{"title":"Efficacy and immune-related adverse events of pembrolizumab with bone-modifying agents in female patients with breast cancer.","authors":"Alexis LeVee, Esther Peluso, Melissa G Lechner, Nora Ruel, Joanne Mortimer, Irene Kang, Karen Tsai","doi":"10.1093/oncolo/oyaf134","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Emerging studies demonstrate that some bone-modifying agents (BMAs), such as denosumab (Dmab), can modulate immune responses by increasing tumor-infiltrating T cells and expanding the T-cell repertoire. Female patients with breast cancer in particular often receive concurrent treatment with immune checkpoint inhibitors (ICI) and BMAs. However, the clinical impact of BMAs on immune-related adverse events (irAE) and cancer outcomes in patients treated with ICI remains poorly understood.</p><p><strong>Materials and methods: </strong>Female patients with breast cancer treated with pembrolizumab between 2017 and 2024 were included. Patients were categorized according to BMA received: zoledronic acid (ZA), Dmab, or none. BMA therapy was considered received within a dose interval prior to ICI (12 months for ZA; 6 months for Dmab), during ICI therapy, or within 1 month of the last ICI dose.</p><p><strong>Results: </strong>In a cohort of 425 female patients with breast cancer treated with pembrolizumab, 55 (12.9%) received Dmab, 31 (7.3%) received ZA, and 339 (80.0%) received no BMA. A total of 255 (60%) patients had early-stage breast cancer, and 170 (40%) had metastatic disease. After a median follow-up of 19.4 months (95% CI, 17.5-20.8), the incidence of severe irAE was higher in patients who received Dmab vs those who received no BMA (21.8% vs 11.5%, P = .04). Patients who received Dmab had higher responses (48.0%) compared to those who received ZA (31.6%) and no BMA (35.0%), although not statistically significant (P = .3).</p><p><strong>Conclusion: </strong>This is the first study to suggest an increased rate of severe irAE and potential synergistic anti-tumor effect of Dmab in combination with ICI in female patients with breast cancer.</p>","PeriodicalId":54686,"journal":{"name":"Oncologist","volume":"30 6","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12205979/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oncologist","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/oncolo/oyaf134","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Emerging studies demonstrate that some bone-modifying agents (BMAs), such as denosumab (Dmab), can modulate immune responses by increasing tumor-infiltrating T cells and expanding the T-cell repertoire. Female patients with breast cancer in particular often receive concurrent treatment with immune checkpoint inhibitors (ICI) and BMAs. However, the clinical impact of BMAs on immune-related adverse events (irAE) and cancer outcomes in patients treated with ICI remains poorly understood.
Materials and methods: Female patients with breast cancer treated with pembrolizumab between 2017 and 2024 were included. Patients were categorized according to BMA received: zoledronic acid (ZA), Dmab, or none. BMA therapy was considered received within a dose interval prior to ICI (12 months for ZA; 6 months for Dmab), during ICI therapy, or within 1 month of the last ICI dose.
Results: In a cohort of 425 female patients with breast cancer treated with pembrolizumab, 55 (12.9%) received Dmab, 31 (7.3%) received ZA, and 339 (80.0%) received no BMA. A total of 255 (60%) patients had early-stage breast cancer, and 170 (40%) had metastatic disease. After a median follow-up of 19.4 months (95% CI, 17.5-20.8), the incidence of severe irAE was higher in patients who received Dmab vs those who received no BMA (21.8% vs 11.5%, P = .04). Patients who received Dmab had higher responses (48.0%) compared to those who received ZA (31.6%) and no BMA (35.0%), although not statistically significant (P = .3).
Conclusion: This is the first study to suggest an increased rate of severe irAE and potential synergistic anti-tumor effect of Dmab in combination with ICI in female patients with breast cancer.
期刊介绍:
The Oncologist® is dedicated to translating the latest research developments into the best multidimensional care for cancer patients. Thus, The Oncologist is committed to helping physicians excel in this ever-expanding environment through the publication of timely reviews, original studies, and commentaries on important developments. We believe that the practice of oncology requires both an understanding of a range of disciplines encompassing basic science related to cancer, translational research, and clinical practice, but also the socioeconomic and psychosocial factors that determine access to care and quality of life and function following cancer treatment.