奥拉帕利联合贝伐珠单抗治疗铂敏感复发性卵巢癌患者疗效及对血清HE4、CA125和CTC水平的影响

Therapeutic effect of olaparib combined with bevacizumab for patients with platinum-sensitive recurrent ovarian cancer and its influences on serum HE4, CA125 and CTC levels

摘要

目的 探究奥拉帕利(OLA)联合贝伐珠单抗(BEV)治疗复发性铂类敏感性(PSR)卵巢癌患者疗效及对血清人附睾蛋白4(HE4)、糖类抗原125(CA125)和循环肿瘤细胞(CTC)水平的影响。方法 回顾性分析2016年2月至2021年4月于本院就诊并接受治疗的108例PSR卵巢癌患者资料,按照治疗方案的不同分组,给予多柔比星脂质体联合卡铂化疗纳入常规组,OLA及BEV联合多柔比星脂质体加卡铂治疗纳入试验组,应用倾向性评分匹配法(1:1匹配,卡钳值设置为0.01),最终两组各纳入46例患者。比较两组患者实体瘤疗效、治疗前后血清肿瘤标志物(HE4、CA125、CTC)水平、T淋巴细胞(CD4⁺、CD8⁺、CD3⁺、CD4⁺/CD8⁺)水平及药物毒副反应、随访3年疾病进展情况(无进展生存期、总生存期)。采用Kaplan-Meier法绘制生存曲线。结果 试验组患者总有效率(ORR)、病灶控制率(DCR)分别为56.52%、84.78%,均高于常规组的34.78%、60.87%,差异均有统计学意义(t=4.381、6.646,P<0.05);治疗后试验组HE4、CA125、CTC水平低于常规组(t=3.903、7.588、8.312,P<0.05);治疗后组间CD4⁺、CD8⁺、CD3⁺、CD4⁺/CD8⁺水平比较无显著差异(t=1.109、0.754、0.473、0.611,P>0.05);两组胃肠道反应、中性粒细胞减少Ⅲ~Ⅳ级不良反应发生率比较无显著差异(χ²=3.101、2.044,P>0.05),试验组中性粒细胞减少Ⅰ~Ⅱ级发生率低于常规组(χ²=5.361,P<0.05);随访3年,试验组无进展生存期为(14.90±1.76)月,总生存期为(25.52±1.64)月,常规组无进展生存期为(8.78±1.16)月,总生存期为(19.06±1.59)月,试验组无进展生存期、总生存期均高于常规组(χ²=10.267,P<0.001,χ²=7.681,P=0.006)。结论 奥拉帕利联合贝伐珠单抗在常规铂类化疗基础上治疗PSR卵巢癌疗效确切,可降低肿瘤标志物水平,抑制肿瘤细胞的生长和转移,毒副反应较小,远期生存预后较好。

Abstract

Objective To explore therapeutic effect of olaparib (OLA) combined with bevacizumab (BEV) for patients with platinum-sensitive recurrent (PSR) ovarian cancer and its influences on serum levels of human epididymis protein 4 (HE4), carbohydrate antigen 125 (CA125) and circulating tumor cells (CTC). Methods The clinical data of 108 patients with PSR ovarian cancer who were treated in The First Hospital of Jiaxing City over a period from February 2016 to April 2021 were retrospectively analyzed. According to difference in treatment regimen, the patients who received doxorubicin liposome combined with carboplatin chemotherapy were included in conventional treatment group, and the patients who received OLA combined with BEV therapy on the basis of doxorubicin liposome combined with carboplatin chemotherapy were enrolled as experimental treatment group. The propensity score matching method (caliper=0.01, 1:1 matching) was used, and 46 patients with comparable baseline data were finally included in each group. The efficacy for solid tumor, serum levels of tumor markers (HE4, CA125, CTC) and T lymphocytes (CD4⁺, CD8⁺, CD3⁺, CD4⁺/CD8⁺) before and after treatment, drugs' toxic and side effects, and disease progression status (progression-free survival time, overall survival time) at 3 years of follow-up were compared between the two groups. Kaplan-Meier method was used to draw survival curves. Results Objective response rate (ORR) and disease control rate (DCR) in the experimental treatment group were 56.52% and 84.78% respectively, which were higher than 34.78% and 60.87% in the conventional treatment group, and there were significant differences between the two groups (t=4.381 and 6.646 respectively, both P<0.05). After treatment, the serum levels of HE4, CA125 and CTC in the experimental treatment group were significantly lower than those in the conventional treatment group (t=3.903, 7.588 and 8.312 respectively, all P<0.05). There were no significant differences in serum levels of CD4⁺, CD8⁺, CD3⁺ and CD4⁺/CD8⁺ ratio between the two groups after treatment (t=1.109, 0.754, 0.473 and 0.611 respectively, all P>0.05), and also, there were no significant differences in incidence rates of grades Ⅲ and Ⅳ of gastrointestinal reaction and neutropenia between the two groups (χ²=3.101 and 2.044 respectively, both P>0.05). The incidence rate of grades Ⅰ and Ⅱ of neutropenia in the experimental treatment group was lower than that in the conventional treatment group (χ²=5.361, P<0.05). Within the 3-year follow-up, the progression-free survival time and overall survival time in the experimental treatment group were 14.90±1.76 months and 25.52±1.64 months and those in the conventional treatment group were 8.78±1.16 months and 19.06±1.59 months, indicating that the progression-free survival time and the overall survival time in the experimental treatment group were longer than those in the conventional treatment group (χ²=10.267, P<0.001, χ²=7.681, P=0.006). Conclusion Olaparib combined with bevacizumab on the basis of doxorubicin liposome combined with carboplatin chemotherapy has exact efficacy in treatment of PSR ovarian cancer, and it can reduce serum levels of tumor markers, and inhibit growth and metastasis of the tumor cells, with small toxic and side effects and good long-term survival prognosis.

关键词

复发性卵巢癌 / 铂类敏感 / 奥拉帕利 / 贝伐珠单抗 / 疗效 / 肿瘤标志物 / 生存期

Key words

recurrent ovarian cancer / platinum-sensitive / olaparib / bevacizumab / therapeutic effect / tumor marker / survival time

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基金资助

嘉兴市科技计划项目(2024AD10007)