Abstract：
BACKGROUND: There is increasing evidence that combination therapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) and programmed cell death protein 1 (PD-1) inhibitor is safe and efficacious in treating many types of malignant tumors. However, clinical data demonstrating the effect of this treatment combination for patients with metastatic soft tissue sarcoma (STS) are currently limited.
METHODS: The clinical data of patients with metastatic STS who received nab-paclitaxel plus PD-1 inhibitor (sintilimab) therapy between January 2019 and February 2021 were retrospectively analyzed. The effectiveness and safety of the combined treatment were evaluated in terms of the median progression-free survival (PFS), estimated using the Kaplan-Meier method. The univariate Cox proportional hazards model was used to analyze the relationship between clinicopathological parameters and PFS. All statistical analyses were two-sided; P < 0.05 was considered statistically significant.
RESULTS: A total of 28 patients treated with nab-paclitaxel plus sintilimab were enrolled in this study. The objective response rate was 25%, the disease control rate was 50%, and the median PFS was 2.25 months (95% CI = 1.8-3.0 months). The most common grade 1 or 2 adverse events (AEs) were alopecia (89.3%; 25/28), leukopenia (25.0%; 7/28), fatigue (21.4%; 6/28), anemia (21.4%; 6/28), and nausea (21.4%; 6/28). The most common grade 3 AEs were neutropenia (10.7%; 3/28) and peripheral neuropathy (10.7%; 3/28). No grade 4 AEs were observed. Among the present study cohort, patients with angiosarcoma (n = 5) had significantly longer PFS (P = 0.012) than patients with other pathological subtypes, including undifferentiated pleomorphic sarcoma (n = 7), epithelioid sarcoma (n = 5), fibrosarcoma (n = 4), synovial sarcoma (n = 3), leiomyosarcoma (n = 2), pleomorphic liposarcoma (n = 1), and rhabdomyosarcoma (n = 1); those who experienced three or more AEs had significantly longer median PFS than those who experienced less than three AEs (P = 0.018).
CONCLUSIONS: Nab-paclitaxel plus PD-1 inhibitor is a promising treatment regimen for advanced STS. Randomized controlled clinical trials are required to further demonstrate its efficacy and optimal application scenario.
METHODS: The clinical data of patients with metastatic STS who received nab-paclitaxel plus PD-1 inhibitor (sintilimab) therapy between January 2019 and February 2021 were retrospectively analyzed. The effectiveness and safety of the combined treatment were evaluated in terms of the median progression-free survival (PFS), estimated using the Kaplan-Meier method. The univariate Cox proportional hazards model was used to analyze the relationship between clinicopathological parameters and PFS. All statistical analyses were two-sided; P < 0.05 was considered statistically significant.
RESULTS: A total of 28 patients treated with nab-paclitaxel plus sintilimab were enrolled in this study. The objective response rate was 25%, the disease control rate was 50%, and the median PFS was 2.25 months (95% CI = 1.8-3.0 months). The most common grade 1 or 2 adverse events (AEs) were alopecia (89.3%; 25/28), leukopenia (25.0%; 7/28), fatigue (21.4%; 6/28), anemia (21.4%; 6/28), and nausea (21.4%; 6/28). The most common grade 3 AEs were neutropenia (10.7%; 3/28) and peripheral neuropathy (10.7%; 3/28). No grade 4 AEs were observed. Among the present study cohort, patients with angiosarcoma (n = 5) had significantly longer PFS (P = 0.012) than patients with other pathological subtypes, including undifferentiated pleomorphic sarcoma (n = 7), epithelioid sarcoma (n = 5), fibrosarcoma (n = 4), synovial sarcoma (n = 3), leiomyosarcoma (n = 2), pleomorphic liposarcoma (n = 1), and rhabdomyosarcoma (n = 1); those who experienced three or more AEs had significantly longer median PFS than those who experienced less than three AEs (P = 0.018).
