哌柏西利联合内分泌药物治疗中国晚期乳腺癌的不良反应真实世界研究

Adverse events of palbociclib combined with endocrine drugs in the treatment of advanced breast cancer in China:a real world study

目的探讨哌柏西利联合内分泌药物治疗激素受体(HR)阳性、人表皮生长因子受体2(HER2)阴性中国晚期乳腺癌的不良反应及可能相关的影响因素。方法回顾性分析解放军总医院第五医学中心乳腺肿瘤中心2016年1月至2020年9月接受哌柏西利治疗的患者的临床资料,计算各类不良事件发生率,并分析不良反应的影响因素。结果共纳入195例患者,中位年龄51岁(30~81岁),常见不良反应为白细胞减少(89.7%)、中性粒细胞减少(87.7%)、贫血(59.0%)、天冬氨酸转氨酶(AST)升高(35.9%)和乏力(31.8%),常见的3/4级不良反应为中性粒细胞减少(51.8%)、白细胞减少(37.9%)、血小板减少(6.2%)、贫血(4.6%)、AST升高(2.6%);33例(16.9%)剂量下调患者中,有30例(90.9%)因白细胞/中性粒细胞减少而减量;由于不良反应停药5例(2.6%),其中4例(2.1%)是由于白细胞/中性粒细胞减少;60岁及以上患者中,起始服用125 mg与低于125 mg患者的剂量下调率有显著差异(P<0.001);未发现与3/4级中性粒细胞减少有关的危险因素;发生3/4级中性粒细胞减少的患者中位PFS(10.0个月)明显长于未发生者(6.0个月)(P=0.029)。结论哌柏西利联合内分泌治疗在中国乳腺癌患者中最常见的不良反应为白细胞减少、中性粒细胞减少,白细胞/中性粒细胞减少是剂量下调的主要原因;临床实践中,≥60岁的患者可依据病情初始治疗即选择低剂量用药;未发现与3/4级中性粒细胞减少有关的危险因素,但发生3/4级中性粒细胞减少的患者可能有更长的PFS获益,还需进一步行前瞻性临床研究探索分析。

Objective To investigate the adverse events of palbociclib combined with endocrine drugs in the treatment of hormone receptor(HR)positive and human epidermal growth factor receptor 2(HER2)negative advanced breast cancer in China,and the possible influencing factors.Methods The clinical data of patients who received palbociclib treatment in breast cancer center of the Fifth Medical Center of PLA General Hospital between January 2016 and September 2020 were retrospectively analyzed,the incidence of adverse events was calculated and the influencing factors were analyzed.Results A total of 195 patients were included in the study,with a median age of 51 years(30~81 years).The common adverse events were leukopenia(89.7%),neutropenia(87.7%),anemia(59.0%),aspartate aminotransferase(AST)elevation(35.9%)and fatigue(31.8%).The common grade 3/4 adverse events were neutropenia(51.8%),leucopenia(37.9%),thrombocytopenia(6.2%),anemia(4.6%),and AST elevation(2.6%).Of the 33 patients(16.9%)with palbociclib dose down-regulation,30 patients(90.9%)had the dose reduced due to leukopenia/neutropenia.Five patients(2.6%)discontinued palbociclib due to adverse reactions,and 4(2.1%)of them were due to leukopenia/neutropenia.In patients of 60 years old or older,there was a significant difference in the rate of dose down-regulation between the group with the initial dose of 125 mg and those with the initial dose<125 mg(P<0.001).No risk factors were found related to grade 3/4 neutropenia.The median PFS of patients with grade 3/4 neutropenia was longer than that of patients without grade 3/4 neutropenia(10.0 months vs.6.0 months,P=0.029).Conclusion The most common adverse events of palbociclib combined with endocrine drugs in Chinese breast cancer patients are leukopenia and neutropenia.Leukopenia and neutropenia were the main reasons for palbociclib dose downregulation.Patients≥60 years old can choose low-dose medication.No risk factors related to grade 3/4 neutropenia were found.However,patients with grade 3/4 neutropenia may have longer PFS benefits.Further prospective clinical researches are needed.