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

IF 8.3 2区医学 Q1 ONCOLOGY ESMO Open Pub Date : 2024-10-01 Epub Date: 2024-09-30 DOI:10.1016/j.esmoop.2024.103733

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

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Abstract

Background

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.

Patients and methods

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).

Results

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.

Conclusions

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.

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对HR阳性/HER2阴性、Oncotype DX复发评分≥18分的早期乳腺癌患者进行新辅助来曲唑和帕博西尼治疗：DxCARTES研究

背景在内分泌治疗中加入细胞周期蛋白依赖性激酶4和6抑制剂对分子分期的影响仍未确定。从高风险组转为低风险复发评分（RS）组可提供有用的信息，以确定哪些患者可能不需要化疗。本研究旨在评估来曲唑联合帕博西尼作为激素受体（HR）阳性/人表皮生长因子受体2（HER2）阴性、初始Oncotype DX RS≥18的早期乳腺癌患者新辅助治疗的生物学和临床活性。患者和方法参与者为年龄≥18岁、HR阳性/HER2阴性、Ki67≥20%、II-IIIB期、基线RS≥18的早期乳腺癌女性患者。治疗前RS值为18-25（队列A）和26-100（队列B）的合格患者在手术前接受来曲唑（每天2.5毫克；如果绝经前或围绝经期，加戈舍瑞林）加帕博西利（每天125毫克；3/1方案）6个28天周期的治疗。两个队列的主要终点均为手术时达到RS≤25或病理完全反应（pCR）的患者比例。结果共有67名患者入组，其中65名患者可接受主要终点评估（队列A中有32名患者，队列B中有33名患者）。手术时，A组有22名（68.8%）患者的RS值≤25，B组有18名（54.5%）患者的RS值≤25或pCR[B组仅有1名（3.0%）患者]，B组达到了主要终点（P <0.01），而A组未达到（P = 0.98）。结论对于RS≥18的患者，来曲唑加palbociclib新辅助治疗的疗效似乎与治疗前的RS无关。然而，在基线RS为26-100的HR阳性/HER2阴性早期乳腺癌患者中，约有一半的患者通过该方案实现了分子分期。

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来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.