PD-1抑制剂联合抗血管生成治疗晚期三阴性乳腺癌患者临床疗效及预后分析

Clinical efficacy and prognosis of PD-1 inhibitor combined with anti-angiogenic therapy in patients with advanced triple-negative breast cancer

目的探究PD-1抑制剂卡瑞丽珠单抗联合VEGFR2抑制剂阿帕替尼治疗晚期三阴性乳腺癌(TNBC)患者的临床疗效和预后分析。方法纳入2019年12月至2021年12月期间沧州市中心医院收治的82例晚期三阴性乳腺癌患者,按照治疗方法分为观察组(n=41)和对照组(n=41)。在白蛋白紫杉醇常规治疗260 mg/m 2,d1,21 d为1个治疗周期,连续使用4个周期的基础上,对照组加卡瑞丽珠单抗治疗200 mg/次,21 d为一个周期,连续使用4个周期;观察组采用卡瑞丽珠单抗200 mg/次,21 d为一个周期,连续使用4个周期,联合阿帕替尼治疗250 mg/次进行口服,1日/次,28 d为1个治疗周期,持续使用3个周期。并从接受治疗开始对两组患者进行为期1年的随访。观察两组的客观缓解率(ORR)、疾病控制率(DCR)、无进展生存期(PFS)和总生存期(OS),并比较治疗前后两组的肿瘤标志物水平(CEA、CA153、CA125)、免疫相关指标(T细胞绝对值计数)、预后指标(TK1、VEGF、MUC1、CD44v6)以及不良反应的发生情况。其中主要结局指标为ORR及OS,其余为次要结局指标。结果对两组临床疗效进行评估显示,观察组患者的ORR(48.8%)和DCR(73.2%)均优于对照组(分别为24.4%和46.3%),差异具有统计学意义(P<0.05);观察组和对照组的中位PFS分别为6.80个月(95%CI:6.17~7.43)和4.70个月(95%CI:3.32~6.08),观察组相对于对照组进展的风险比HR为0.537(95%CI:0.337~0.857);观察组和对照组的中位OS分别为10.90个月(95%CI:9.39~12.41)和7.60个月(95%CI:6.97~8.23),观察组相对于对照组死亡的风险比HR为0.406(95%CI:0.241~0.684);观察组的PFS和OS均长于对照组(P<0.05);观察组肿瘤标志物CEA、CA153水平均低于对照组(P<0.001);两组CA125水平及TK1水平差异无统计学意义(P>0.05);观察组VEGF、MUC1、CD44v6水平比对照组低(P<0.001);观察组T细胞绝对值计数高于对照组(P<0.05)。结论PD-1抑制剂卡瑞丽珠单抗联合VEGFR2抑制剂阿帕替尼治疗晚期TNBC患者,临床疗效较为可观,使患者的预后和免疫功能得到了改善,并且安全性相对可控。

Objective This study aims to explore the clinical efficacy and prognostic analysis of PD-1 inhibitor Camrelizumab in combination with VEGFR2 inhibitor Apatinib in the treatment of patients with advanced triple-negative breast cancer(TNBC).Methods The study included 82 patients with advanced TNBC admitted to Cangzhou Central Hospital from December 2019 to December 2021,who were divided into an observation group(n=41)and a control group(n=41).In addition to the standard treatment with albumin-bound paclitaxel(260 mg/m 2,day 1,every 21 days for 4 cycles),the control group received Camrelizumab(200 mg per cycle,every 21 days for 4 cycles);while the observation group was treated with the same regimen of Camrelizumab plus oral Apatinib(250 mg daily,28-day cycle for 3 cycles).A one-year follow-up was conducted from the start of treatment.The study compared objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),and overall survival(OS)between the groups,alongside pre-and post-treatment levels of tumor markers(CEA,CA153,CA125),immune-related indicators(absolute T-cell counts),prognostic indicators(TK1,VEGF,MUC1,CD44v6),and the incidence of adverse reactions.Primary outcomes were ORR and OS,with the rest as secondary outcomes.Results Clinical efficacy assessment showed that the observation group had significantly higher ORR(48.8%)and DCR(73.2%)compared to the control group(24.4%and 46.3%,respectively;P<0.05).The median PFS was 6.80 months(95%CI:6.17-7.43)in the observation group and 4.70 months(95%CI:3.32-6.08)in the control group,with the observation group showing a lower risk of progression(HR=0.537,95%CI:0.337~0.857).The median OS was 10.90 months(95%CI:9.39~12.41)in the observation group and 7.60 months(95%CI:6.97~8.23)in the control group,with the observation group exhibiting a lower risk of death(HR=0.406,95%CI:0.241-0.684).The observation group had significantly longer PFS and OS(P<0.05),lower levels of tumor markers(CEA,CA153)(P<0.001),and lower levels of VEGF,MUC1,CD44v6(P<0.001),but no significant difference in CA125 and TK1 levels(P>0.05).The observation group also showed higher absolute T-cell counts(P<0.05).Conclusions The combined therapy of PD-1 inhibitor Camrelizumab and VEGFR2 inhibitor Apatinib in advanced TNBC patients demonstrates considerable clinical efficacy,improving prognosis and immune function with a manageable safety profile.