Chemotherapy objective response rates (ORRs) in metastatic soft tissue sarcoma (STS) are typically 20-40% with median progression-free survival (PFS) less than 6 months. Lurbinectedin is a new anticancer agent under investigation. The primary objective of this three-arm, phase II study was to determine the disease control rate (DCR = ORR + stable disease [SD]) at 24 weeks of lurbinectedin alone or with chemotherapy in STS. Eligible patients included adults with ≤2 prior cytotoxic therapies. Study cohorts were: stratum A (StrA; anthracycline-naive), lurbinectedin/doxorubicin; stratum B (StrB; prior anthracycline), lurbinectedin/gemcitabine; stratum C (StrC; prior anthracycline/gemcitabine) lurbinectedin monotherapy. Each stratum was analysed separately by Simon two-stage design. Forty-two patients were accrued (StrA = 20, StrB = 10, StrC = 12) including leiomyosarcoma [LMS] (n = 20), synovial sarcoma [SS](n = 4), malignant peripheral nerve sheath tumour (n = 3) and other STS histologies (n = 15). For StrA there were seven partial responses (PR) plus one stable disease (SD) at 24 weeks. For StrB, two patients met the 24-week DCR including one PR (leiomyosarcoma) and one SD (desmoplastic small round cell tumour [DSRCT]). StrB did not continue to the second stage. In StrC, no patients met the primary end-point. Median progression-free survival (PFS) was: StrA = 4.2 months (90% CI 1.4-7.8), StrB = 1.7 months (90% confidence interval (CI) 1.0-7.4), and StrC = 1.3 months (90% CI 1.1-3.0). Lurbinectedin as a single agent or with chemotherapy was well tolerated with haematologic adverse events (AE's) as the most common toxicity. There were no treatment-related deaths. The combination of lurbinectedin/doxorubicin reached the DCR end-point with seven PR and one patient with SD (ORR 35.0%, 24-week DCR 40.0%). Evidence of drug benefit was seen in leiomyosarcoma, dedifferentiated liposarcoma (DDLS), myxoid liposarcoma (MLS), synovial sarcoma (SS), and desmoplastic small round cell tumour (DSRCT). TRIAL REGISTRATION: clinicaltrials.gov; NCT02448537.

中文翻译：

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雷米替丁作为单一药物或与常规化疗联合用于转移性和/或不可切除肉瘤的II期多阶段研究。

转移性软组织肉瘤（STS）中的化疗客观反应率（ORR）通常为20％至40％，中位无进展生存期（PFS）少于6个月。Lurbinectin是一种正在研究的新型抗癌药。这项三臂II期研究的主要目标是确定单独使用lurbinectin或联合STS化疗24周时的疾病控制率（DCR = ORR +稳定疾病[SD]）。符合条件的患者包括接受≤2次细胞毒性治疗的成人。研究人群为：A层（StrA；未使用蒽环类药物），鲁比丁丁/阿霉素；B层（StrB；先前的蒽环类），鲁比丁丁/吉西他滨；C层（StrC；先前的蒽环类/吉西他滨）卢比替丁单药治疗。每个层均通过西蒙两阶段设计进行了单独分析。累积了42位患者（StrA = 20，StrB = 10，StrC = 12），包括平滑肌肉瘤[LMS]（n = 20），滑膜肉瘤[SS]（n = 4），恶性周围神经鞘瘤（n = 3）和其他STS组织学（n = 15）。对于StrA，在24周时有7个部分反应（PR）和1个稳定疾病（SD）。对于StrB，两名患者达到了24周的DCR，包括一名PR（平滑肌肉瘤）和一名SD（增生性小圆形细胞瘤[DSRCT]）。StrB没有继续到第二阶段。在StrC中，没有患者达到主要终点。中位无进展生存期（PFS）为：StrA = 4.2个月（90％CI 1.4-7.8），StrB = 1.7个月（90％置信区间（CI）1.0-7.4）和StrC = 1.3个月（90％CI 1.1） -3.0）。Lurbinectin作为单一药物或与化学疗法的耐受性最强，血液学不良事件（AE's）是最常见的毒性。没有与治疗有关的死亡。鲁比丁丁/阿霉素的组合达到DCR终点，有7名PR和1名SD患者（ORR 35.0％，24周DCR 40.0％）。在平滑肌肉瘤，去分化脂肪肉瘤（DDLS），粘液样脂肪肉瘤（MLS），滑膜肉瘤（SS）和增生性小圆形细胞瘤（DSRCT）中可以看到药物获益的证据。试验注册：clinicaltrials.gov；NCT02448537。