Purpose: Doxorubicin is standard therapy for advanced soft-tissue sarcoma (STS) with minimal improvement in efficacy and increased toxicity with addition of other cytotoxic agents. Pembrolizumab monotherapy has demonstrated modest activity and tolerability in previous advanced STS studies. This study combined pembrolizumab with doxorubicin to assess safety and efficacy in frontline and relapsed settings of advanced STS. Patients and Methods: This single-center, single-arm, phase II trial enrolled patients with unresectable or metastatic STS with no prior anthracycline therapy. Patients received pembrolizumab 200 mg i.v. and doxorubicin (60 mg/m2 cycle 1 with subsequent escalation to 75 mg/m2 as tolerated). The primary endpoint was safety. Secondary endpoints included overall survival (OS), objective response rate (ORR), and progression-free survival (PFS) based on RECIST v1.1 guidelines. Results: Thirty patients were enrolled (53.3% female; median age 61.5 years; 87% previously untreated) with 4 (13.3%) patients continuing treatment. The study met its primary safety endpoint by prespecified Bayesian stopping rules. The majority of grade 3+ treatment-emergent adverse events were hematologic (36.7% 3+ neutropenia). ORR was 36.7% [95% confidence interval (CI), 19.9–56.1%], with documented disease control in 80.0% (95% CI, 61.4–92.3%) of patients. Ten (33.3%) patients achieved partial response, 1 (3.3%) patient achieved complete response, and 13 (43.3%) patients had stable disease. Median PFS and OS were 5.7 months (6-month PFS rate: 44%) and 17 months (12-month OS rate: 62%), respectively. Programmed cell death ligand-1 (PD-L1) expression was associated with improved ORR, but not OS or PFS. Conclusions: Combination pembrolizumab and doxorubicin has manageable toxicity and preliminary promising activity in treatment of patients with anthracycline-naive advanced STS.

中文翻译：

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派姆单抗联合阿霉素治疗转移性和不可切除软组织肉瘤的 II 期研究

目的：多柔比星是晚期软组织肉瘤 (STS) 的标准疗法，在添加其他细胞毒剂后，疗效改善甚微，毒性增加。在先前的高级 STS 研究中，派姆单抗单药治疗已证明具有适度的活性和耐受性。本研究将派姆单抗与多柔比星相结合，以评估在晚期 STS 的一线和复发环境中的安全性和有效性。患者和方法：这项单中心、单臂、II 期试验纳入了既往未接受过蒽环类药物治疗的不可切除或转移性 STS 患者。患者接受了派姆单抗 200 mg iv 和多柔比星（60 mg/m2 第 1 周期，随后在耐受情况下增加至 75 mg/m2）。主要终点是安全性。次要终点包括总生存期（OS）、客观缓解率（ORR）、和基于 RECIST v1.1 指南的无进展生存期 (PFS)。结果：30 名患者入组（53.3% 为女性；中位年龄 61.5 岁；87% 以前未治疗），其中 4 名（13.3%）患者继续治疗。该研究通过预先指定的贝叶斯停止规则达到了其主要安全终点。大多数 3+ 级治疗出现的不良事件是血液系统的（36.7% 3+ 中性粒细胞减少症）。ORR 为 36.7% [95% 置信区间 (CI), 19.9–56.1%]，80.0% (95% CI, 61.4–92.3%) 的患者有记录的疾病控制。10例（33.3%）患者达到部分缓解，1例（3.3%）患者达到完全缓解，13例（43.3%）患者病情稳定。中位 PFS 和 OS 分别为 5.7 个月（6 个月 PFS 率：44%）和 17 个月（12 个月 OS 率：62%）。程序性细胞死亡配体 1 (PD-L1) 表达与改善的 ORR 相关，但与 OS 或 PFS 无关。结论：帕博利珠单抗和多柔比星联合用药在治疗未接受过蒽环类药物治疗的晚期 STS 患者中具有可控的毒性和初步有希望的活性。