德曲妥珠单抗治疗HER2过表达和低表达转移性乳腺癌的效果及预后影响因素分析

Efficacy of trastuzumab deruxtecan in treatment of metastatic breast cancer with overexpression or low expression of HER2 and the influencing factors of prognosis

目的探讨德曲妥珠单抗(T-DXd)治疗人表皮生长因子受体2(HER2)不同表达水平的转移性乳腺癌(MBC)患者的效果及预后影响因素。方法回顾性病例系列分析和队列研究。回顾性收集2021年8月至2023年8月在西安国际医学中心医院接受T-DXd治疗的20例HER2不同表达水平MBC患者临床资料,分析T-DXd的疗效及安全性。采用Cox比例风险模型对预后影响因素进行多因素分析。结果20例患者均为女性,中位年龄[M(Q1,Q3)]49岁(40岁,58岁)。20例中,12例HER2低表达[免疫组织化学HER2+,或免疫组织化学++且荧光原位杂交(FISH)阴性],8例HER2过表达(免疫组织化学HER2+++,或免疫组织化学++且FISH阳性);T-DXd中位治疗线数为6线(3线,7线);14例患者部分缓解,3例患者疾病稳定,3例患者疾病进展,客观缓解率(ORR)为70%(14/20),疾病控制率为85%(17/20)。8例HER2过表达患者中客观缓解6例,12例HER2低表达患者中客观缓解8例,两组间ORR差异无统计学意义(P=1.000)。患者主要不良反应为恶心(14例)、呕吐(12例)、白细胞减少(10例)、天冬氨酸氨基转移酶升高(10例)、丙氨酸氨基转移酶升高(9例)、贫血(8例)、疲乏(8例)、脱发(8例)、中性粒细胞减少(6例)及血小板减少(5例);≥3级不良反应主要为骨髓抑制及消化道反应,发生率均≤10%。中位随访7.1个月(1.9个月,11.5个月),患者中位无进展生存(PFS)时间为6.5个月(95%CI:3.9~9.1个月)。HER2过表达患者中位PFS时间长于HER2低表达患者[7.0个月(95%CI:6.4~7.6个月)比4.0个月(95%CI:1.7~6.3个月)],两组PFS差异有统计学意义(P=0.025)。多因素Cox回归分析显示,HER2过表达是接受T-DXd治疗MBC患者PFS的独立保护因素(HR=0.265,95%CI:0.075~0.945,P=0.041)。结论HER2过表达或低表达的MBC患者接受T-DXd治疗有较好的疗效和安全性。HER2过表达可能预示接受T-DXd治疗的MBC患者有较好的PFS,可能成为预测此类患者PFS的生物标志物,但可能不影响ORR。

Objective To investigate the effect of trastuzumab deruxtecan(T-DXd)in the treatment of metastatic breast cancer(MBC)patients with different expression levels of human epidermal growth factor receptor 2(HER2)and the influencing factors of prognosis.Methods The retrospective case series analysis and cohort study were conducted.Clinical data of 20 MBC patients with different expression levels of HER2 treated with T-DXd at Xi'an International Medical Center Hospital from August 2021 to August 2023 were retrospectively collected to analyze the efficacy and safety of T-DXd.The Cox proportional hazards model was used for multivariate analysis of prognostic factors.Results All 20 patients were female,with a median age[M(Q1,Q3)]of 49 years old(40 years old,58 years old).Of the 20 cases,12 had low expression of HER2[immunohistochemistry HER2+,or immunohistochemistry++and fluorescence in situ hybridization(FISH)-negative],and 8 had overexpression of HER2(immunohistochemistry HER2+++,or immunohistochemistry++and FISH-positive);median number of lines of treatment with T-DXd was 6 lines(3 lines,7 lines);14 patients had partial remission,3 patients had stable disease,and 3 patients had disease progression,with an objective remission rate(ORR)of 70%(14/20)and a disease control rate of 85%(17/20).Eight patients with overexpression of HER2 had objective remission in 6 cases,and 12 patients with low expression of HER2 had objective remission in 8 cases,and the ORR difference between the two groups was not statistically significant(P=1.000).The main adverse reactions of the patients were nausea(14 cases),vomiting(12 cases),leukopenia(10 cases),elevated aspartate aminotransferase(10 cases),elevated alanine aminotransferase(9 cases),anemia(8 cases),fatigue(8 cases),alopecia(8 cases),neutropenia(6 cases),and thrombocytopenia(5 cases);≥grade 3 adverse reactions were bone marrow suppression and gastrointestinal reactions,all with an incidence of≤10%.The median follow-up time was 7.1 months(1.9 months,11.5 months).The median progression-free survival(PFS)time was 6.5 months(95%CI:3.9-9.1 months),and the median PFS time of patients with overexpression of HER2 was longer than that of patients with low expression of HER2[7.0 months(95%CI:6.4-7.6 months)vs.4.0 months(95%CI:1.7-6.3 months)],and the difference in PFS between the two groups was statistically significant(P=0.025).Multivariate Cox regression analysis showed that overexpression of HER2 was an independent protective factor for PFS in MBC patients treated with T-DXd(HR=0.265,95%CI:0.075-0.945,P=0.041).Conclusions MBC patients with overexpression or low expression of HER2 have a good therapeutic effect and safety profile when treated with T-DXd.The overexpression of HER2 may predict good PFS in MBC patients treated with T-DXd,and may serve as a biomarker for predicting PFS in such patients,but it may not affect the ORR.