Palbociclib and letrozole for hormone receptor-positive HER2-negative breast cancer with residual disease after neoadjuvant chemotherapy.

IF 6.5 2区医学 Q1 ONCOLOGY

NPJ Breast Cancer Pub Date : 2024-11-26 DOI:10.1038/s41523-024-00710-x

Sonia Pernas, Esther Sanfeliu, Guillermo Villacampa, Javier Salvador, Antonia Perelló, Xavier González, Begoña Jiménez, María Merino, Patricia Palacios, Tomás Pascual, Emilio Alba, Lorea Villanueva, Samyukta Chillara, Juan Manuel Ferrero-Cafiero, Patricia Galvan, Aleix Prat, Eva Ciruelos

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引用次数: 0

Abstract

With the incorporation of cyclin-dependent kinase inhibitors in early breast cancer (BC), a better identification of biomarkers is needed. The PROMETEO II trial aimed to evaluate the antitumor activity of palbociclib plus letrozole and to identify response biomarkers in patients with operable HR+/HER2- BC and residual disease after neoadjuvant chemotherapy (NAC). The primary endpoint was the rate of complete cell cycle arrest (CCCA), centrally determined by Ki67 ≤ 2.7% at surgery. A comprehensive translational analysis was conducted. At surgery, the CCCA rate was 59.1%, with a 44.2% decrease in Ki67 from the end of NAC. Changes in intrinsic subtypes occurred in 48% of patients, with proliferation genes suppressed, and immune genes more upregulated in tumors with CCCA. Overall, 14% of tumors were classified as PD-L1⁺ after palbociclib. Nine patients experienced grade 3 adverse events (AEs). Palbociclib showed an anti-proliferative effect, with increased immune infiltration in residual tumors with CCCA.Trial registration: Palbociclib Plus Letrozole in Hormone Receptor Positive Residual Disease After Neoadjuvant Chemotherapy (PROMETEO II) ClinicalTrial.gov number NCT04130152. Study registration; October 17, 2019.

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帕博西尼（Palbociclib）和来曲唑治疗激素受体阳性、HER2 阴性、新辅助化疗后有残留疾病的乳腺癌。

随着细胞周期蛋白依赖性激酶抑制剂在早期乳腺癌（BC）中的应用，需要更好地识别生物标志物。PROMETEO II试验旨在评估帕博西尼（palbociclib）加来曲唑（letrozole）的抗肿瘤活性，并鉴定可手术HR+/HER2- BC患者和新辅助化疗（NAC）后残留疾病患者的反应生物标志物。主要终点是细胞周期完全停滞率（CCCA），由手术时Ki67≤2.7%集中确定。该研究进行了全面的转化分析。手术时，CCCA率为59.1%，与NAC结束时相比，Ki67下降了44.2%。48%的患者内在亚型发生了变化，CCCA肿瘤的增殖基因受到抑制，免疫基因上调较多。总体而言，服用帕博西尼后，14%的肿瘤被归类为PD-L1+。9名患者出现了3级不良事件（AE）。Palbociclib具有抗增殖作用，CCCA残留肿瘤中的免疫浸润增加：Palbociclib Plus Letrozole in Hormone Receptor Positive Residual Disease After Neoadjuvant Chemotherapy (PROMETEO II) ClinicalTrial.gov number NCT04130152.研究注册；2019年10月17日。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

NPJ Breast Cancer Medicine-Pharmacology (medical)

CiteScore

10.10

自引率

1.70%

发文量

122

审稿时长

9 weeks

期刊介绍： npj Breast Cancer publishes original research articles, reviews, brief correspondence, meeting reports, editorial summaries and hypothesis generating observations which could be unexplained or preliminary findings from experiments, novel ideas, or the framing of new questions that need to be solved. Featured topics of the journal include imaging, immunotherapy, molecular classification of disease, mechanism-based therapies largely targeting signal transduction pathways, carcinogenesis including hereditary susceptibility and molecular epidemiology, survivorship issues including long-term toxicities of treatment and secondary neoplasm occurrence, the biophysics of cancer, mechanisms of metastasis and their perturbation, and studies of the tumor microenvironment.