替雷利珠单抗联合化疗治疗Ⅲb~Ⅳ期非小细胞肺癌患者的临床研究

Clinical trial of tislelizumab combined with chemotherapy in the treatment of patients with stage Ⅲb-Ⅳ non-small cell lung cancer

目的 分析替雷利珠单抗联合化疗治疗Ⅲb~Ⅳ期非小细胞肺癌(NSCLC)的临床疗效及其对T淋巴细胞免疫、生存预后的影响。方法 将NSCLC患者按治疗方法不同分为对照组和试验组。对照组给予含铂双药联合化疗方案进行治疗,PC方案:第1天静脉滴注培美曲塞500 mg·m^(-2),第1天按血药浓度-时间曲线下面积(AUC)=5 mg·mL^(-1)·min^(-1)静脉滴注卡铂;TP方案:第1天静脉滴注紫杉醇135 mg·m^(-2),第1~3天按AUC=5 mg·mL^(-1)·min^(-1)静脉滴注卡铂。试验组在对照组治疗的基础上静脉输注替雷利珠单抗200 mg,每3周给药1次。3周为1个治疗周期,2组均治疗2个周期。比较2组患者的临床疗效、血清肿瘤标志物水平、T淋巴细胞免疫功能水平、无进展生存时间(PFS)和总生存时间(OS)以及治疗期间药物不良反应发生情况。结果 对照组和试验组各40例。治疗后,对照组和试验组的总有效率分别为40.00%(16例/40例)和62.50%(25例/40例),疾病控制率分别为70.00%(28例/40例)和90.00%(36例/40例),癌胚抗原(CEA)分别为(9.21±2.03)和(5.42±1.36)ng·mL^(-1),糖抗原125(CA125)分别为(72.53±8.16)和(31.95±5.08)U·mL^(-1),糖抗原19-9(CA19-9)分别为(25.79±3.31)和(10.38±2.04)U·mL^(-1),细胞角质蛋白19片段抗原21-1(CYFRA21-1)分别为(6.47±1.34)和(4.26±0.91)ng·mL^(-1),CD3^(+)分别为(54.36±5.81)%和(61.85±4.96)%,CD4^(+)分别为(31.28±2.93)%和(43.08±3.15)%,CD4^(+)/CD8^(+)分别为1.43±0.40和1.91±0.46,生存率分别为47.37%(18例/38例)和67.57%(25例/37例),PFS分别为7.73个月(95%CI:6.42~9.03)和9.75个月(95%CI:8.68~10.82),OS分别为8.96个月(95%CI:7.94~9.97)和10.52个月(95%CI:9.78~11.27),在统计学上差异均有统计学意义(均P<0.05)。2组患者的胃肠道反应、肝功能异常、骨髓抑制、甲状腺功能减退以及非感染性肺炎发生率比较,在统计学上差异均无统计学意义(均P>0.05)。结论 替雷利珠单抗联合化疗治疗Ⅲb~Ⅳ期NSCLC效果较好,可有效降低血清肿瘤标志物水平,改善患者T淋巴细胞免疫功能,并延长患者生存时间,安全性良好。

Objective To analyze the effect of tislelizumab combined with chemotherapy in the treatment of stageⅢb-Ⅳnon-small cell lung cancer (NSCLC) and its influence on T lymphocyte immunity and survival prognosis.Methods Patients with NSCLC were divided into control group and treatment group according to different treatment methods.The control group was treated with platinum-containing dual-drug combined chemotherapy regimen (PCregimen:intravenous drip of pemetrexed 500 mg·m^(-2)on the 1^(st)day and intravenous drip of carboplatin with area under plasma concentration-time curve (AUC)=5 mg·m L^(-1)·min^(-1)on the 1^(st)day;TP regimen:intravenous drip of taxol 135 mg·m^(-2)on the 1^(st)day,and intravenous drip of carboplatin with AUC=5 mg·m L^(-1)·min^(-1)on the 1^(st) day to 3^(rd)day).The treatment group was given tislelizumab 200 mg intravenously once every 3 weeks on the basis of the control group.Both groups were treated for 2 cycles by taking 3 weeks as 1 treatment cycle.The clinical efficacy,serum tumor markers levels,T lymphocyte immune function,progression-free survival (PFS) and overall survival(OS) and occurrence of adverse drug reactions during treatment were compared between the two groups.Results There were 40 cases in control group and 40 cases in treatment group.After treatment,the total effective rates in control group and treatment group were 40.00%(16 cases/40 cases) and 62.50%(25 cases/40 cases),the disease control rates were 70.00%(28 cases/40 cases) and 90.00%(36 cases/40 cases),carcinoembryonic antigen(CEA) levels were (9.21±2.03) and (5.42±1.36) ng·m L^(-1),carbohydrate antigen 125 (CA125) levels were(72.53±8.16) and (31.95±5.08) U·m L^(-1),carbohydrate antigen 19-9 (CA19-9) levels were(25.79±3.31) and (10.38±2.04) U·m L^(-1),cytokeratin19 fragment antigen 21-1 (CYFRA21-1) levels were(6.47±1.34) and (4.26±0.91) ng·m L^(-1),CD3~+levels were (54.36±5.81)%and (61.85±4.96)%,CD4^(+)levels were (31.28±2.93)%and (43.08±3.15)%,CD4^(+)/CD8^(+)were 1.43±0.40 and 1.91±0.46,survival rates were 47.37%(18 cases/38 cases) and 67.57%(25 cases/37 cases),PFS were 7.73 months (95%CI:6.42-9.03) and 9.75 months (95%CI:8.68-10.82),and OS were 8.96 months (95%CI:7.94-9.97) and10.52 months (95%CI:9.78-11.27) respectively (all P<0.05).There were no statistically significant differences in the incidence of gastrointestinal reactions,liver dysfunction,bone marrow suppression,hypothyroidism and noninfectious pneumonia between both groups (all P>0.05).Conclusion Tislelizumab combined with chemotherapy has a good effect in the treatment of stageⅢb-ⅣNSCLC,and it can effectively reduce the levels of serum tumor markers,improve the T lymphocyte immune function,and prolong the survival time of patients,with good safety.