Department of Medicine, Division of Oncology, Sylvester Comprehensive Cancer Center at University of Miami Miller School of Medicine, 1475 NW 12th Avenue, Miami, FL, 33136, USA.
Agenus Inc., 3 Forbes Road, Lexington, MA, 02421, USA.
J Immunother Cancer. 2019 Aug 8;7(1):213. doi: 10.1186/s40425-019-0689-7.
Angiosarcoma is an uncommon endothelial malignancy and a highly aggressive soft tissue sarcoma. Due to its infiltrative nature, successful management of localized angiosarcoma is often challenging. Systemic chemotherapy is used in the metastatic setting and occasionally in patients with high-risk localized disease in neoadjuvant or adjuvant settings. However, responses tend to be short-lived and most patients succumb to metastatic disease. Novel therapies are needed for patients with angiosarcomas.
We performed a retrospective analysis of patients with locally advanced or metastatic angiosarcoma, who were treated with checkpoint inhibitors at our institution. We collected their clinical information and outcome measurements. In one patient with achieved complete response, we analyzed circulating and infiltrating T cells within peripheral blood and tumor tissue.
We have treated seven angiosarcoma (AS) patients with checkpoint inhibitors either in the context of clinical trials or off label [Pembrolizumab + Axitinib (NCT02636725; n = 1), AGEN1884, a CTLA-4 inhibitor (NCT02694822; n = 2), Pembrolizumab (n = 4)]. Five patients had cutaneous angiosarcoma, one primary breast angiosarcoma and one radiation-associated breast angiosarcoma. At 12 weeks, 5/7 patients (71%) had partial response of their lesions either on imaging and/or clinical exam and two (29%) had progressive disease. 6/7 patients are alive to date and, thus far, 3/7 patients (43%) have progressed (median 3.4 months)- one achieved partial response after pembrolizumab was switched to ongoing Nivolumab/Ipilimumab, one died of progressive disease at 31 weeks (primary breast angiosarcoma) and one was placed on pazopanib. One patient had a complete response (CR) following extended treatment with monotherapy AGEN1884. No patient experienced any ≥ grade 2 toxicities.
This case series underscores the value of targeted immunotherapy in treating angiosarcoma. It also identifies genetic heterogeneity of cutaneous angiosarcomas and discusses specific genetic findings that may explain reported benefits from immunotherapy.
血管肉瘤是一种罕见的内皮恶性肿瘤，也是一种高度侵袭性的软组织肉瘤。由于其浸润性，局部血管肉瘤的成功治疗常常具有挑战性。系统化疗用于转移性疾病，偶尔也用于新辅助或辅助治疗高危局部疾病的患者。然而，这些反应往往是短暂的，大多数患者最终死于转移性疾病。需要为血管肉瘤患者提供新的治疗方法。
我们对在我院接受检查点抑制剂治疗的局部晚期或转移性血管肉瘤患者进行了回顾性分析。我们收集了他们的临床信息和结果测量数据。在一名完全缓解的患者中，我们分析了外周血和肿瘤组织中循环和浸润的 T 细胞。
我们用检查点抑制剂治疗了 7 名血管肉瘤（AS）患者，其中包括临床试验或非标签药物治疗[Pembrolizumab+Axitinib（NCT02636725；n=1），AGEN1884，一种 CTLA-4 抑制剂（NCT02694822；n=2），Pembrolizumab（n=4）]。5 名患者患有皮肤血管肉瘤，1 名患有原发性乳腺血管肉瘤，1 名患有放射相关性乳腺血管肉瘤。在 12 周时，7 名患者中有 5 名（71%）的病变在影像学和/或临床检查中出现部分缓解，2 名（29%）出现疾病进展。到目前为止，7 名患者中有 6 名仍然存活，到目前为止，7 名患者中有 3 名（43%）已经进展（中位时间 3.4 个月）-1 名患者在将 Pembrolizumab 转换为持续的 Nivolumab/Ipilimumab 后出现部分缓解，1 名患者在 31 周时因疾病进展而死亡（原发性乳腺血管肉瘤），1 名患者接受 Pazopanib 治疗。1 名患者在接受 AGEN1884 单药治疗延长后获得完全缓解（CR）。没有患者出现任何≥2 级毒性。
本病例系列强调了靶向免疫疗法在治疗血管肉瘤中的价值。它还确定了皮肤血管肉瘤的遗传异质性，并讨论了可能解释报告的免疫治疗益处的特定遗传发现。
