吉西他滨长疗程维持化疗有助于中国晚期乳腺癌患者生存获益的多中心真实世界研究

Gemcitabine long-term maintenance chemotherapy benefits patients with survival:a multicenter,real-world study of advanced breast cancer treatment in China

目的探讨吉西他滨为主的维持治疗对晚期乳腺癌治疗疗效的影响及影响治疗持续时间的主要原因。方法研究为前瞻性多中心研究,2017年1月至2019年1月期间从10家医疗中心选取接受含吉西他滨单药或联合其他化疗或靶向治疗的晚期乳腺癌患者,收集吉西他滨为主方案的治疗线数、剂量、周期数、不良反应、停药原因以及疗效等数据,生存分析采用Kaplan-Meier方法,预后影响因素的单因素分析采用log rank检验,多因素分析采用Cox回归模型。结果研究共筛选全国10家医院共239例晚期乳腺癌患者,最终纳入224例患者进行分析。全组患者中位年龄52岁(26~77岁),其中Luminal型83例,三阴性97例,人表皮生长因子受体2阳性型44例。55.4%(124/224)为绝经后患者。完全缓解(CR)5例,部分缓解(PR)77例,疾病稳定(SD)112例,疾病进展(PD)27例。客观有效率为36.6%(82/224)。Ⅲ级及以上不良反应主要包括白细胞下降(9例)、中性粒细胞下降(49例)、血小板下降(15例)、转氨酶升高(2例)。中位随访时间41个月(26~61个月),中位无进展生存时间(PFS)为5.6个月。引起治疗结束的主要原因包括疾病进展90例、患者个人原因终止治疗51例、严重不良反应不耐受18例、医师评估后治疗结束65例。治疗周期>6个周期较≤6个周期患者在PFS有明显的延长(8.2和5.4个月,HR=2.474,95%CI:1.730~3.538,P<0.001)。结论吉西他滨为主的治疗方案在中国人群中有较好的疗效和耐受性,长程维持治疗有利于改善生存。

Objective This study collected a real-world data on survival and efficacy of gemcitabine-containing therapy in advanced breast cancer.Aimed to find the main reasons of affecting the duration of gemcitabine-base therapy in advanced breast cancer patients.Methods Advanced breast cancer patients who received gemcitabine-base therapy from January 2017 to January 2019 were enrolled(10 hospitals).The clinicopathological data,the number of chemotherapy cycles and the reasons for treatment termination were collected and analyzed.To identify the reasons related with continuous treatment for advanced breast cancer and the factors which affect the survival and efficacy.Results A total of 224 patients with advanced breast cancer were enrolled in this study,with a median age of 52 years(26-77 years),55.4%(124/224)was postmenopausal.Luminal type were 83 cases,TNBC were 97 cases,and human epidermal growth factor receptor 2(HER's-2)overexpression were 44.At the analysis,224 patients who received the gemcitabine-based regimens were evaluated,included 5 complete reponse(CR),77 partial response(PR),112 stable disease(SD)and 27 progressive disease(PD).The objective response rate(ORR)was 36.6%(82/224).Seventy patients had serious adverse diseases,including leukopenia(9),neutrophilia(49),thrombocytopenia(15),and elevated transaminase(2).The median follow-up time was 41 months(26~61 months),and the median PFS was 5.6 months.The reasons of termination treatment were listed:disease progression were 90 patients;personal reasons were 51 patients;adverse drug reactions were 18 patients;completed treatment were 65 patients.It was found that progression-free survival(PFS)was significantly longer in patients receiving>6 cycles than that in patients with≤6 cycles(8.2 months vs 5.4 months,HR=2.474,95%CI:1.730-3.538,P<0.001).Conclusions Gemcitabine-based regimen is generally well tolerated in the Chinese population and has relatively ideal clinical efficacy in the real world.The median PFS is significantly prolonged when the number of treatment cycles are appropriately increased.