Medical Oncology Department, University Hospital Virgen del Rocio, Seville, Spain; Institute of Biomedicine of Seville (University Hospital Virgen del Rocio; Spanish National Research Council; University of Seville), Seville, Spain.
Medical Oncology Department, University Hospital of Canarias, Tenerife, Spain.
Lancet Oncol. 2020 Mar;21(3):456-466. doi: 10.1016/S1470-2045(19)30826-5. Epub 2020 Feb 14.
Solitary fibrous tumour is an ultra-rare sarcoma, which encompasses different clinicopathological subgroups. The dedifferentiated subgroup shows an aggressive course with resistance to pazopanib, whereas in the malignant subgroup, pazopanib shows higher activity than in previous studies with chemotherapy. We designed a trial to test pazopanib activity in two different cohorts of solitary fibrous tumour: the malignant-dedifferentiated cohort, which was previously published, and the typical cohort, which is presented here.
In this single-arm, phase 2 trial, adult patients (aged ≥18 years) diagnosed with confirmed metastatic or unresectable typical solitary fibrous tumour of any location, who had progressed in the previous 6 months (by Choi criteria or Response Evaluation Criteria in Solid Tumors [RECIST]) and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 were enrolled at 11 tertiary hospitals in Italy, France, and Spain. Patients received pazopanib 800 mg once daily, taken orally, until progression, unacceptable toxicity, withdrawal of consent, non-compliance, or a delay in pazopanib administration of longer than 3 weeks. The primary endpoint was proportion of patients achieving an overall response measured by Choi criteria in patients who received at least 1 month of treatment with at least one radiological assessment. All patients who received at least one dose of the study drug were included in the safety analyses. This study is registered in ClinicalTrials.gov, NCT02066285, and with the European Clinical Trials Database, EudraCT 2013-005456-15.
From June 26, 2014, to Dec 13, 2018, of 40 patients who were assessed, 34 patients were enrolled and 31 patients were included in the response analysis. Median follow-up was 18 months (IQR 14-34), and 18 (58%) of 31 patients had a partial response, 12 (39%) had stable disease, and one (3%) showed progressive disease according to Choi criteria and central review. The proportion of overall response based on Choi criteria was 58% (95% CI 34-69). There were no deaths caused by toxicity, and the most frequent adverse events were diarrhoea (18 [53%] of 34 patients), fatigue (17 [50%]), and hypertension (17 [50%]).
To our knowledge, this is the first prospective trial of pazopanib for advanced typical solitary fibrous tumour. The manageable toxicity and activity shown by pazopanib in this cohort suggest that this drug could be considered as first-line treatment for advanced typical solitary fibrous tumour.
Spanish Group for Research on Sarcomas (GEIS), Italian Sarcoma Group (ISG), French Sarcoma Group (FSG), GlaxoSmithKline, and Novartis.
孤立性纤维瘤是一种极为罕见的肉瘤，包含不同的临床病理亚组。去分化亚组表现出侵袭性病程，对帕唑帕尼耐药，而在恶性亚组中，帕唑帕尼的活性高于既往化疗研究。我们设计了一项试验，以测试帕唑帕尼在孤立性纤维瘤的两个不同队列中的活性：去分化/恶性队列，之前已发表，本研究报告典型队列。
在这项单臂、2 期试验中，在意大利、法国和西班牙的 11 家三级医院招募了年龄≥18 岁、经组织学证实的转移性或不可切除的任何部位典型孤立性纤维瘤的成年患者（既往符合 Choi 标准或实体瘤反应评价标准 [RECIST] 进展）和东部肿瘤协作组（ECOG）体能状态为 0-2。患者接受帕唑帕尼 800 mg 每日一次，口服，直至疾病进展、不可耐受毒性、患者撤回同意、不依从、或帕唑帕尼给药延迟超过 3 周。主要终点是根据 Choi 标准评估的至少接受 1 个月至少 1 次影像学评估的患者中总体缓解的患者比例。所有至少接受 1 次研究药物治疗的患者均纳入安全性分析。本研究在 ClinicalTrials.gov 注册，NCT02066285，并在欧洲临床试验数据库 EudraCT 2013-005456-15 注册。
自 2014 年 6 月 26 日至 2018 年 12 月 13 日，共评估了 40 例患者，34 例患者入组，31 例患者纳入缓解分析。中位随访时间为 18 个月（IQR 14-34），根据 Choi 标准和中心评估，18 例（58%）患者有部分缓解，12 例（39%）患者疾病稳定，1 例（3%）患者疾病进展。基于 Choi 标准的总缓解率为 58%（95%CI 34-69）。无因毒性导致的死亡，最常见的不良反应是腹泻（34 例患者中有 18 例[53%]）、乏力（17 例[50%]）和高血压（17 例[50%]）。
据我们所知，这是首个前瞻性帕唑帕尼治疗晚期典型孤立性纤维瘤的试验。在该队列中，帕唑帕尼显示出可管理的毒性和活性，这表明该药可考虑作为晚期典型孤立性纤维瘤的一线治疗药物。
西班牙肉瘤研究小组（GEIS）、意大利肉瘤研究小组（ISG）、法国肉瘤研究小组（FSG）、葛兰素史克和诺华。
