Division of Hematology-Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, 82, Gumi-Ro, Bundang-Gu, Seongnam, 13620, Republic of Korea.
Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University, College of Medicine, Seoul, Republic of Korea.
Cancer Immunol Immunother. 2024 Aug 6;73(10):197. doi: 10.1007/s00262-024-03782-7.
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).
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.
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).
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.
目前尚无预测乳腺癌患者免疫治疗和化疗联合反应的生物标志物。在这项研究中，我们报告了 II 期临床试验中曲贝替定联合纳武利尤单抗治疗 HER-2 阴性转移性乳腺癌（KORNELIA 试验，NCT04061863）患者预处理肿瘤组织的探索性基因组和转录组分析。
我们分析了基于基因组（n=76）和转录组数据（n=58）的肿瘤分子谱与治疗疗效之间的相关性。无进展生存期（PFS）≥6 个月的患者定义为 PFS6 应答者，否则为 PFS6 无应答者。
肿瘤突变负荷（TMB）分析显示对疗效有一定的有利影响，而与同源重组缺陷（HRD）相关的几项分析表明对疗效可能有负面影响。携带 TP53 突变的患者 PFS6 率和 PFS 显著较差，这与 PFS6 无应答者中细胞周期相关特征的富集相关。抗原呈递基因集富集评分（≥中位数）较高与 PFS 延长显著相关。长反应者（≥18 个月）的幼稚 B 细胞和浆细胞比例明显更高。
包括 TMB、HRD 和 TP53 突变在内的基因组特征以及与免疫细胞特征和细胞周期相关的转录组特征可能有助于区分应答者。我们的研究结果为进一步探索该联合方案及其在这些肿瘤中的生物标志物提供了思路。
