Departments of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Pressler St., FCT17.6054, Unit 1484, Houston, TX, 77030, USA.
Departments of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
BMC Cancer. 2018 Sep 24;18(1):913. doi: 10.1186/s12885-018-4829-0.
Soft tissue sarcomas are a heterogeneous and rare group of solid tumors of mesenchymal origin that can arise anywhere in the body. Although surgical resection is the mainstay of treatment for patients with localized disease, disease recurrence is common and 5-year overall survival is poor (~ 65%). Both radiation therapy and conventional chemotherapy are used to reduce local and distant recurrence. However, the utility of radiation therapy is often limited by disease location (in the case of retroperitoneal sarcomas, for instance) while systemic therapy with conventional lines of chemotherapy offer limited efficacy and are often poorly tolerated and associated with significant toxicity. Within the past decade, major advances have been made in the treatment of other malignancies including melanoma, renal cell carcinoma, and non-small cell lung carcinoma with the advent of immune-checkpoint inhibitors such as ipilimumab (anti-CTLA4), pembrolizumab (anti-PD1), and nivolumab (anti-PD1). The recently published SARC028 (NCT02301039), an open label, phase II, multicenter trial of pembrolizumab in patients with advanced bone and soft tissue sarcomas reported promising activity in select histologic subtypes of advanced STS, including undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma.
There is a clear need for novel and effective adjuncts in the treatment of STS. We hypothesize that immune checkpoint blockade will be effective in patients with surgically resectable primary or locally recurrent dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma when administered in the neoadjuvant setting. The primary aim of this phase II, single-center, open label, randomized non-comparative trial is to determine the pathologic response to neoadjuvant nivolumab monotherapy and combination nivolumab/ipilimumab in patients with resectable dedifferentiated liposarcoma of the retroperitoneum or undifferentiated pleomorphic sarcoma of the trunk or extremity treated with concurrent standard of care neoadjuvant radiation therapy.
This study will help define the role of single agent anti-PD1 and combination anti-CTLA4 and anti-PD1 therapy in patients with surgically resectable dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma.
ClinicalTrials.gov NCT03307616 , registered October 12, 2017.
软组织肉瘤是一种起源于间充质的异质性和罕见的实体肿瘤，可发生于身体的任何部位。虽然手术切除是治疗局限性疾病患者的主要方法，但疾病复发很常见，5 年总生存率较差（约 65%）。放疗和常规化疗都被用于降低局部和远处复发的风险。然而，由于疾病部位的限制（例如腹膜后肉瘤），放疗的应用往往受到限制，而常规化疗方案的全身治疗疗效有限，且往往耐受性差，毒性大。在过去的十年中，随着免疫检查点抑制剂（如 ipilimumab[抗 CTLA4]、pembrolizumab[抗 PD1]和 nivolumab[抗 PD1]）的出现，黑色素瘤、肾细胞癌和非小细胞肺癌等其他恶性肿瘤的治疗取得了重大进展。最近发表的 SARC028（NCT02301039）是一项开放标签、二期、多中心 pembrolizumab 治疗晚期骨和软组织肉瘤患者的试验，报告了在晚期 STS 的某些组织学亚型中具有有前景的活性，包括未分化多形性肉瘤和去分化脂肪肉瘤。
在 STS 的治疗中，显然需要新的、有效的辅助治疗方法。我们假设，当免疫检查点阻断剂被用于新辅助治疗时，在手术可切除的原发性或局部复发性去分化脂肪肉瘤和未分化多形性肉瘤患者中是有效的。这项二期、单中心、开放标签、随机非对照试验的主要目的是确定新辅助 nivolumab 单药治疗和联合 nivolumab/ipilimumab 治疗同时接受标准新辅助放疗的可切除腹膜后去分化脂肪肉瘤或躯干或四肢未分化多形性肉瘤患者的病理反应。
这项研究将有助于确定单药抗 PD1 和联合抗 CTLA4 和抗 PD1 治疗在手术可切除的去分化脂肪肉瘤和未分化多形性肉瘤患者中的作用。
ClinicalTrials.gov NCT03307616，注册于 2017 年 10 月 12 日。
