Purpose

Standard-of-care for HER2-positive metastatic breast cancer (HER2 + mBC) patients consists of trastuzumab ± pertuzumab with chemotherapy in first-line (1L), and ado-trastuzumab emtansine (T-DM1) or the more recently approved trastuzumab deruxtecan (T-DXd) in second-line (2L). Contemporary data on treatment sequencing and real-world effectiveness is limited. This study aims to report 2L treatments and outcomes among HER2 + mBC patients in the United States (US).

Methods

HER2 + mBC patients initiating 2L treatment (index date) between January 2014 and February 2021 were identified from the Syapse Learning Health Network (LHN) database. Summary statistics for patient characteristics, treatment received, reasons for 2L discontinuation and time to 2L-clinical outcomes are reported.

Results

Of the 312 patients initiating 2L treatment, had a median age of 59 years (interquartile range [IQR], 50–66) at the start of 2L. The majority were white (69%) and had de novo mBC (62%). Top three 2L regimens included T-DM1 ± endocrine therapy (29%), trastuzumab/pertuzumab/taxane (10%) and T-DM1/trastuzumab (8%). Around 88% discontinued 2L and 63% received subsequent treatment. Median time-to-next-treatment was 10.6 months (95% CI, 8.8–13.3) and real-world progression-free-survival was 7.9 months (95% CI, 7.0–9.9). Among 274 patients who discontinued 2L, 47% discontinued due to progression and 17% because of intolerance/toxicity, respectively.

Conclusion

This real-world US study showed that approximately two-thirds of 2L patients received subsequent therapy and disease progression was the most common reason for 2L discontinuation highlighting the need for timely 2L treatment with the most efficacious drug to allow patients to achieve longer treatment duration and delayed progression.

中文翻译：

---

美国社区实践中 HER2 阳性转移性乳腺癌患者的治疗顺序和二线临床结果的真实世界研究

目的

HER2 阳性转移性乳腺癌 (HER2 + mBC) 患者的标准护理包括一线化疗的曲妥珠单抗 ± 帕妥珠单抗 (1L) 和 ado-曲妥珠单抗 emtansine (T-DM1) 或最近批准的曲妥珠单抗 deruxtecan (T-DXd) 在二线 (2L)。关于治疗测序和现实世界有效性的当代数据有限。本研究旨在报告美国 (US) HER2 + mBC 患者的 2L 治疗和结果。

方法

从 Syapse 学习健康网络 (LHN) 数据库中识别出 2014 年 1 月至 2021 年 2 月期间开始 2L 治疗（索引日期）的 HER2 + mBC 患者。报告了患者特征、接受的治疗、2L 停用原因以及 2L 临床结果时间的汇总统计数据。

结果

在开始 2L 治疗的 312 名患者中，2L 开始时的中位年龄为 59 岁（四分位数范围 [IQR]，50-66）。大多数是白人 (69%)，并且患有新发 mBC (62%)。排名前三位的 2L 治疗方案包括 T-DM1 ± 内分泌治疗 (29%)、曲妥珠单抗/帕妥珠单抗/紫杉烷 (10%) 和 T-DM1/曲妥珠单抗 (8%)。约 88% 停止 2L，63% 接受后续治疗。距下次治疗的中位时间为 10.6 个月（95% CI，8.8–13.3），实际无进展生存期为 7.9 个月（95% CI，7.0–9.9）。在 274 名停用 2L 的患者中，分别有 47% 的患者因病情进展而停药，17% 的患者因不耐受/毒性而停药。

结论

这项美国真实研究表明，大约三分之二的 2L 患者接受了后续治疗，而疾病进展是停止 2L 的最常见原因，这凸显了需要及时使用最有效的药物进行 2L 治疗，以使患者获得更长的治疗持续时间和进展延迟。