复发性宫颈癌免疫治疗进展后挽救性治疗的临床意义

The clinical significance of salvage therapy in patients with recurrent cervical cancer after prior immunotherapy

目的:探索复发性宫颈癌免疫检查点抑制剂治疗进展后接受挽救性治疗患者的预后,并分析不同挽救性治疗方案的效果。方法:收集2018年2月1日至2022年12月31日于湖南省肿瘤医院就诊的使用免疫检查点抑制剂后进展的宫颈癌患者的临床病理资料及随访情况,将患者分为治疗组:免疫治疗进展后接受化疗±贝伐珠单抗(Chemo组)、化疗±贝伐珠单抗+免疫检查点抑制剂(Chemo+ICIs组)、免疫检查点抑制剂+酪氨酸激酶抑制剂(ICIs+TKIs组)。对照组:免疫进展后患者未进一步抗肿瘤治疗。观察两组患者的无进展生存期-1(PFS-1)、总生存期-1(OS-1),治疗组患者的无进展生存期-2(PFS-2)及总生存期-2(OS-2),以及不同挽救性治疗方案治疗的PFS-2和OS-2。结果:共有65例纳入治疗组,69例纳入对照组。治疗组和对照组的中位PFS-1分别为4.9月及4.9月,两组比较差异无统计学意义(P=0.904)。治疗组及对照组分别死亡28例及52例,中位OS-1分别为22.7个月和10.9个月,两组比较差异有统计学意义(P=0.000)。治疗组的中位PFS-2和OS-2分别为5.7月和14月,治疗组不同挽救性治疗方案Chemo组、Chemo+ICIs组、ICIs+TKIs组的PFS-2分别为4.5、7.0月和5.1月,差异均无统计学意义;中位OS-2分别为14.7、19个月和6.9个月,Chemo+ICIs组和ICIs+TKIs组的中位OS-2比较差异有统计学意义(P=0.029)。但联合化疗不良反应发生率虽较高,但差异无统计学意义。结论:复发性宫颈癌患者免疫治疗进展后,接受挽救性治疗可延长患者的PFS及OS。化疗+免疫±贝伐珠单抗的疗效可能是一种更有效的挽救性治疗方案。

Objective:To investigate the prognosis of patients with recurrent cervical cancer who received salvage therapy after immune checkpoint inhibitor treatment and to determine the optimal salvage therapy.Methods:Clinical and pathological datas were collected from 134 patients with cervical cancer who progressed after immune checkpoint inhibitor treatment at Hunan Cancer Hospital from February 1,2018,to December 31,2022.They were divided into the treatment group and the observation group.The treatment group,consisting of 65 patients,received different salvage therapy regimens:chemotherapy±bevacizumab(Chemo subgroup),chemotherapy±bevacizumab combined with immune checkpoint inhibitor(Chemo+ICIs subgroup),and immune checkpoint inhibitor combined with tyrosine kinase inhibitor(ICIs+TKIs subgroup).The observation group consisted of 69 patients who did not receive further anti-tumor treatment after immune progression.The progression-free survival-1(PFS-1),overall survival-1(OS-1),progression-free survival-2(PFS-2),and overall survival-2(OS-2)of both groups were observed,as well as the PFS-2 and OS-2 of different salvage treatment regimens.Results:The median PFS-1 was 4.9 months in both the treatment group and the control group,and the difference was not statistically significant(P=0.904).In the treatment group and control group,28 and 52 patients died,respectively.The median OS-1 was 22.7 months in the treatment group and 10.9 months in the control group,and the difference was statistically significant(P=0.000).The median PFS-2 and OS-2 in the treatment group were 5.7 months and 14 months,respectively.The PFS-2 for the different salvage therapy regimens,including Chemo subgroup,Chemo+ICIs subgroup,and ICIs+TKIs subgroup,were 4.5,7.0,and 5.1 months,respectively,there were no statistically significant differences among them.The median OS-2 for the different salvage therapy regimens were 14.7,19,and 6.9 months,respectively.The comparison between the Chemo+ICIs subgroup and the ICIs+TKIs subgroup showed a statistically significant difference in median OS-2(P=0.029).However,the incidence of adverse reactions with combination chemotherapy was higher,there were no statistically significant differences.Conclusion:These findings suggest that salvage therapy should be considered for patients with recurrent cervical cancer after immune checkpoint inhibitor treatment,and the optimal salvage therapy should be chosen based on individual patient characteristics.It appears that chemotherapy combined with immune checkpoint inhibitor±bevacizumab may be a more effective salvage therapy regimen.