CONCLUSIONS: Nab-paclitaxel plus PD-1 inhibitor is a promising treatment regimen for advanced STS. Randomized controlled clinical trials are required to further demonstrate its efficacy and optimal application scenario.
摘要：
背景：越来越多的证据表明，纳米颗粒白蛋白结合型紫杉醇（nab-pacytaxel）和程序性细胞死亡蛋白1（PD-1）抑制剂的联合治疗在治疗许多类型的恶性肿瘤中是安全有效的。然而,目前,证实这种联合治疗对转移性软组织肉瘤(STS)患者疗效的临床数据有限.
方法：回顾性分析2019年1月至2021年2月接受nab-紫杉醇联合PD-1抑制剂(sintilimab)治疗的转移性STS患者的临床资料。根据中位无进展生存期（PFS）评估联合治疗的有效性和安全性，使用卡普兰-迈耶方法估计。采用单因素Cox比例风险模型分析临床病理参数与PFS的关系。所有统计分析都是双侧的;P<0.05被认为具有统计学意义。
结果：本研究共纳入28例接受nab-紫杉醇联合sintilimab治疗的患者。客观反应率为25%，疾病控制率为50%，中位PFS为2.25个月（95%CI=1.8-3.0个月）。最常见的1级或2级不良事件（AE）是脱发（89.3％;25/28），白细胞减少症（25.0%；7/28），疲劳（21.4%；6/28），贫血（21.4%；6/28），恶心（21.4%；6/28）。最常见的3级AE是中性粒细胞减少症(10.7%;3/28)和周围神经病变(10.7%;3/28)。没有观察到4级AE。在目前的研究队列中，血管肉瘤患者（n=5）的PFS明显长于其他病理亚型患者（P=0.012），包括未分化多形性肉瘤（n=7），上皮样肉瘤（n=5），纤维肉瘤（n=4），滑膜肉瘤（n=3），平滑肌肉瘤（n=2），多形性脂肪肉瘤（n=1），和横纹肌肉瘤(n=1);经历3次或3次以上AE的患者的中位PFS明显长于经历3次以下AE的患者(P=0.018).
结论：Nab-紫杉醇联合PD-1抑制剂是治疗晚期STS的一种有希望的治疗方案。需要随机对照临床试验来进一步证明其疗效和最佳应用方案。
方法：回顾性分析2019年1月至2021年2月接受nab-紫杉醇联合PD-1抑制剂(sintilimab)治疗的转移性STS患者的临床资料。根据中位无进展生存期（PFS）评估联合治疗的有效性和安全性，使用卡普兰-迈耶方法估计。采用单因素Cox比例风险模型分析临床病理参数与PFS的关系。所有统计分析都是双侧的;P<0.05被认为具有统计学意义。
结果：本研究共纳入28例接受nab-紫杉醇联合sintilimab治疗的患者。客观反应率为25%，疾病控制率为50%，中位PFS为2.25个月（95%CI=1.8-3.0个月）。最常见的1级或2级不良事件（AE）是脱发（89.3％;25/28），白细胞减少症（25.0%；7/28），疲劳（21.4%；6/28），贫血（21.4%；6/28），恶心（21.4%；6/28）。最常见的3级AE是中性粒细胞减少症(10.7%;3/28)和周围神经病变(10.7%;3/28)。没有观察到4级AE。在目前的研究队列中，血管肉瘤患者（n=5）的PFS明显长于其他病理亚型患者（P=0.012），包括未分化多形性肉瘤（n=7），上皮样肉瘤（n=5），纤维肉瘤（n=4），滑膜肉瘤（n=3），平滑肌肉瘤（n=2），多形性脂肪肉瘤（n=1），和横纹肌肉瘤(n=1);经历3次或3次以上AE的患者的中位PFS明显长于经历3次以下AE的患者(P=0.018).
结论：Nab-紫杉醇联合PD-1抑制剂是治疗晚期STS的一种有希望的治疗方案。需要随机对照临床试验来进一步证明其疗效和最佳应用方案。
