Brezden-Masley Christine, Qadeer Rana, Senhaji Mouhri Zhor, Salvo Bianca, Bonar Nicolle, Spin Paul, Shokar Simran
University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada.
Medical Oncology, Mount Sinai Hospital, Toronto, Ontario, Canada.
BMJ Open. 2025 Sep 21;15(9):e100889. doi: 10.1136/bmjopen-2025-100889.
In current clinical practice, breast cancer is treated according to hormone receptor and human epidermal growth receptor 2 expression (HER2) status, which play an important role in disease management and overall prognosis. Trastuzumab deruxtecan (T-DXd) has been studied in multiple global prospective DESTINY-breast trials. Recent marketing authorisation for T-DXd has been granted from Health Canada for HER2-positive breast cancer who have received prior treatment with trastuzumab emtansine, or at least one prior anti-HER2-based regimen in the metastatic setting, or who have received a prior anti-HER2-based regimen in the neoadjuvant or adjuvant setting and developed disease recurrence during or within 6 months of completing neoadjuvant or adjuvant therapy. T-DXd is also indicated for HER2-low unresectable and/or metastatic breast cancer (mBC) patients who have received at least one prior line of chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy. However, there is a paucity of evidence assessing T-DXd in the real-world setting. As such, the overarching aim of this study is to generate Canadian real-world evidence on discontinuations and treatment modifications for patients with HER2+ and HER2-low mBC undergoing treatment with T-DXd.
This is a hybrid, longitudinal cohort study design leveraging patient support programme (PSP) secondary data with additional primary data collection to assess study treatment-related outcomes among patients with HER2+ and HER2-low mBC receiving treatment with T-DXd. Mainly, this study will leverage secondary data from the PSP, which will include clinical and demographic characteristics as well as duration, modification and intensity of treatment information for patients while enrolled in the PSP. These data will be supplemented with primary data, which will be collected via a patient questionnaire and include additional self-reported clinical and demographic characteristics not captured within the PSP, including follow-up data on therapies received, treatment discontinuation information after the PSP closure and frequency of CT scans and cardiac monitoring scans.
The study protocol was approved by the Advarra Institutional Review Board on 13 December 2023 (ID: D133HR00037). Findings will be disseminated by publication in peer-reviewed journals, through oral and poster presentations for various audiences, websites and scientific meetings. Written informed consent will be obtained from all patients prior to agreeing to participate in this study.
Participant recruitment for primary data collection began on 22 April 2024 and was completed on 8 October 2024. Primary data collection for follow-up will continue through up to 12 months after the date of the last enrolment.
NCT06386263.
在当前的临床实践中，乳腺癌根据激素受体和人表皮生长受体2（HER2）表达状态进行治疗，这些指标在疾病管理和总体预后中起着重要作用。曲妥珠单抗德曲妥珠单抗（T-DXd）已在多项全球前瞻性DESTINY-乳腺癌试验中进行了研究。加拿大卫生部最近已批准T-DXd用于HER2阳性乳腺癌患者，这些患者曾接受过曲妥珠单抗恩美曲妥珠单抗治疗，或在转移性环境中至少接受过一种基于抗HER2的治疗方案，或在新辅助或辅助治疗中接受过基于抗HER2的治疗方案并在完成新辅助或辅助治疗期间或之后6个月内出现疾病复发。T-DXd也适用于HER2低表达、不可切除和/或转移性乳腺癌（mBC）患者，这些患者在转移性环境中至少接受过一线化疗，或在完成辅助化疗期间或之后6个月内出现疾病复发。然而，在真实世界环境中评估T-DXd的证据很少。因此，本研究的总体目标是为接受T-DXd治疗的HER2阳性和HER2低表达mBC患者的停药和治疗调整生成加拿大真实世界证据。
这是一项混合纵向队列研究设计，利用患者支持计划（PSP）的二级数据以及额外的原始数据收集，以评估接受T-DXd治疗的HER2阳性和HER2低表达mBC患者的研究治疗相关结果。主要而言，本研究将利用PSP的二级数据，其中将包括临床和人口统计学特征以及患者在参加PSP期间的治疗持续时间、调整和强度信息。这些数据将辅以原始数据，原始数据将通过患者问卷收集，包括PSP中未涵盖的其他自我报告的临床和人口统计学特征，包括接受治疗的随访数据、PSP关闭后的治疗停药信息以及CT扫描和心脏监测扫描的频率。
该研究方案于2023年12月13日获得Advarra机构审查委员会批准（编号：D133HR00037）。研究结果将通过在同行评审期刊上发表、面向不同受众的口头和海报展示、网站和科学会议进行传播。在所有患者同意参与本研究之前，将获得他们的书面知情同意。
原始数据收集的参与者招募于2024年4月22日开始，并于2024年10月8日完成。随访的原始数据收集将持续到最后一名参与者入组日期后的12个月。
NCT06386263。
