背景:这是一个多中心,单臂,II期研究旨在进一步探索trabectedin在腹膜后平滑肌肉瘤(LMS)和高分化/去分化脂肪肉瘤(LPS)中作为二线/进一步线治疗的活性。
方法:主要终点是生长调节指数(GMI),定义为trabectedin下的PFS(PFS)与先前化疗期间的PFS之间的比率:进展时间(TTP-1)。次要终点是客观缓解率(ORR)和PFS。根据协议,如果GMI>1.33,则患者被认为是应答者,如果<0.75,则为无应答者,如果为0.76-1.32,则均为无应答者.
结果:共有91例患者可评估主要终点(32例LMS患者和59例LPS患者):接受的周期中位数为6.0(Q1-Q33.0-12.0),治疗中断的主要原因是72%的患者出现疾病进展。中位PFS为6.0个月,而中位TTP1为7.5个月(LMS和LPS的8.1和6.4个月,分别)。33名患者[52%,95%置信区间(CI)36%至58%,P=0.674,反应几率1.1]的GMI>1.33(LMS46%,95%CI26%至67%,应答几率0.85;LPS56%,95%CI40%至72%,响应几率1.3)。总的来说,在LPS中,我们观察到15/47患者的GMI<0.5和15/47患者的GMI>2。在LMS患者中,9/26的GMI<0.5,10/26的GMI>2。总的来说,ORR(完全反应+部分反应)为16%(LMS为24%,LPS为12%)。
结论:虽然未达到研究的主要终点,我们注意到,与以前的治疗相比,TTP与trabectedin显著差异的患者亚组(GMI<0.5或>2,后者包括一些TTP与trabectedin的患者).观察到PFS和总生存期不匹配,可能是由于两种不同组织学的自然史以及LMS中其他细胞系的可用性。
BACKGROUND: 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).
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.