Author:
Park Changhee,Suh Koung Jin,Kim Se Hyun,Lee Kyung-Hun,Im Seock-Ah,Kim Min Hwan,Sohn Joohyuk,Jeong Jae Ho,Jung Kyung Hae,Lee Kyoung Eun,Park Yeon Hee,Kim Hee-Jun,Cho Eun Kyung,Choi In Sil,Noh Seung-Jae,Shin Inkyung,Cho Dae-Yeon,Kim Jee Hyun
Abstract
Abstract
Background
Biomarkers for predicting response to the immunotherapy and chemotherapy combination in breast cancer patients are not established. In this study, we report exploratory genomic and transcriptomic analyses of pretreatment tumor tissues from patients enrolled in phase II clinical trial of a combination of eribulin and nivolumab for HER-2-negative metastatic breast cancer (MBC) (KORNELIA trial, NCT04061863).
Methods
We analyzed associations between tumor molecular profiles based on genomic (n = 76) and transcriptomic data (n = 58) and therapeutic efficacy. Patients who achieved progression-free survival (PFS) ≥ 6 months were defined as PFS6-responders and PFS6-nonresponders otherwise.
Findings
Analyses on tumor mutation burden (TMB) showed a tendency toward a favorable effect on efficacy, while several analyses related to homologous recombination deficiency (HRD) indicated a potentially negative impact on efficacy. Patients harboring TP53 mutations showed significantly poor PFS6 rate and PFS, which correlated with the enrichment of cell cycle-related signatures in PFS6-nonresponders. High antigen presentation gene set enrichment scores (≥ median) were significantly associated with longer PFS. Naïve B-cell and plasma cell proportions were considerably higher in long responders (≥ 18 months).
Interpretation
Genomic features including TMB, HRD, and TP53 mutations and transcriptomic features related to immune cell profiles and cell cycle may distinguish responders. Our findings provide insights for further exploring the combination regimen and its biomarkers in these tumors.
Funder
Ministry of Health and Welfare, Republic of Korea
Seoul National University Bundang Hospital
Publisher
Springer Science and Business Media LLC
Cited by
1 articles.
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