Nature communications, 2021-09, Vol.12 (1), p.5563-13, Article 5563
- Keenan, Tanya E.
- Guerriero, Jennifer L.
- Barroso-Sousa, Romualdo
- Li, Tianyu
- O’Meara, Tess
- Giobbie-Hurder, Anita
- Tayob, Nabihah
- Hu, Jiani
- Severgnini, Mariano
- Agudo, Judith
- Vaz-Luis, Ines
- Anderson, Leilani
- Attaya, Victoria
- Park, Jihye
- Conway, Jake
- He, Meng Xiao
- Reardon, Brendan
- Shannon, Erin
- Wulf, Gerburg
- Spring, Laura M.
- Jeselsohn, Rinath
- Krop, Ian
- Lin, Nancy U.
- Partridge, Ann
- Winer, Eric P.
- Mittendorf, Elizabeth A.
- Liu, David
- Van Allen, Eliezer M.
- Tolaney, Sara M.
2021
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- Autor(en) / Beteiligte
- Keenan, Tanya E.
- Guerriero, Jennifer L.
- Barroso-Sousa, Romualdo
- Li, Tianyu
- O’Meara, Tess
- Giobbie-Hurder, Anita
- Tayob, Nabihah
- Hu, Jiani
- Severgnini, Mariano
- Agudo, Judith
- Vaz-Luis, Ines
- Anderson, Leilani
- Attaya, Victoria
- Park, Jihye
- Conway, Jake
- He, Meng Xiao
- Reardon, Brendan
- Shannon, Erin
- Wulf, Gerburg
- Spring, Laura M.
- Jeselsohn, Rinath
- Krop, Ian
- Lin, Nancy U.
- Partridge, Ann
- Winer, Eric P.
- Mittendorf, Elizabeth A.
- Liu, David
- Van Allen, Eliezer M.
- Tolaney, Sara M.
- Titel
- Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer
- Ist Teil von
- Nature communications, 2021-09, Vol.12 (1), p.5563-13, Article 5563
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-021-25769-zTitel-ID: cdi_doaj_primary_oai_doaj_org_article_d25f24d7eb06482f96ec27595b0111bc
- Format
- –
- Schlagworte
- 38/39, 38/91, 45/23, 631/67/1347, 692/699/67/1347, Adult, Aged, Antibodies, Monoclonal, Humanized - therapeutic use, Antigen presentation, Antigen Presentation - genetics, Antigens, Antineoplastic Combined Chemotherapy Protocols - therapeutic use, B7-H1 Antigen - metabolism, Biomarkers, Breast cancer, Breast Neoplasms - drug therapy, Breast Neoplasms - genetics, Breast Neoplasms - immunology, Breast Neoplasms - mortality, Cytokines, Cytokines - blood, Cytokines - immunology, Drug Resistance, Neoplasm - genetics, Estrogens, Estrogens - metabolism, Female, Furans - therapeutic use, Gene Expression Profiling, Genetic Heterogeneity, Genome, Human - genetics, Genomics, Heterogeneity, Humanities and Social Sciences, Humans, Immune checkpoint inhibitors, Immune Checkpoint Inhibitors - therapeutic use, Immunoregulation, Immunotherapy, Ketones - therapeutic use, Lymphocytes, Tumor-Infiltrating - immunology, Metastases, Metastasis, Middle Aged, Monoclonal antibodies, multidisciplinary, Mutation, Neoplasm Metastasis, Patients, Pembrolizumab, Receptors, Receptors, Estrogen - metabolism, Receptors, Progesterone - metabolism, Science, Science (multidisciplinary), Signal Transduction - genetics, Survival Rate, Targeted cancer therapy, Toxicity, Treatment Outcome, Tumors