Efficacy, safety, and predictive biomarkers of neoadjuvant nab-paclitaxel and pembrolizumab in hormone receptor-positive breast cancer: A randomized pilot trial

作者：Adrienne G. Waks, Jingxin Fu, Xiangying Chu, Busem Binboğa Kurt, Tianyu Li, Thomas Kuntz, Yizhuo Shen, David D. Yang, Kevin Meli, Brendan Reardon, Jihye Park, Ann H. Partridge, Daniel L. Abravanel, Rinath Jeselsohn, Eileen Wrabel, Jillian Alberti, Molly DiLullo, S. Chen, Ayesha Mohammed-Abreu, Xiaopeng Sun, Justin M. Balko, Miranda Kleijn, William Audeh, Xochitl C. Morgan, Ian E. Krop, Nabihah Tayob, Eliezer M. Van Allen, Elizabeth A. Mittendorf, Sara M. Tolaney · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-66667-y · 被引用次数：5 · 研究领域：Breast Cancer Treatment Studies、Cancer Immunotherapy and Biomarkers、Advanced Breast Cancer Therapies

Patients with hormone receptor-positive (HR + )/HER2- breast cancer may benefit from neoadjuvant immune checkpoint inhibitor (ICI) plus chemotherapy. The effect of chemotherapy or ICI run-in before combination therapy in this population is unexplored. In this randomized pilot trial, patients with HR + /HER2- breast cancer received two weeks of neoadjuvant nab-paclitaxel or pembrolizumab, with baseline and post-run-in tumor biopsy, followed by combined nab-paclitaxel/pembrolizumab. The primary endpoint was PD-L1 expression change between biopsies. Tumor whole exome/RNA sequencing were performed. Of 29 patients, 72% were node-positive. Residual cancer burden (RCB) 0-1 rate was 28% (inclusive of patients receiving additional neoadjuvant adriamycin/cyclophosphamide). No significant change in PD-L1 expression occurred following nab-paclitaxel or pembrolizumab run-in, thus the primary endpoint was not met. Other secondary outcome measures included overall response rate of 80% to the neoadjuvant regimen, and 3-year event-free survival of 86% (95% CI 69-100%); there were no unexpected safety signals. In exploratory biomarker analyses, higher baseline PD-L1 expression and inflammatory gene signatures were associated with favorable response (RCB 0-1); higher expression of estrogen response genes, with unfavorable response (RCB 2-3). Clinical Trial Number: NCT02999477 Despite often being poorly immunogenic, some subsets of patients with hormone receptor-positive, HER2-negative (HR + /HE...