紫杉醇+卡铂密集化疗联合曲妥珠单抗新辅助治疗对比标准辅助治疗对人表皮生长因子受体2阳性且激素受体阴性乳腺癌患者生存影响的前瞻性研究

Dose-dense paclitaxel plus carboplatin in combination with trastuzumab neoadjuvant versus standard adjuvant therapy in human epidermal growth factor receptor-2 positive and hormone receptor negative breast cancer:a prospective cohort study

目的评价紫杉醇+卡铂密集化疗联合曲妥珠单抗新辅助治疗Ⅱ~Ⅲ期人表皮生长因子受体2(HER-2)阳性且激素受体(HR)阴性乳腺癌的远期疗效和安全性。方法纳入2013年7月至2019年11月中国医学科学院肿瘤医院肿瘤内科收治的Ⅱ~Ⅲ期HER-2阳性且HR阴性乳腺癌,未手术者予剂量密集PCbH方案(紫杉醇+卡铂剂量密集化疗联合曲妥珠单抗)新辅助治疗,后行根治性手术切除,已手术者予标准辅助治疗[AC-TH方案(表柔比星或吡柔比星+环磷酰胺序贯多西他赛+曲妥珠单抗)或TCbH方案(多西他赛+卡铂联合曲妥珠单抗)],通过倾向性评分匹配新辅助、辅助治疗两组患者进行生存分析,评估不良反应。结果共入选符合条件的患者166例,其中新辅助治疗组51例,辅助治疗组115例。与辅助治疗组相比,新辅助治疗组患者更年轻(<35岁者分别占19.6%和5.2%,P=0.014)、肿瘤更大(T3期患者分别占62.7%和7.8%,P<0.001)、分期更晚(ⅡA期者分别占2.0%和41.7%,P<0.001)。49对患者倾向性评分匹配成功,匹配后的新辅助治疗组和辅助治疗组协变量均衡性良好。匹配人群的中位随访时间为46.5个月。新辅助治疗组和辅助治疗组患者的4年无复发生存率分别为73.3%(95%CI:59.0%~87.6%)和80.6%(95%CI:67.9%~93.3%),4年总生存率分别为91.5%(95%CI:81.7%~100.0%)和97.8%(95%CI:93.5%~100.0%),差异均无统计学意义(P值分别为0.418和0.314)。新辅助治疗组3~4级中性粒细胞减少的发生率为45.1%(23/51),低于辅助治疗组的53.9%(62/115),且心脏安全性更好。结论Ⅱ~Ⅲ期HER-2阳性且HR阴性乳腺癌,可选择去蒽环方案新辅助化疗联合抗HER-2靶向治疗,同时应积极探索兼顾疗效与安全的优化药物组合。

Objective To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stagesⅡ-Ⅲhuman epidermal growth factor receptor-2(HER-2)positive and hormone receptor(HR)negative breast cancer.Methods The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital,Chinese Academy of Medical Sciences.Patients with HER-2 positive and HR negative breast cancer in stagesⅡ-Ⅲwere enrolled to receive neoadjuvant therapy(NAT)of dose-dense paclitaxel(175 mg/m^(2))plus carboplatin(AUC=4.0)biweekly for 6 cycles in combination with trastuzumab(PCbH),and matched patients who received standard adjuvant therapy of physicians′choice were recruited for survival and safety comparison.Results From July 2013 to November 2019,166 patients were included(neoadjuvant 51,adjuvant 115).Compared with those who received adjuvant therapy,patients receiving NAT were younger(<35 years:19.6%vs 5.2%,P=0.014),had larger tumors(T3:62.7%vs 7.8%,P<0.001)and more advanced diseases(stageⅡA:2.0%vs 41.7%,P<0.001).Patients in the neoadjuvant group all received surgery,and 96(83.5%)in the adjuvant group received anthracycline-and-taxane-containing regimens.A total of 98 patients(49 pairs)were matched,and the covariates between the two groups were acceptably balanced.Within a median follow-up of 46.5(range,14-87)months,the 4-year recurrence-free survival(RFS)rate among patients who received NAT was 73.3%(95%CI:59.0%-87.6%),versus 80.6%(95%CI:67.9%-93.3%)among those in the adjuvant group without statistical difference(P=0.418).A similar result was observed for the 4-year overall survival(OS)[neoadjuvant versus adjuvant:91.5%(95%CI:81.7%-100.0%)vs 97.8%(95%CI:93.5%-100.0%),P=0.314].Compared with standard adjuvant therapy,PCbH was related to less neutropenia and better cardiac safety.Conclusions These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stagesⅡ-ⅢHER-2-positive and HR-negative breast cancer.Optimized regimens with both efficacy and safety are needed and to be further investigated.