LPS we observed 15/47 patients with a GMI <0.5 and 15/47 patients with a GMI >2. Among LMS patients, 9/26 had a GMI <0.5 and 10/26 had a GMI >2. Overall, ORR (complete response + partial response) was 16% (24% for LMS and 12% for LPS).While the primary endpoint of the study was not met, we noticed a subgroup of patients with a markedly discrepant TTP with trabectedin in comparison to previous therapy (GMI <0.5 or >2, the latter including some patients with a long TTP with trabectedin). A mismatch between PFS and overall survival was observed, possibly due to the natural history of the two different histologies and the availability of further lines in LMS.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.