lnstituto Valenciano de Oncología, Valencia.
International Breast Cancer Center (IBCC), Pangaea Oncology, Quiron Group, Barcelona, Spain; Medica Scientia Innovation Research (MEDSIR) - Oncoclínicas&Co, Jersey City (New Jersey, USA), Sao Paulo (Brazil).
ESMO Open. 2024 Oct;9(10):103733. doi: 10.1016/j.esmoop.2024.103733. Epub 2024 Sep 30.
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.
添加细胞周期蛋白依赖性激酶 4 和 6 抑制剂对内分泌治疗的分子降期作用仍不确定。从高风险组切换到低风险复发评分（RS）组可能提供有用的信息，以识别可能不需要化疗的患者。本研究的目的是评估来曲唑联合哌柏西利作为新辅助治疗对初始 Oncotype DX RS≥18 的激素受体（HR）阳性/人表皮生长因子受体 2（HER2）阴性早期乳腺癌患者的生物学和临床活性。
参与者为年龄≥18 岁的 HR 阳性/HER2 阴性、Ki67≥20%、II 期-IIIB 期早期乳腺癌患者，基线 RS≥18。有预处理 RS 18-25（队列 A）和 26-100（队列 B）的合格患者接受六个 28 天周期的来曲唑（每天 2.5 毫克；如果是绝经前或围绝经期，则加用戈舍瑞林）加哌柏西利（每天 125 毫克；3/1 方案），然后进行手术。两个队列的主要终点均为手术时 RS≤25 或病理完全缓解（pCR）的患者比例。
共纳入 67 例患者，其中 65 例可评估主要终点（队列 A 32 例，队列 B 33 例）。手术时，队列 A 中有 22 例（68.8%）患者和队列 B 中有 18 例（54.5%）患者的 RS≤25 或 pCR[仅队列 B 中有 1 例（3.0%）患者]达到了主要终点，队列 B 达到了主要终点（P<0.01），但队列 A 没有达到（P=0.98）。未发现新的安全信号。
来曲唑联合哌柏西利新辅助治疗的疗效似乎不依赖于 RS≥18 患者的预处理 RS。然而，基线 RS 为 26-100 的 HR 阳性/HER2 阴性早期乳腺癌患者约有一半可通过该方案实现分子降期。
