Clinic for Internal Medicine IV-Hematology/Oncology, University Clinic, Martin Luther University, Halle-Wittenberg, Germany.
Department of Medicine III, University Hospital, Ludwig Maximilians University, Munich, Germany.
JAMA Oncol. 2021 Feb 1;7(2):255-262. doi: 10.1001/jamaoncol.2020.6564.
Pazopanib and gemcitabine have shown good tolerability, albeit modest single-agent activity in pretreated soft tissue sarcoma. A combined regimen to improve outcomes is required.
To determine the efficacy of gemcitabine and pazopanib compared with pazopanib alone.
DESIGN, SETTING, AND PARTICIPANTS: This multicenter, randomized phase 2 clinical trial was conducted in Germany from September 2011 to July 2014 and included patients with an Eastern Cooperative Oncology Group performance status score of 0 to 2, adequate organ function, measurable lesion, and progression after at least 1 prior treatment with anthracyclines and/or ifosfamide. Data analysis was performed during 2019 and 2020.
Patients were randomized to pazopanib with gemcitabine (A) or without gemcitabine (B).
The primary end point was progression-free survival rate (PFSR) at 12 weeks; secondary end points included toxicity, quality of life, overall survival, and response rates.
A total of 90 patients were randomized, and 86 eligible patients (43 women [50%]) were evaluable, with a median age of 57 (range, 22-84) years and Eastern Cooperative Oncology Group performance status score of 0/1 in 77 participants (90%). The predominant histological subtypes were leiomyosarcoma (22 [26%]) and liposarcoma (16 [19%]). After a median follow-up of 12.4 (range, 1-48) months, the primary end point was met, with a PFSR at 12 weeks of 74% (A) vs 47% (B) (hazard ratio [HR], 1.60; 90% CI, 1.15-2.23; P = .01). In the combination arm, PFSR was significantly longer, with a median of 5.6 vs 2.0 months (HR, 0.58; 95% CI, 0.36-0.92; P = .02) compared with single-agent pazopanib, whereas overall survival was similar, with 13.1 vs 11.2 months (HR, 0.98; 95% CI, 0.60-1.58; P = .83). The objective response rate was overall low, with 11% (A) vs 5% (B) (P = .10). The toxicity of the combination of pazopanib and gemcitabine was increased, but it was manageable and mainly hematological.
This phase 2 randomized clinical trial of patients with soft tissue sarcoma found that the addition of gemcitabine to pazopanib was tolerable, and PFSR at 12 weeks was significantly higher compared with pazopanib alone. These results suggest clinical activity of the combination, but they should be confirmed in a phase 3 trial in a more homogeneous population (eg, leiomyosarcoma).
German Clinical Trials Identifier: DRKS00003139.
重要性：帕唑帕尼联合吉西他滨治疗软组织肉瘤显示出良好的耐受性，尽管单一药物活性较低。需要联合治疗方案以改善预后。
目的：确定与单独使用帕唑帕尼相比，吉西他滨联合帕唑帕尼的疗效。
设计、地点和参与者：这是一项多中心、随机的 2 期临床试验，于 2011 年 9 月至 2014 年 7 月在德国进行，纳入了东部合作肿瘤学组表现状态评分为 0-2、器官功能良好、可测量病变且在至少 1 次蒽环类药物和/或异环磷酰胺治疗后进展的患者。数据分析于 2019 年和 2020 年进行。
干预措施：患者随机分为帕唑帕尼联合吉西他滨（A 组）或不联合吉西他滨（B 组）。
主要终点：12 周时无进展生存率（PFSR）；次要终点包括毒性、生活质量、总生存率和缓解率。
结果：共随机分配了 90 名患者，86 名符合条件的患者（43 名女性[50%]）可进行评估，中位年龄为 57 岁（范围为 22-84 岁），东部合作肿瘤学组表现状态评分为 0/1 的有 77 名参与者（90%）。主要组织学亚型为平滑肌肉瘤（22 例[26%]）和脂肪肉瘤（16 例[19%]）。中位随访 12.4 个月（范围为 1-48 个月）后，主要终点达到，12 周时 A 组的 PFSR 为 74%，B 组为 47%（HR，1.60；90%CI，1.15-2.23；P=0.01）。联合组 PFSR 明显更长，中位时间为 5.6 个月 vs 2.0 个月（HR，0.58；95%CI，0.36-0.92；P=0.02），而总生存率相似，中位时间为 13.1 个月 vs 11.2 个月（HR，0.98；95%CI，0.60-1.58；P=0.83）。客观缓解率总体较低，A 组为 11%，B 组为 5%（P=0.10）。帕唑帕尼联合吉西他滨的毒性增加，但可管理且主要为血液学毒性。
结论和相关性：这项针对软组织肉瘤患者的 2 期随机临床试验发现，与单独使用帕唑帕尼相比，吉西他滨联合帕唑帕尼耐受性良好，12 周时的 PFSR 显著提高。这些结果表明联合治疗具有临床活性，但需要在更同质的人群（如平滑肌肉瘤）中进行 3 期试验来证实。
试验注册：德国临床试验注册中心标识符：DRKS00003139。
