阿比特龙序贯恩扎卢胺治疗转移性去势抵抗性前列腺癌临床分析

Clinical analysis of sequential treatment using abiraterone and enzalutamide for metastatic castration-resistant prostate cancer

目的:阿比特龙序贯恩扎卢胺治疗是转移性去势抵抗性前列腺癌(metastatic castration-resistant prostate cancer, mCRPC)患者可选择的治疗方式之一,可使部分患者获益。然而,尚缺乏这种序贯治疗方案在中国mCRPC人群真实世界的数据。方法:回顾性分析2018年1月—2023年4月于中山大学肿瘤防治中心采用阿比特龙序贯恩扎卢胺治疗的136例mCRPC患者的临床资料。根据转移性激素敏感性前列腺癌(metastatic hormone-sensitive prostate cancer, mHSPC)阶段治疗方案分为联合治疗组和阶梯治疗组。其中联合治疗组57例,患者在mHSPC阶段使用雄激素剥夺治疗(androgen deprivation therapy, ADT)联合阿比特龙+泼尼松治疗;阶梯治疗组79例,患者在mHSPC阶段仅使用ADT治疗,进展为mCRPC再联合阿比特龙+泼尼松治疗。主要研究终点是恩扎卢胺治疗PSA最大下降比例超过50%(PSA50)的情况。结果:恩扎卢胺平均使用时间为(4.5±2.2)个月,18.38%的患者达到PSA50。多因素分析显示mHSPC阶段治疗方案(联合治疗组vs阶梯治疗组)(OR=4.52,95%CI:1.27~16.14,P=0.02)、阿比特龙有效时间(OR=1.11,95%CI:1.03~1.19,P=0.005)和阿比特龙治疗进展后到序贯恩扎卢胺的间隔时间(OR=0.83,95%CI:0.72~0.95,P=0.007)是PSA50的独立预测因素。采用倾向性评分根据临床基线特征对联合治疗组和阶梯治疗组间的患者进行1∶1匹配,结果显示联合治疗组相对于阶梯治疗组患者有着更高的PSA50(31.58%vs 7.02%)。结论:阿比特龙序贯恩扎卢胺可使部分mCRPC患者获得PSA反应。阿比特龙有效时间长,在mHSPC期使用ADT联合阿比特龙治疗,以及阿比特龙耐药后序贯恩扎卢胺时间间隔短的患者更可能在序贯治疗中出现PSA50。

Objective To analyze the real-world data on the sequential treatment regimen of abiraterone acetate followed by enzalutamide in Chinese patients with metastatic castration-resistant prostate cancer(mCRPC).Methods The retrospective analysis included 136 mCRPC patients treated with abiraterone acetate followed by enzalutamide from January 2018 to April 2023.The patients were divided into two groups based on the treatment strategy in the metastatic hormone-sensitive prostate cancer(mHSPC)stage:the"combination therapy"group and the"step-wise therapy"group.In the combined therapy group,57 patients received androgen deprivation therapy(ADT)combined with abiraterone and prednisone during the mHSPC stage.In the step-wise therapy group,79 patients were initially treated with ADT during the mHSPC stage,and subsequently progressed to mCRPC before receiving combined treatment with abiraterone plus prednisone.The primary endpoint was the proportion of patients with a PSA maximum decline of over 50%(PSA50)following enzalutamide treatment.Results The mean duration of enzalutamide use was(4.5±2.2)months,and 18.38%of patients achieved a PSA50 response.Multifactorial analysis revealed that the treatment strategy at the mHSPC stage(combined treatment vs.step-wise treatment)(OR=4.52,95%CI:1.27-16.14,P=0.02),the effective duration of abiraterone(OR=1.11,95%CI:1.03-1.19,P=0.005),and the time interval from frontline abiraterone treatment progression to sequential enzalutamide(OR=0.83,95%CI:0.72-0.95,P=0.007)were independent predictive factors for PSA50.By using propensity score matching based on clinical baseline characteristics,patients in the combination therapy group and the step-wise therapy group were matched at a 1∶1 ratio.The results demonstrated that patients in the combination therapy group had a higher PSA50 response compared to those in the step-wise therapy group(31.58%vs 7.02%).Conclusion Sequential treatment using abiraterone acetate and enzalutamide can lead to PSA response in some mCRPC patients.Those with longer frontline abiraterone effective duration,a shorter time interval from frontline abiraterone treatment progression to sequential enzalutamide,and the use of ADT combined with abiraterone therapy strategy during the mHSPC period are more likely to experience PSA50 during sequential therapy.