免疫检查点抑制剂治疗复发转移性宫颈癌的疗效及预后分析

Analysis of curative effect and prognosis of immune checkpoint inhibitor in the treatment of recurrent and metastatic cervical cancer

目的分析免疫检查点抑制剂治疗复发转移性宫颈癌的疗效、安全性及其预后影响因素。方法回顾性分析2018年1月至2022年6月苏州大学附属第一医院收治的87例复发转移性宫颈癌患者,根据复发转移后是否应用免疫检查点抑制剂将患者分为非免疫治疗组(n=32)及免疫治疗组(n=55)。比较两组患者的疾病控制率(DCR)、无进展生存期(PFS)、总生存期1(OS1,病理确诊日期至随访截止时间或患者死亡时间)、总生存期2(OS2,首次免疫治疗/非免疫治疗时间至随访截止时间或患者死亡时间)、安全性及影响预后的因素。结果非免疫治疗组与免疫治疗组的DCR分别为53.1%(17/32)和72.7%(40/55),差异无统计学意义(χ^(2)=3.44,P=0.064)。非免疫治疗组中位OS1为51.0个月,免疫治疗组未达到中位OS1,差异有统计学意义(χ^(2)=7.50,P=0.006);非免疫治疗组中位OS2为28.0个月,免疫治疗组未达到中位OS2,差异有统计学意义(χ^(2)=7.07,P=0.008)。非免疫治疗组与免疫治疗组的中位PFS分别为18.0个月和23.0个月,差异无统计学意义(χ^(2)=0.01,P=0.915)。在免疫治疗组中,接受免疫检查点抑制剂作为一线治疗的患者占70.9%(39/55),作为二线及以上治疗的患者占29.1%(16/55),患者均未达到中位OS2,中位PFS分别为23.0个月和17.0个月,差异均无统计学意义(χ^(2)=0.94,P=0.333;χ^(2)=2.00,P=0.158);38.2%(21/55)的患者接受免疫检查点抑制剂联合局部放疗,61.8%(34/55)的患者未行放疗,患者均未达到中位OS2,中位PFS分别为19.0个月和25.0个月,差异均无统计学意义(χ^(2)=0.62,P=0.432;χ^(2)=0.01,P=0.906)。非免疫治疗组与免疫治疗组用药期间1~2级血尿及甲状腺功能减退发生率分别为53.1%(17/32)比27.3%(15/55)、3.1%(1/32)比21.8%(12/55),差异均有统计学意义(χ^(2)=5.82,P=0.016;χ^(2)=4.19,P=0.041);非免疫治疗组骨髓抑制的发生率[1~2级为59.4%(19/32),3~4级为34.4%(11/32)]与免疫治疗组[1~2级为80.0%(44/55),3~4级为3.6%(2/55)]差异有统计学意义(Z=3.50,P<0.001);肌酐升高、谷草转氨酶及谷丙转氨酶升高、淋巴细胞降低、低蛋白血症、蛋白尿、皮疹、乏力发生率的差异均无统计学意义(均P>0.05)。单因素回归分析显示,免疫检查点抑制剂的应用是患者预后的独立保护因素(HR=0.31,95%CI为0.12~0.77,P=0.012)。结论无论作为一线或二线及以上治疗,复发转移性宫颈癌患者应用免疫检查点抑制剂延长了患者的OS1、OS2,并具有良好的安全性。免疫检查点抑制剂的应用是患者预后的独立保护因素。

Objective To analyze the efficacy,safety and prognostic factors of immune checkpoint inhibitors in the treatment of recurrent and metastatic cervical cancer.Methods A total of 87 patients with recurrent and metastatic cervical cancer admitted to the First Affiliated Hospital of Soochow University from January 2018 to June 2022 were retrospectively analyzed.They were divided into non immunotherapy group(n=32)and immunotherapy group(n=55)according to whether immune checkpoint inhibition was applied after recurrence and metastasis.The disease control rate(DCR),progression free survival(PFS),overall survival 1(OS1,date of pathology diagnosis to the end of follow-up or time of death),overall survival 2(OS2,time of first immunotherapy/non-immunotherapy to the end of follow-up or time of death),safety and prognostic factors of the two groups were analyzed and compared.Results In 87 patients with recurrent and metastatic cervical cancer,the DCR of the non immunotherapy group and immunotherapy group were 53.1%(17/32)and 72.7%(40/55)respectively(χ^(2)=3.44,P=0.064).The median OS1 of the non immunotherapy group was 51.0 months,while the immunotherapy group did not reach the median OS1,with a statistically significant difference(χ^(2)=7.50,P=0.006).The median OS2 of the non immunotherapy group was 28.0 months,while the immunotherapy group did not reach the median OS2,with a statistically significant difference(χ^(2)=7.07,P=0.008).The median PFS of the non immunotherapy group and immunotherapy group were 18.0 months and 23.0 months respectively,with no significant difference(χ^(2)=0.01,P=0.915).In the immunotherapy group,70.9%(39/55)of patients received immune checkpoint inhibitors as first-line treatment and 29.1%(16/55)received as second-line and above treatment.Both groups of patients did not achieve median OS2,with median PFS of 23.0 and 17.0 months respectively,and there were no statistically significant differences(χ^(2)=0.94,P=0.333;χ^(2)=2.00,P=0.158);38.2%(21/55)of patients received immune checkpoint inhibitor combined with local radiotherapy,61.8%(34/55)patients did not receive radiotherapy.And neither group of patients achieved median OS2,with median PFS of 19.0 and 25.0 months respectively,with no statistically significant differences(χ^(2)=0.62,P=0.432;χ^(2)=0.01,P=0.906).The incidences of grade 1-2 hematuria and hypothyroidism in the non immunotherapy group and immunotherapy group were 53.1%(17/32)vs.27.3%(15/55,χ^(2)=5.82,P=0.016),3.1%(1/32)vs.21.8%(12/55,χ^(2)=4.19,P=0.041)respectively.The incidence of myelosuppression in the non immunotherapy group[grade 1-2:59.4%(19/32),grade 3-4:34.4%(11/32)]was significantly different from that in the immunotherapy group[grade 1-2:80.0%(44/55),grade 3-4:3.6%(2/55);Z=3.50,P<0.001].There were no statistically significant differences between creatinine increase,glutamicoxaloacetic transaminase and glutamic-pyruvic transaminase increase,lymphocyte decrease,hypoproteinemia,proteinuria,rash,fatigue(all P>0.05).Univariate regression analysis showed that the use of immune checkpoint inhibitor was an independent protective factor affecting the prognosis of patients(HR=0.31,95%CI:0.12-0.77,P=0.012).Conclusion Whether used as first-line or second-line or above treatment,the use of immune checkpoint inhibitors in patients with recurrent and metastatic cervical cancer prolongs their OS1,OS2,and has good safety.The application of immune checkpoint inhibitors is an independent protective factor affecting the prognosis of patients.