Medical Oncology Service, Hospital General Universitario Gregorio Marañon, Universidad Complutense, Centro de Investigación Biomédica en Red-Cáncer, Grupo Español de Investigación en Cáncer de Mama, Madrid, Spain.
Clinica de Pesquisa e Centro São Paulo, São Paulo, Brazil.
JAMA Oncol. 2022 Aug 1;8(8):1190-1194. doi: 10.1001/jamaoncol.2022.1488.
Patients selected to receive neoadjuvant chemotherapy (NAC) are usually those at higher risk of relapse, and there is a need to find better therapeutic options for these patients.
To determine the efficacy and safety outcomes for patients with hormone receptor (HR)-positive, ERBB2 (formerly HER2)-, high-risk early breast cancer enrolled in the randomized clinical trial monarchE who received NAC.
DESIGN, SETTING, AND PARTICIPANTS: The monarchE randomized clinical trial was a multicenter, phase 3, open-label study that evaluated adjuvant treatment with abemaciclib plus endocrine therapy (ET) compared with ET alone in patients with HR+, ERBB2-, and node-positive early breast cancer who were at high risk of recurrence. Patients were recruited between July 2017 and August 2019 from 603 sites in 38 countries. This subgroup analysis was performed with primary outcome data, with a cutoff date of July 8, 2020.
Enrolled patients were randomized (1:1) to receive standard of care ET for at least 5 years with or without treatment with abemaciclib (150 mg, twice daily) for 2 years (treatment period) or until criteria were met for discontinuation.
Prior chemotherapy (NAC vs adjuvant vs none) was a stratification factor in monarchE, and and a prespecified exploratory analysis included outcomes in patients who received NAC. The data presented in this article are from the primary outcome analysis (395 invasive disease-free survival [IDFS] events; cutoff date, July 8, 2020; median follow-up 19 months [IQR, 15.6-23.9 months]). Invasive disease-free survival (the primary end point of monarchE) and distant relapse-free survival (DRFS) were evaluated using the Cox proportional hazard model and Kaplan-Meier method.
Of the 5637 patients (mean [SD] age, 49.9 [10.6] years; 2046 women [99.5%]; 462 Asian [22.8%], 54 Black [2.7%], and 1473 White participants [70.8%]) enrolled in monarchE, 2056 (37%) received treatment with NAC. In this subgroup, treatment with abemaciclib and ET demonstrated clinically meaningful benefit in IDFS (hazard ratio, 0.61; 95% CI, 0.47-0.80) and DRFS (hazard ratio, 0.61; 95% CI, 0.46-0.81), which corresponded with an absolute improvement of 6.6% in 2-year IDFS rates and 6.7% in 2-year DRFS rates. A consistent treatment benefit was observed across subgroups of pathological breast tumor size or number of positive lymph nodes at surgery.
In the randomized clinical trial monarchE, treatment with adjuvant abemaciclib combined with ET demonstrated a clinically meaningful improvement in IDFS and DRFS for patients with HR+, ERBB2-, node-positive, high-risk early breast cancer who received NAC before trial enrollment.
ClinicalTrials.gov Identifier: NCT03155997.
重要性：通常选择接受新辅助化疗（NAC）的患者是那些复发风险较高的患者，因此需要为这些患者寻找更好的治疗选择。
目的：评估接受随机临床试验 monarchE 中入组的激素受体（HR）阳性、ERBB2（以前称为 HER2）阳性、高危早期乳腺癌且接受 NAC 治疗的患者的疗效和安全性结局。
设计、设置和参与者：monarchE 是一项多中心、III 期、开放性研究，评估了 abemaciclib 联合内分泌治疗（ET）与 ET 单独用于 HR+、ERBB2-、淋巴结阳性且复发风险高的早期乳腺癌患者的辅助治疗。患者于 2017 年 7 月至 2019 年 8 月间在 38 个国家的 603 个地点入组。该亚组分析采用主要结局数据进行，截止日期为 2020 年 7 月 8 日。
干预措施：入组患者按 1:1 随机分配接受标准护理 ET 至少 5 年，联合或不联合 abemaciclib（150mg，每日 2 次）治疗 2 年（治疗期），直至符合停药标准。
主要结局和测量：在 monarchE 中，既往化疗（NAC 对比辅助治疗或无化疗）是分层因素，一项预设的探索性分析包括接受 NAC 治疗的患者的结局。本文中报告的数据来自主要结局分析（395 例侵袭性无病生存 [IDFS] 事件；截止日期，2020 年 7 月 8 日；中位随访时间 19 个月 [IQR，15.6-23.9 个月]）。IDFS（monarchE 的主要终点）和远处无复发生存（DRFS）采用 Cox 比例风险模型和 Kaplan-Meier 法进行评估。
结果：在 5637 例患者（平均 [SD] 年龄，49.9 [10.6] 岁；2046 例女性 [99.5%]；462 例亚洲人 [22.8%]、54 例黑人 [2.7%] 和 1473 例白人参与者 [70.8%]）中，2056 例（37%）接受 NAC 治疗。在该亚组中，abemaciclib 和 ET 联合治疗在 IDFS（风险比，0.61；95%CI，0.47-0.80）和 DRFS（风险比，0.61；95%CI，0.46-0.81）方面表现出有临床意义的获益，这与 2 年 IDFS 率提高 6.6%和 2 年 DRFS 率提高 6.7%相对应。在手术时的病理乳腺肿瘤大小或阳性淋巴结数量的亚组中观察到一致的治疗获益。
结论和相关性：在随机临床试验 monarchE 中，接受辅助 abemaciclib 联合 ET 治疗的 HR+、ERBB2-、淋巴结阳性、高危早期乳腺癌患者，在入组前接受 NAC 治疗后，在 IDFS 和 DRFS 方面有显著改善。
试验注册：ClinicalTrials.gov 标识符：NCT03155997。
