HR阳性/HER2阴性早期乳腺癌患者加用来曲唑和帕博昔单抗的新辅助治疗及Oncotype DX复发风险评分≥18：DxCARTES研究

Neoadjuvant letrozole and palbociclib in patients with HR-positive/HER2-negative early breast cancer and Oncotype DX Recurrence Score ≥18: DxCARTES study

ESMO Open

影响因子:8.3

分区:医学1区 Top / 肿瘤学2区

发表日期:2024 Oct

作者: Á Guerrero-Zotano, J M Pérez-García, M Ruiz-Borrego, B Bermejo, M Gil-Gil, J de la Haba, E Alba Conejo, V Quiroga, V Carañana, A Urruticoechea, S Morales, M Bellet, A Antón, M Fernández-Abad, P Sánchez-Rovira, L Calabuig, J Pérez-Escuredo, M Sampayo-Cordero, J Cortés, A Llombart-Cussac

DOI: 10.1016/j.esmoop.2024.103733

摘要

在内分泌治疗中加入环素依赖激酶4和6抑制剂在分子分期方面的效果尚未确定。从高风险转变为低风险的复发评分（RS）组，可能提供有用信息以识别可能不需要化疗的患者。本研究旨在评估来曲唑加帕博昔单抗作为新辅助治疗在患有激素受体（HR）阳性/HER2阴性、初始Oncotype DX RS≥18的早期乳腺癌患者中的生物学和临床活性。参与者为年龄≥18岁的女性，患有HR阳性/HER2阴性、Ki67≥20%、II-III期早期乳腺癌，基线RS≥18。符合条件的患者根据预处理RS在18-25（队列A）和26-100（队列B）之间，接受六个28天的周期来曲唑（每日2.5 mg；围绝经期前或围绝经期女性加用戈舍瑞林）加帕博昔单抗（每日125 mg，3/1方案），直至手术。两组的主要终点均为手术时RS≤25或完全病理缓解（pCR）的患者比例。共纳入67名患者，其中65名可评估主要终点（队列A 32名，队列B 33名）。在手术时，队列A中有22名（68.8%）患者和队列B中有18名（54.5%）患者达到了RS≤25或pCR（队列B中仅1名，3.0%），队列B达到主要终点（P<0.01），而队列A未达到（P=0.98）。未发现新的安全信号。结果显示，在RS≥18的患者中，来曲唑加帕博昔单抗的新辅助治疗效果似乎不依赖于预处理RS。然而，基线RS在26-100的HR阳性/HER2阴性早期乳腺癌患者中约有一半通过该方案实现了分子分期的下降。

Abstract

The effect of the addition of cyclin-dependent kinases 4 and 6 inhibitors to endocrine therapy in terms of molecular downstaging remains undetermined. Switching from a high-risk to a low risk Recurrence Score (RS) group could provide useful information to identify patients who might not require chemotherapy. The purpose of this study was to assess the biological and clinical activity of letrozole plus palbociclib as neoadjuvant treatment for patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with an initial Oncotype DX RS ≥18.Participants were women aged ≥18 years with HR-positive/HER2-negative, Ki67 ≥ 20%, stage II-IIIB early breast cancer with a baseline RS ≥18. Eligible patients with a pretreatment RS 18-25 (cohort A) and 26-100 (cohort B) received six 28-day cycles of letrozole (2.5 mg per day; plus goserelin if pre- or perimenopausal) plus palbociclib (125 mg per day; 3/1 schedule) before surgery. The primary endpoint for both cohorts was the proportion of patients who achieved an RS ≤25 at surgery or a pathological complete response (pCR).A total of 67 patients were enrolled, among which 65 were assessable for the primary endpoint (32 patients in cohort A and 33 in cohort B). At surgery, 22 (68.8%) patients in cohort A and 18 (54.5%) patients in cohort B had an RS ≤25 or a pCR [only 1 (3.0%) patient in cohort B], meeting the primary endpoint in cohort B (P < 0.01), but not in cohort A (P = 0.98). No new safety signals were identified.The efficacy of neoadjuvant treatment with letrozole plus palbociclib does not seem to depend on pretreatment RS for patients with RS ≥18. However, around half of patients with HR-positive/HER2-negative early breast cancer with an RS 26-100 at baseline achieved molecular downstaging with this regimen.