曲妥珠单抗联合或不联合化疗治疗人表皮生长因子受体 2 阳性老年早期乳腺癌的随机对照试验。

Randomized Controlled Trial of Trastuzumab With or Without Chemotherapy for HER2-Positive Early Breast Cancer in Older Patients.

机构信息

Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.

Department of Breast and Endocrine Surgery, Okayama University Hospital, Okayama, Japan.

出版信息

J Clin Oncol. 2020 Nov 10;38(32):3743-3752. doi: 10.1200/JCO.20.00184. Epub 2020 Sep 16.

DOI:10.1200/JCO.20.00184

PMID:32936713

Abstract

PURPOSE

Adjuvant trastuzumab monotherapy has not been compared with trastuzumab + chemotherapy. We investigated the relative value of trastuzumab monotherapy for older patients with breast cancer.

METHODS

This study was an open-label, randomized controlled study with a treatment selection design in which a noninferiority criterion was predefined. Patients aged 70-80 years with surgically treated human epidermal growth factor receptor 2-positive invasive breast cancer received trastuzumab monotherapy or trastuzumab + chemotherapy. The primary end point was disease-free survival (DFS) with assessment of prespecified hazard ratio (HR), relapse-free survival (RFS), adverse events (AEs), health-related quality of life (HRQoL), and restricted mean survival time (RMST).

RESULTS

The study involved 275 patients (mean age, 73.5 years) who were followed up for a mean of 4.1 years (range, 0.3-8.0 years). The percentages of patients by cancer stage were as follows: I (pT > 0.5 cm), 43.6%; IIA, 41.7%; IIB, 13.5%; and IIIA, 1.1%. Three-year DFS was 89.5% with trastuzumab monotherapy versus 93.8% with trastuzumab + chemotherapy (HR, 1.36; 95% CI, 0.72 to 2.58; = .51). At 3 years, RMST differed by -0.39 months between arms (95% CI, -1.71 to 0.93; = .56). Three-year RFS was 92.4% with trastuzumab monotherapy versus 95.3% with trastuzumab + chemotherapy (HR, 1.33; 95% CI, 0.63 to 2.79; = .53). Common AEs were anorexia (7.4% 44.3%; < .0001) and alopecia (2.2% 71.7%; < .0001), and grade 3/4 nonhematologic AEs occurred in 11.9% versus 29.8% ( = .0003) for trastuzumab monotherapy versus trastuzumab + chemotherapy, respectively. Clinically meaningful HRQoL deterioration rate showed significant differences at 2 months (31% for trastuzumab monotherapy 48% for trastuzumab + chemotherapy; = .016) and at 1 year (19% 38%; = .009).

CONCLUSION

The primary objective of noninferiority for trastuzumab monotherapy was not met. However, the observed loss of survival without chemotherapy was < 1 month at 3 years. Therefore, and in light of the lower toxicity and more favorable HRQoL profile, trastuzumab monotherapy can be considered an adjuvant therapy option for selected older patients.

摘要

目的

曲妥珠单抗辅助单药治疗尚未与曲妥珠单抗联合化疗进行比较。我们研究了曲妥珠单抗单药治疗老年乳腺癌患者的相对价值。

方法

这是一项开放标签、随机对照研究，采用治疗选择设计，预设了非劣效性标准。接受手术治疗的人表皮生长因子受体 2 阳性浸润性乳腺癌且年龄为 70-80 岁的患者接受曲妥珠单抗单药治疗或曲妥珠单抗联合化疗。主要终点是无病生存（DFS），评估预设的危险比（HR）、无复发生存（RFS）、不良事件（AEs）、健康相关生活质量（HRQoL）和受限平均生存时间（RMST）。

结果

该研究纳入了 275 例（平均年龄 73.5 岁）患者，平均随访时间为 4.1 年（范围为 0.3-8.0 年）。各期癌症患者比例如下：I 期（pT > 0.5 cm）占 43.6%；IIA 期占 41.7%；IIB 期占 13.5%；IIIA 期占 1.1%。曲妥珠单抗单药治疗组 3 年 DFS 为 89.5%，曲妥珠单抗联合化疗组为 93.8%（HR，1.36；95%CI，0.72 至 2.58； =.51）。3 年时，RMST 臂间差异为-0.39 个月（95%CI，-1.71 至 0.93； =.56）。曲妥珠单抗单药治疗组 3 年 RFS 为 92.4%，曲妥珠单抗联合化疗组为 95.3%（HR，1.33；95%CI，0.63 至 2.79； =.53）。常见的 AEs 是厌食症（7.4% 44.3%；<.0001）和脱发（2.2% 71.7%；<.0001），曲妥珠单抗单药治疗组和曲妥珠单抗联合化疗组分别有 11.9%和 29.8%发生 3/4 级非血液学 AEs（ =.0003）。2 个月时（曲妥珠单抗单药治疗组为 31%，曲妥珠单抗联合化疗组为 48%； =.016）和 1 年时（曲妥珠单抗单药治疗组为 19%，曲妥珠单抗联合化疗组为 38%； =.009），HRQoL 恶化率出现有统计学意义的差异。