Sarcoma Unit, Royal Marsden Hospital and Institute of Cancer Research, London, United Kingdom.
The University of Texas MD Anderson Cancer Center, Houston, Texas.
JAMA Oncol. 2022 May 1;8(5):740-747. doi: 10.1001/jamaoncol.2021.3547.
Angiosarcoma is a rare sarcoma subtype with a poor outcome. Carotuximab plus pazopanib produced a median progression-free survival (PFS) of 7.8 months in pazopanib-naive patients with chemotherapy-refractory angiosarcoma in a phase 1/2 trial.
To determine whether carotuximab plus pazopanib improves PFS compared with pazopanib alone in patients with advanced angiosarcoma.
DESIGN, SETTING, AND PARTICIPANTS: The TAPPAS Trial: An Adaptive Enrichment Phase 3 Trial of TRC105 and Pazopanib vs Pazopanib Alone in Patients With Advanced Angiosarcoma was a multinational, multicenter, open-label, parallel-group, phase 3 randomized clinical trial of 123 patients 18 years or older with advanced angiosarcoma that was conducted between February 16, 2017, and April 12, 2019, at 31 sites in the US and the European Union. Patients were randomized 1:1 to receive pazopanib alone or carotuximab plus pazopanib. The trial incorporated an adaptive enrichment design. Inclusion criteria were no more than 2 prior lines of systemic therapy and an Eastern Cooperative Oncology Group performance status of 0 or 1. The efficacy analysis used the intent-to-treat population; the safety analysis included all patients who received a dose of either study drug.
Oral pazopanib, 800 mg/d, or intravenous carotuximab, 10 mg/kg, administered weekly, plus oral pazopanib, 800 mg/d, with dose modification allowed per patient tolerance or until disease progression.
The primary end point was PFS, assessed by blinded independent radiographic and cutaneous photographic review per Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, version 1.1. Secondary end points included the objective response rate and overall survival. An interim analysis to determine the final sample size was conducted after enrollment of 123 patients. PFS in the group receiving pazopanib alone was compared with PFS in the group receiving carotuximab plus pazopanib using the log rank test.
Of 114 patients with evaluable data (53 in the pazopanib arm and 61 in the carotuximab plus pazopanib arm), 69 (61%) were female and the median age was 68 years (range, 24-82 years); 57 (50%) had cutaneous disease and 32 (28%) had had no prior treatment. The primary end point (PFS) was not reached (hazard ratio [HR], 0.98; 95% CI, 0.52-1.84; P = .95), with a median of 4.3 months (95% CI, 2.9 months to not reached) for pazopanib and 4.2 months (95% CI, 2.8-8.3 months) for the combination arm. The most common all-grade adverse events in the single-agent pazopanib arm vs the combination arm were fatigue (29 patients [55%] vs 37 [61%]), headache (12 patients [23%] vs 39 [64%]), diarrhea (27 patients [51%] vs 35 [57%]), nausea (26 patients [49%] vs 29 [48%]), vomiting (12 patients [23%] vs 23 [38%]), anemia (5 patients [9%] vs 27 [44%]), epistaxis (2 patients [4%] vs 34 [56%]), and hypertension (29 patients [55%] vs 22 [36%]).
In this phase 3 randomized clinical trial, carotuximab plus pazopanib did not improve PFS compared with pazopanib alone in patients with advanced angiosarcoma.
ClinicalTrials.gov Identifier: NCT02979899.
血管肉瘤是一种罕见的肉瘤亚型，预后不良。在一项 1/2 期试验中，卡妥昔单抗联合帕唑帕尼在化疗耐药性血管肉瘤的帕唑帕尼初治患者中，中位无进展生存期（PFS）为 7.8 个月。
确定卡妥昔单抗联合帕唑帕尼与单独使用帕唑帕尼相比，在晚期血管肉瘤患者中的 PFS 是否有所改善。
设计、地点和参与者：TAPPAS 试验：TRC105 和帕唑帕尼与帕唑帕尼单独治疗晚期血管肉瘤患者的适应性富集 3 期试验是一项多中心、开放标签、平行组、3 期随机临床试验，纳入了 31 个美国和欧盟的研究地点，共纳入了 123 名年龄在 18 岁及以上的晚期血管肉瘤患者，这些患者在 2017 年 2 月 16 日至 2019 年 4 月 12 日之间接受了治疗。患者按 1:1 的比例随机接受帕唑帕尼单药治疗或卡妥昔单抗联合帕唑帕尼治疗。该试验采用了适应性富集设计。纳入标准为不超过 2 线系统治疗和东部合作肿瘤组（ECOG）表现状态 0 或 1。疗效分析采用意向治疗人群；安全性分析包括所有接受研究药物剂量的患者。
口服帕唑帕尼，800mg/d，或静脉注射卡妥昔单抗，10mg/kg，每周给药，加用口服帕唑帕尼，800mg/d，允许根据患者耐受或疾病进展情况调整剂量。
主要终点是无进展生存期（PFS），通过盲法独立影像学和皮肤摄影评估根据实体瘤反应评估标准（RECIST），版本 1.1 进行评估。次要终点包括客观缓解率和总生存期。在纳入 123 例患者后，进行了中期分析以确定最终样本量。单独使用帕唑帕尼组的 PFS 与使用卡妥昔单抗联合帕唑帕尼组的 PFS 进行比较，采用对数秩检验。
在 114 例可评估数据的患者中（帕唑帕尼组 53 例，卡妥昔单抗联合帕唑帕尼组 61 例），69 例（61%）为女性，中位年龄为 68 岁（范围，24-82 岁）；57 例（50%）为皮肤疾病，32 例（28%）无既往治疗。主要终点（PFS）未达到（危险比[HR]，0.98；95%CI，0.52-1.84；P=0.95），帕唑帕尼组的中位 PFS 为 4.3 个月（95%CI，2.9 个月至未达到），联合组为 4.2 个月（95%CI，2.8-8.3 个月）。单药帕唑帕尼组与联合组最常见的所有级别不良事件分别为疲劳（29 例[55%]与 37 例[61%]）、头痛（12 例[23%]与 39 例[64%]）、腹泻（27 例[51%]与 35 例[57%]）、恶心（26 例[49%]与 29 例[48%]）、呕吐（12 例[23%]与 23 例[38%]）、贫血（5 例[9%]与 27 例[44%]）、鼻出血（2 例[4%]与 34 例[56%]）和高血压（29 例[55%]与 22 例[36%]）。
在这项 3 期随机临床试验中，卡妥昔单抗联合帕唑帕尼与单独使用帕唑帕尼相比，并未改善晚期血管肉瘤患者的 PFS。
ClinicalTrials.gov 标识符：NCT02979899。
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