化疗联合程序性细胞死亡受体1抗体和安罗替尼对晚期去分化脂肪肉瘤的疗效及其安全性

Efficacy and safety of combination therapy with chemotherapy,programmed death-1 inhibitor and anlotinib in the treatment of advanced dedifferentiated liposarcoma

目的探讨化疗联合程序性细胞死亡受体1(PD-1)抗体和安罗替尼对晚期去分化脂肪肉瘤的疗效及安全性。方法回顾性分析2020年1月1日至2021年11月30日在复旦大学附属中山医院肿瘤内科接受化疗联合免疫PD-1抗体和安罗替尼治疗的去分化脂肪肉瘤患者的临床资料,共24例患者纳入研究,其中男12例,女12例,中位发病年龄56岁(31~69岁)。分析其疗效和安全性。结果患者均为肿瘤病理简明三级分级方案中G2(中分化)或G3(差分化)的不可切除或转移性去分化脂肪肉瘤。一线治疗12例,二线治疗7例,三线及以上治疗5例。中位随访时间7.7个月,客观缓解率为20.8%(5/24),疾病控制率为83.3%(20/24),5例部分缓解,15例疾病稳定,4例进展。24例患者中位无进展生存期为4.9个月(95%CI:3.4~16.2个月)。以蒽环类药物、艾立布林或吉西他滨为基础的联合治疗的客观缓解率分别为1/12、2/6和2/6,中位无进展生存期分别为7.7、7.3和4.4个月。瀑布图显示蒽环类为基础治疗患者更多表现为疾病稳定(9/12),而艾立布林和吉西他滨为基础治疗更多出现缩瘤(3/6和2/6)。常见不良反应有骨髓抑制、乏力、纳差、皮疹、皮肤瘙痒、心悸、甲状腺功能减退、高血压等。结论化疗联合PD-1抗体和安罗替尼治疗晚期去分化脂肪肉瘤疗效确切,不良反应可耐受。艾立布林和吉西他滨为基础的联合治疗缩瘤效果更佳。

Objective To investigate the efficacy and safety of the combination therapy with chemotherapy,programmed death-1(PD-1)inhibitor and anlotinib in the treatment of advanced dedifferentiated liposarcoma(DDLPS).Methods The clinical data of patients with dedifferentiated liposarcoma who received chemotherapy combined with PD-1 inhibitor and anlotinib in the Department of Medical Oncology,Zhongshan Hospital Affiliated to Fudan University from January 1,2020 to November 30,2021 were retrospectively analyzed.A total of 24 patients were included in this study,including 12 males and 12 females,with a median age of onset of 56 years(range,31-69 years).Efficacy and safety in those patients were assessed.Results All patients had unresectable or metastatic dedifferentiated liposarcoma with G2(moderate differentiation)or G3(differential differentiation)in a concise three-grade grading scheme of tumor pathology.Twelve patients received the regimen as the first-line treatment,while the other 7 taken the regimen as second-line treatment and 5 as third-line or above.The median follow-up time for overall survival(OS)was 7.7 months.The overall response rate(ORR)was 20.8%(5/24)and disease control rate(DCR)was 83.3%(20/24)with 5 partial response(PR),15 stable disease(SD)and 4 progressive disease(PD).Overall,the median progression-free survival(PFS)was 4.9 months(95%CI:3.4-16.2 months).The ORR of anthracycline-based,eribulin-based or gemcitabine-based regimens was 1/12,2/6 and 2/6,respectively;and the median PFS was 7.7,7.3 and 4.4 months,respectively.Waterfall plots showed notable tumor shrinkage of any degree in eribulin and gemcitabine-based regimens(3/6 and 2/6,respectively),while there were more patients presented with SD in anthracycline-based group(9/12).Common adverse reactions included myelosuppression,fatigue,anorexia,rash,pruritus,palpitate,hypothyroidism and hypertension.Conclusions The combination regimen with chemotherapy,PD-1 inhibitor and anlotinib in the treatment of advanced DDLPS is effective and well tolerable.There are more responders in eribulin or gemcitabine-based regimens.