Safety And Immunologic Activity Of Anakinra In Her2-Negative Metastatic Breast Cancer (Mbc).
JOURNAL OF CLINICAL ONCOLOGY(2016)
摘要
e14565 Background: Higher intratumoral IL-1b levels correspond with advanced stages of MBC. We hypothesized that anakinra (Ank), an IL-1R antagonist, may decrease tumor inflammation and improve outcomes in MBC patients (pts). Methods: Eleven pts with HER2– MBC received nab paclitaxel (n = 3), eribulin (n = 5) or capecitabine (n = 2) along with Ank daily following 2 week treatment with Ank only. One pt had progressive MBC prior to chemotherapy and received Ank for 14 days. Blood was collected prior to Ank treatment, then at 2 weeks, then monthly for 6 months (mos). 11 healthy controls were included. Whole blood mRNA transcripts were captured and hybridized to 579 immune-related probes and 15 housekeeping genes using the Nanostring nCounter Human Immunology V2 panel. A linear mixed model was used to query differences in gene expression between baseline, post Ank treatment and at each time point in pts vs controls while accounting for the longitudinal study design. Differentially expressed transcripts were annotated using a modular framework analysis strategy (Chaussabel, Immunity 29:150, 2008). Results: Median age: 44 yrs; Median number of prior cytotoxic regimens for MBC: 1; Sites of metastases: bone 91%; liver 27%; lung 46%. Median duration on Ank: 4 mos (range: 11-179 days); 8/11 pts had grade 1-2 Ank injection site reactions. Gene expression analyses revealed down-regulation of T cell/cytotoxic-related transcripts and upregulation of PD-L1 and innate myeloid inflammation-related transcripts at baseline compared to controls. At month 1 post-initiation of Ank treatment, a transcriptional program characterized by down-regulation of IL1- and TLR-related transcripts and upregulation of dendritic cell differentiation transcripts was evident. This profile, together with progressive upregulation of cytotoxic/NK cell-related transcripts, was maintained at 1-6 mos follow-up. Conclusions: Ank given during chemotherapy is safe and effective at down-modulating innate inflammation and upregulating cytotoxic/NK cell transcriptional pathways in MBC pts. Further evaluation of anakinra in MBC is warranted. Clinical trial information: NCT01802970.
更多查看译文
关键词
breast cancer,anakinra,immunologic activity
AI 理解论文
溯源树
样例
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要