Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer

Tanya E. Keenan, Jennifer L. Guerriero, Romualdo Barroso-Sousa, Tianyu Li, Tess O’Meara, Anita Giobbie-Hurder, Nabihah Tayob, Jiani Hu, Mariano Severgnini, Judith Agudo, Ines Vaz-Luis, Leilani Anderson, Victoria Attaya, Jihye Park, Jake Conway, Meng Xiao He, Brendan Reardon, Erin Shannon, Gerburg Wulf, Laura M. Spring, Rinath Jeselsohn, Ian Krop, Nancy U. Lin, Ann Partridge, Eric P. Winer, Elizabeth A. Mittendorf, David Liu, Eliezer M. Van Allen () and Sara M. Tolaney ()
Additional contact information
Tanya E. Keenan: Dana-Farber Cancer Institute
Jennifer L. Guerriero: Dana-Farber Cancer Institute
Romualdo Barroso-Sousa: Dana-Farber Cancer Institute
Tianyu Li: Dana-Farber Cancer Institute, Boston
Tess O’Meara: Dana-Farber Cancer Institute
Anita Giobbie-Hurder: Dana-Farber Cancer Institute, Boston
Nabihah Tayob: Dana-Farber Cancer Institute, Boston
Jiani Hu: Dana-Farber Cancer Institute, Boston
Mariano Severgnini: Dana-Farber Cancer Institute
Judith Agudo: Dana-Farber Cancer Institute
Ines Vaz-Luis: Institut Gustave Roussy
Leilani Anderson: Dana-Farber Cancer Institute
Victoria Attaya: Dana-Farber Cancer Institute
Jihye Park: Dana-Farber Cancer Institute
Jake Conway: Dana-Farber Cancer Institute
Meng Xiao He: Dana-Farber Cancer Institute
Brendan Reardon: Dana-Farber Cancer Institute
Erin Shannon: Broad Institute of Massachusetts Institute of Technology and Harvard
Gerburg Wulf: Beth Israel Deaconess Medical Center
Laura M. Spring: Massachusetts General Hospital
Rinath Jeselsohn: Dana-Farber Cancer Institute
Ian Krop: Dana-Farber Cancer Institute
Nancy U. Lin: Dana-Farber Cancer Institute
Ann Partridge: Dana-Farber Cancer Institute
Eric P. Winer: Dana-Farber Cancer Institute
Elizabeth A. Mittendorf: Dana-Farber/Brigham and Women’s Cancer Center
David Liu: Dana-Farber Cancer Institute
Eliezer M. Van Allen: Dana-Farber Cancer Institute
Sara M. Tolaney: Dana-Farber Cancer Institute

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Immune checkpoint inhibitors (ICIs) have minimal therapeutic effect in hormone receptor-positive (HR+ ) breast cancer. We present final overall survival (OS) results (n = 88) from a randomized phase 2 trial of eribulin ± pembrolizumab for patients with metastatic HR+ breast cancer, computationally dissect genomic and/or transcriptomic data from pre-treatment tumors (n = 52) for molecular associations with efficacy, and identify cytokine changes differentiating response and ICI-related toxicity (n = 58). Despite no improvement in OS with combination therapy (hazard ratio 0.95, 95% CI 0.59–1.55, p = 0.84), immune infiltration and antigen presentation distinguished responding tumors, while tumor heterogeneity and estrogen signaling independently associated with resistance. Moreover, patients with ICI-related toxicity had lower levels of immunoregulatory cytokines. Broadly, we establish a framework for ICI response in HR+ breast cancer that warrants diagnostic and therapeutic validation. ClinicalTrials.gov Registration: NCT03051659.

Date: 2021
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DOI: 10.1038/s41467-021-25769-z

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