BACKGROUND Options in second-line therapy after doxorubicin-based chemotherapy for metastatic/advanced leiomyosarcoma include gemcitabine (G), trabectedin and pazopanib (P) monotherapy. Currently, no combination therapy is better than monotherapy. LMS03 is an open-label multicentre single-group phase II study designed to assess the efficacy and tolerance of G + P in the second-line setting. PATIENTS AND METHODS Patients (pts), ECOG ≤2, with metastatic leiomyosarcomas (LMS) after first-line doxorubicin chemotherapy failure were eligible. Pts were treated with G 1000 mg/m2 on days 1 and 8 of each 21 days (maximum eight cycles), in combination with oral daily P (800 mg), until disease progression/toxicity. 9-month progression-free survival (PFS) rate was the primary endpoint. Inacceptable and promising 9-month PFS rates were defined, in the intent-to-treat population, as 32% and 44%. RESULTS 106 pts were included with a mean age of 59.8 years and an ECOG 0 in 63.5%; the primary tumour site was uterus in 61%. Pts were treated with P + G for a median of 3.8 mo, and P for a median of 4.2 mo. The 9-month PFS rate was 32.1% (95% CI 23.1-41.1). After a median follow-up of 14.2 months, the PFS was 6.5 months (95% CI 5.6-8.2), and the overall survival was 22.4 months (95% CI 16.9-26.5). The best response was 23.8%. The most frequent reported grade 3-4 adverse events were haematological. CONCLUSIONS LMS03 failed to show that second-line therapy, with gemcitabine combined with pazopanib, followed by pazopanib alone, was beneficial for advanced LMS patients. Eudract N°2011-001308-36 and NCT01442662.

中文翻译：

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吉西他滨二期联合帕唑帕尼联合帕唑帕尼维持治疗，作为晚期平滑肌肉瘤患者的二线治疗：法国肉瘤小组研究（LMS03研究）。

背景技术在基于阿霉素的化疗后用于转移性/高级平滑肌肉肉瘤的二线治疗中，吉西他滨（G），曲贝汀和帕唑帕尼（P）单药治疗的选择。目前，没有任何一种联合疗法比单一疗法更好。LMS03是一项开放标签的多中心单组II期研究，旨在评估二线治疗中G + P的疗效和耐受性。患者和方法一线阿霉素化疗失败后转移性平滑肌肉瘤（LMS）的ECOG≤2的患者（pts）是合格的。在每21天的第1天和第8天（最多八个周期）以G 1000 mg / m2 G联合口服每日P（800 mg）治疗Pts，直至疾病进展/毒性。主要终点为9个月无进展生存（PFS）率。定义了无法接受且很有希望的9个月PFS率，在意向性治疗人群中，这一比例分别为32％和44％。结果纳入106分，平均年龄59.8岁，ECOG 0为63.5％。原发肿瘤部位占子宫的占61％。用P + G处理Pts的中位数为3.8 mo，使用P进行中值的4.2 mo。9个月的PFS率为32.1％（95％CI 23.1-41.1）。中位随访14.2个月后，PFS为6.5个月（95％CI 5.6-8.2），总生存期为22.4个月（95％CI 16.9-26.5）。最好的答复是23.8％。报告的最常见的3-4级不良事件是血液学。结论LMS03未能显示吉西他滨联合帕唑帕尼联合单独使用帕唑帕尼的二线治疗对晚期LMS患者有益。Eudract N°2011-001308-36和NCT01442662。8年，ECOG 0占63.5％；原发肿瘤部位占子宫的占61％。用P + G处理Pts的中位数为3.8 mo，使用P进行中值的4.2 mo。9个月的PFS率为32.1％（95％CI 23.1-41.1）。中位随访14.2个月后，PFS为6.5个月（95％CI 5.6-8.2），总生存期为22.4个月（95％CI 16.9-26.5）。最好的答复是23.8％。报告的最常见的3-4级不良事件是血液学。结论LMS03未能显示吉西他滨联合帕唑帕尼联合单独使用帕唑帕尼的二线治疗对晚期LMS患者有益。Eudract N°2011-001308-36和NCT01442662。8年，ECOG 0占63.5％；61％的原发肿瘤部位是子宫。用P + G处理Pts的中位数为3.8 mo，使用P进行中值的4.2 mo。9个月的PFS率为32.1％（95％CI 23.1-41.1）。中位随访14.2个月后，PFS为6.5个月（95％CI 5.6-8.2），总生存期为22.4个月（95％CI 16.9-26.5）。最好的答复是23.8％。报告的最常见的3-4级不良事件是血液学。结论LMS03未能显示吉西他滨联合帕唑帕尼联合单独使用帕唑帕尼的二线治疗对晚期LMS患者有益。Eudract N°2011-001308-36和NCT01442662。1％（95％CI 23.1-41.1）。中位随访14.2个月后，PFS为6.5个月（95％CI 5.6-8.2），总生存期为22.4个月（95％CI 16.9-26.5）。最好的答复是23.8％。报告的最常见的3-4级不良事件是血液学。结论LMS03未能显示吉西他滨联合帕唑帕尼联合单独使用帕唑帕尼的二线治疗对晚期LMS患者有益。Eudract N°2011-001308-36和NCT01442662。1％（95％CI 23.1-41.1）。中位随访14.2个月后，PFS为6.5个月（95％CI 5.6-8.2），总生存期为22.4个月（95％CI 16.9-26.5）。最好的答复是23.8％。报告的最常见的3-4级不良事件是血液学。结论LMS03未能显示吉西他滨联合帕唑帕尼联合单独使用帕唑帕尼的二线治疗对晚期LMS患者有益。Eudract N°2011-001308-36和NCT01442662。其次是帕唑帕尼，对晚期LMS患者有益。Eudract N°2011-001308-36和NCT01442662。其次是帕唑帕尼，对晚期LMS患者有益。Eudract N°2011-001308-36和NCT01442662。