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

Adrienne G. Waks, Jingxin Fu, Xiangying Chu, Busem Binboga Kurt, Tianyu Li, Thomas M. Kuntz, Yizhuo Shen, David Yang, Kevin Meli, Brendan Reardon, Jihye Park, Ann Partridge, Daniel Abravanel, Rinath Jeselsohn, Eileen Wrabel, Jillian Alberti, Molly DiLullo, Serenity 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 and Sara M. Tolaney ()
Additional contact information
Adrienne G. Waks: Dana-Farber Cancer Institute, Medical Oncology
Jingxin Fu: Dana-Farber Cancer Institute, Medical Oncology
Xiangying Chu: Dana-Farber Cancer Institute, Department of Data Sciences
Busem Binboga Kurt: Dana-Farber Cancer Institute, Medical Oncology
Tianyu Li: Dana-Farber Cancer Institute, Medical Oncology
Thomas M. Kuntz: Harvard TH Chan School of Public Health, Harvard Chan Microbiome Analysis Core
Yizhuo Shen: Harvard Medical School
David Yang: Dana-Farber Cancer Institute, Medical Oncology
Kevin Meli: Dana-Farber Cancer Institute, Medical Oncology
Brendan Reardon: Dana-Farber Cancer Institute, Medical Oncology
Jihye Park: Dana-Farber Cancer Institute, Medical Oncology
Ann Partridge: Dana-Farber Cancer Institute, Medical Oncology
Daniel Abravanel: Dana-Farber Cancer Institute, Medical Oncology
Rinath Jeselsohn: Dana-Farber Cancer Institute, Medical Oncology
Eileen Wrabel: Dana-Farber Cancer Institute, Medical Oncology
Jillian Alberti: Dana-Farber Cancer Institute, Medical Oncology
Molly DiLullo: Dana-Farber Cancer Institute, Medical Oncology
Serenity Chen: Dana-Farber Brigham Cancer Center, Breast Oncology Program
Ayesha Mohammed-Abreu: Dana-Farber Cancer Institute, Medical Oncology
Xiaopeng Sun: Vanderbilt University Medical Center
Justin M. Balko: Vanderbilt University Medical Center
Miranda Kleijn: Inc., Agendia
William Audeh: Inc., Agendia
Xochitl C. Morgan: Harvard TH Chan School of Public Health, Harvard Chan Microbiome Analysis Core
Ian E. Krop: Dana-Farber Cancer Institute, Medical Oncology
Nabihah Tayob: Dana-Farber Cancer Institute, Medical Oncology
Eliezer M. Van Allen: Dana-Farber Cancer Institute, Medical Oncology
Elizabeth A. Mittendorf: Dana-Farber Brigham Cancer Center, Breast Oncology Program
Sara M. Tolaney: Dana-Farber Cancer Institute, Medical Oncology

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract 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

Date: 2025
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DOI: 10.1038/s41467-025-66667-y

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