Fondazione IRCC Istituto Nazionale Tumori, Medical Oncology 2, Milan.
Oncology Unit, IRCCS Istituto Candiolo, Turin.
ESMO Open. 2024 Aug;9(8):103667. doi: 10.1016/j.esmoop.2024.103667. Epub 2024 Aug 8.
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.
这是一项多中心、单臂、二期研究，旨在进一步探索曲贝替定在腹膜后平滑肌肉瘤（LMS）和高分化/去分化脂肪肉瘤（LPS）二线/后线治疗中的活性。
主要终点是生长调节指数（GMI），定义为曲贝替定（PFS）期间和之前化疗期间无进展生存期（TTP-1）的比值。次要终点是客观缓解率（ORR）和无进展生存期。根据方案，如果 GMI >1.33，则患者被认为是有反应者，如果 GMI <0.75，则患者被认为是无反应者，如果 GMI 在 0.76-1.32 之间，则患者被认为是无反应者。
共有 91 名患者可评估主要终点（32 名 LMS 患者和 59 名 LPS 患者）：接受的中位数周期数为 6.0（Q1-Q3 为 3.0-12.0），72%的患者因疾病进展而停止治疗。中位无进展生存期为 6.0 个月，中位 TTP1 为 7.5 个月（LMS 和 LPS 分别为 8.1 和 6.4 个月）。33 名患者[52%，95%置信区间（CI）36%至 58%，P=0.674，反应可能性 1.1]的 GMI >1.33（LMS 为 46%，95%CI 26%至 67%，反应可能性 0.85；LPS 为 56%，95%CI 40%至 72%，反应可能性 1.3）。总体而言，在 LPS 中，我们观察到 15/47 名患者的 GMI <0.5，15/47 名患者的 GMI >2。在 LMS 患者中，9/26 名患者的 GMI <0.5，10/26 名患者的 GMI >2。总体而言，ORR（完全缓解+部分缓解）为 16%（LMS 为 24%，LPS 为 12%）。
虽然该研究的主要终点未达到，但我们注意到一个亚组患者的 TTP 与曲贝替定相比明显不同（GMI <0.5 或 >2，后者包括一些曲贝替定治疗 TTP 较长的患者）。无进展生存期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和 LMS 中进一步治疗的可用性所致。
