曲妥珠单抗辅助皮下注射用于 HER2 阳性早期乳腺癌：SafeHer III 期研究中按体重分组的安全性和活动性医疗状况亚组分析。
Adjuvant Subcutaneous Trastuzumab for HER2-Positive Early Breast Cancer: Subgroup Analyses of Safety and Active Medical Conditions by Body Weight in the SafeHer Phase III Study.
机构信息
Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
Kliniken Essen-Mitte, Essen, Germany.
出版信息
Oncologist. 2018 Oct;23(10):1137-1143. doi: 10.1634/theoncologist.2018-0065. Epub 2018 Jul 17.
BACKGROUND
This SafeHer subgroup analysis assessed the safety of fixed-dose subcutaneous trastuzumab (H SC) as an adjuvant therapy in HER2-positive early breast cancer (EBC) by body weight.
PATIENTS AND METHODS
Patients with HER2-positive EBC not previously treated with anti-HER2 therapy received H SC 600 mg (every 3 weeks for 18 cycles), with neoadjuvant or adjuvant chemotherapy or without adjuvant chemotherapy. Adverse events (AEs) were assessed throughout treatment and at final follow-up (28 ±5 days after last treatment). Subgroups were categorized by body weight, Asian origin, and chemotherapy administration. All analyses were descriptive.
RESULTS
Of 2,577 patients enrolled, 2,573 received ≥1 dose of study medication and were included in this safety analysis. Median body weight at baseline was 67.0 kg (range 33.6-150.0 kg). Any-grade AEs occurred in 88.7% (2,282/2,573) of the overall population, versus 87.1% (590/677) of the lowest bodyweight quartile (≤59 kg), 90.0% (561/623) of the highest quartile (>77 kg), and 86.5% (327/378) of the Asian population. Grade ≥3 AEs occurred in 23.2% (596/2,573) of the overall population, 17.9% (121/677) of the lowest bodyweight quartile, 26.8% (167/623) of the highest quartile, and 15.3% (58/378) of the Asian population. The highest bodyweight quartile had the highest incidence of medical conditions at baseline (highest quartile, 75.6%; lowest quartile, 56.1%).
CONCLUSION
These data support the use of fixed-dose H SC as an adjuvant therapy in HER2-positive EBC and confirm the comparable safety profile of H SC in patients with low body weight or of Asian origin versus the overall population in SafeHer. ClinicalTrials.gov: NCT01566721.
IMPLICATIONS FOR PRACTICE
The safety profile of fixed-dose subcutaneous trastuzumab (H SC) was comparable between patients in the lowest bodyweight subgroup and the overall patient population, and also between patients of Asian origin (of whom a higher proportion often fall within the lower bodyweight quartiles) and the overall population. The safety data from this SafeHer subgroup analysis therefore support the use of fixed-dose H SC 600 mg administered every 3 weeks as an adjuvant therapy for patients with HER2-positive early breast cancer across different bodyweight subgroups and in the Asian patient population.
背景
本 SafeHer 亚组分析按体重评估了固定剂量皮下曲妥珠单抗（H SC）作为辅助治疗 HER2 阳性早期乳腺癌（EBC）的安全性。
患者和方法
既往未接受过抗 HER2 治疗的 HER2 阳性 EBC 患者接受 H SC 600 mg（每 3 周 18 个周期），联合新辅助或辅助化疗或不联合辅助化疗。整个治疗期间和最后一次随访（最后一次治疗后 28 ±5 天）时评估不良事件（AE）。亚组按体重、亚洲血统和化疗管理进行分类。所有分析均为描述性的。
结果
在 2577 名入组患者中，2573 名患者接受了至少 1 剂研究药物，并纳入本安全性分析。基线时的中位体重为 67.0 kg（范围 33.6-150.0 kg）。总体人群中任何级别 AE 发生率为 88.7%（2282/2573），最低体重四分位组（≤59 kg）为 87.1%（590/677），最高四分位组（>77 kg）为 90.0%（561/623），亚洲人群为 86.5%（327/378）。总体人群中≥3 级 AE 发生率为 23.2%（596/2573），最低体重四分位组为 17.9%（121/677），最高四分位组为 26.8%（167/623），亚洲人群为 15.3%（58/378）。最高体重四分位数组的基线合并症发生率最高（最高四分位数组为 75.6%；最低四分位数组为 56.1%）。
结论
这些数据支持固定剂量 H SC 作为 HER2 阳性 EBC 的辅助治疗，并证实 H SC 在体重较轻或亚洲血统的患者中的安全性与总体人群相当。ClinicalTrials.gov：NCT01566721。
临床意义
固定剂量皮下曲妥珠单抗（H SC）的安全性在最低体重亚组患者和总体患者人群之间、在亚洲裔患者（其中更高比例的患者通常属于较低体重四分位数）和总体患者人群之间具有可比性。因此，本 SafeHer 亚组分析的安全性数据支持每 3 周使用固定剂量 H SC 600 mg 作为辅助治疗用于不同体重亚组和亚洲患者人群的 HER2 阳性早期乳腺癌患者。
Zotero 插件