Efficacy, safety, and predictive biomarkers of neoadjuvant nab-paclitaxel and pembrolizumab in hormone receptor-positive breast cancer: A randomized pilot trial
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.
Authors
- Xochitl C. Morgan (ORCID: https://orcid.org/0000-0002-6264-6961)
- Jillian Alberti (ORCID: https://orcid.org/0009-0007-5636-6967)
- David D. Yang (ORCID: https://orcid.org/0000-0002-5146-218X)
- Yizhuo Shen (ORCID: https://orcid.org/0000-0003-4453-0719)
- Elizabeth A. Mittendorf (ORCID: https://orcid.org/0000-0002-9762-8536)
- Molly K. DiLullo (ORCID: https://orcid.org/0009-0005-1036-796X)
- Ayesha Mohammed-Abreu
- Ian E. Krop (ORCID: https://orcid.org/0000-0002-6380-5944)
- Xiangying Chu (ORCID: https://orcid.org/0009-0000-3474-3804)
- Eileen Wrabel
- Eliezer M. Van Allen (ORCID: https://orcid.org/0000-0002-0201-4444)
- Ann H. Partridge (ORCID: https://orcid.org/0000-0002-4722-4824)
- William Audeh (ORCID: https://orcid.org/0000-0002-7790-7466)
- Busem Binboga Kurt
- Rinath M. Jeselsohn (ORCID: https://orcid.org/0000-0001-7996-7529)
- Nabihah Tayob (ORCID: https://orcid.org/0000-0001-6088-167X)
- Thomas Kuntz (ORCID: https://orcid.org/0000-0002-0823-0340)
- Jingxin Fu (ORCID: https://orcid.org/0000-0002-4028-3661)
- Sara M. Tolaney (ORCID: https://orcid.org/0000-0002-5940-8671)
- S. Chen (ORCID: https://orcid.org/0000-0001-9140-194X)
- Brendan Reardon (ORCID: https://orcid.org/0000-0002-1716-5720)
- Justin Micah Balko (ORCID: https://orcid.org/0000-0002-4263-5974)
- Adrienne Gropper Waks (ORCID: https://orcid.org/0000-0001-5649-7229)
- Kevin Meli (ORCID: https://orcid.org/0000-0002-9579-3829)
- Daniel L. Abravanel (ORCID: https://orcid.org/0000-0002-0129-1618)
- Xiaopeng Sun
- Tianyu Li (ORCID: https://orcid.org/0000-0003-2324-6452)
- Jihye Park (ORCID: https://orcid.org/0000-0002-4451-2046)
- Miranda Kleijn
Institutions
- Brigham and Women's Hospital (US)
- Beth Israel Deaconess Medical Center (US)
- Harvard University (US)
- Yale Cancer Center (US)
- Yale University (US)
- Dana-Farber Cancer Institute (US)
- Dana-Farber/Harvard Cancer Center (US)
- Dana-Farber Brigham Cancer Center (US)
- Vanderbilt University Medical Center (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-28
- DOI
- https://doi.org/10.1038/s41467-025-66667-y
- Citations
- 1
- Primary Topic
- Breast Cancer Treatment Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.94
Funders
- Dana-Farber/Harvard Cancer Center
- National Cancer Institute