Journal
NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-25769-z
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Funding
- National Institutes of Health [T32CA009172, T32 GM008313]
- National Science Foundation [DGE1144152]
- Rob and Karen Hale Distinguished Chair in Surgical Oncology
- Ludwig Center at Harvard
- Merck Sharp Dohme Corp.
- Merck Oncology Translational Studies Program grant
- Dana-Farber Cancer Institute Medical Oncology grant
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This study found that the combination of eribulin and pembrolizumab did not show benefits over using pembrolizumab alone in HR+ metastatic breast cancer patients. Molecular analysis revealed that responding tumors had immune infiltration and antigen presentation features.
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. A randomized phase 2 clinical trial has recently shown no benefit of the combination eribulin and pembrolizumab over pembrolizumab alone in HR + metastatic breast cancer patients (NCT03051659). Here, the authors are reporting the final OS data and biomarker analyses on a subset of samples to analyze molecular correlates
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