Department of Medicine, University of Toronto, Toronto, ON, Canada.
St. Michael's Hospital, Toronto, ON, Canada.
Breast Cancer Res Treat. 2020 May;181(1):155-165. doi: 10.1007/s10549-020-05614-5. Epub 2020 Mar 31.
Little data exist for comparing cardiac safety and survival outcomes of trastuzumab/pertuzumab or ado-T emtansine (TDM1) in metastatic breast cancer (MBC) patients enrolled in randomized clinical trial (RCT) vs the real-world.
This was a retrospective population-based cohort of all patients with MBC treated with trastuzumab/pertuzumab or TDM1 (2012-2017) in Ontario, Canada. Outcomes were incident heart failure (HF) and overall survival (OS). RCT data were obtained from digitizing survival curves and compared with cohort data using Kaplan-Meier analysis. Age-based comparison of outcomes was conducted for patients ≥ 65 years old vs younger than 65.
The two cohorts composed of 833 and 397 patients treated with trastuzumab/pertuzumab and TDM1, of whom 5.5% and 7.6% had baseline HF, respectively. Incident HF following trastuzumab/pertuzumab or TDM1 was low (trastuzumab/pertuzumab 1.8 events/100 person years; TDM1 0.02 events/100 person years). The median OS was 39.2 and 56.4 months in the trastuzumab/pertuzumab population-based cohort and CLEOPATRA, respectively. The median OS was 15.4 and 30.9 months in the TDM1 population-based cohort and EMILIA, respectively. Cohort OS was significantly worse than RCT OS (trastuzumab/pertuzumab HR 1.67, 95% CI 1.37-2.03, p < 0.0001; TDM1 HR 2.80, 95% CI 2.27-3.44, p < 0.0001). Older patients had worse OS than younger patients for trastuzumab/pertuzumab (HR 1.60, 95% CI 1.19-2.16, p = 0.0018), but not for TDM1 (HR 1.16, 95% CI 0.81-1.66, p = 0.43).
HF incidence during trastuzumab/pertuzumab or TDM1 therapy in this real-world cohort was low. Survival in this cohort was worse compared to RCT, suggesting that recruitment of patients similar to the real-world population is required.
在转移性乳腺癌（MBC）患者中，比较曲妥珠单抗/帕妥珠单抗或 ado-T 曲妥珠单抗（TDM1）的心脏安全性和生存结局的相关数据，其中包括在随机临床试验（RCT）中登记的患者和真实世界中的患者。
这是一项回顾性基于人群的队列研究，纳入了 2012 年至 2017 年期间在加拿大安大略省接受曲妥珠单抗/帕妥珠单抗或 TDM1 治疗的所有 MBC 患者。研究终点为新发心力衰竭（HF）和总生存（OS）。从生存曲线数字化中获得 RCT 数据，并通过 Kaplan-Meier 分析与队列数据进行比较。对于年龄≥65 岁的患者和年龄<65 岁的患者进行基于年龄的结局比较。
两个队列分别由 833 名和 397 名接受曲妥珠单抗/帕妥珠单抗和 TDM1 治疗的患者组成，其中分别有 5.5%和 7.6%的患者基线时存在 HF。曲妥珠单抗/帕妥珠单抗或 TDM1 治疗后新发 HF 的发生率较低（曲妥珠单抗/帕妥珠单抗为 1.8 例/100 人年；TDM1 为 0.02 例/100 人年）。在基于人群的曲妥珠单抗/帕妥珠单抗队列中，中位 OS 为 39.2 个月，在 CLEOPATRA 研究中为 56.4 个月。在基于人群的 TDM1 队列中，中位 OS 为 15.4 个月，在 EMILIA 研究中为 30.9 个月。队列 OS 明显差于 RCT OS（曲妥珠单抗/帕妥珠单抗 HR 1.67，95%CI 1.37-2.03，p<0.0001；TDM1 HR 2.80，95%CI 2.27-3.44，p<0.0001）。对于曲妥珠单抗/帕妥珠单抗，年龄较大的患者 OS 较年龄较小的患者差（HR 1.60，95%CI 1.19-2.16，p=0.0018），但对于 TDM1 并非如此（HR 1.16，95%CI 0.81-1.66，p=0.43）。
在这个真实世界的队列中，曲妥珠单抗/帕妥珠单抗或 TDM1 治疗期间 HF 的发生率较低。与 RCT 相比，该队列的生存结果较差，这表明需要招募与真实世界人群相似的患者。
