我们先前报告了一项Ⅱ期临床试验的结果，该试验使用抗PD-1抗体联合抗血管内皮生长因子受体2抑制剂和厄立必利用于晚期经过多次治疗的三阴性乳腺癌患者，并取得了令人满意的客观缓解率（ORR）为37.0％（NCT04303741）。在这里，我们报告了该研究的更新生存结果和血清代谢物变化。采用质子核磁共振波谱分析检测代谢物动态变化，并探索反应的生物标志物。我们发现治疗敏感的患者在基线时具有较高的非常低密度脂蛋白相关代谢物表达。由六种代谢物构成的脂质蛋白组学模型在预测6个月ORR和无进展生存率方面的受试者工作特征曲线下面积分别为0.88和0.87。治疗抵抗的患者在治疗后血清中丙氨酸和肌氨酸浓度显著升高。总之，我们建立了一个由六种代谢物组成的模型，用于识别更从三联疗法中获益的患者，并丙氨酸和肌氨酸可能与治疗抵抗有关。© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

We previously reported the results of a phase II trial of anti-PD-1 antibody plus anti-vascular endothelial growth factor receptor 2 inhibitors and eribulin in heavily pretreated advanced triple-negative breast cancer with a favorable objective response rate (ORR) of 37.0% (NCT04303741). Here we report updated survival outcomes and serum metabolite changes of the study. Proton nuclear magnetic resonance spectroscopy was used to detect metabolite dynamics and explore biomarkers for response. We found that treatment-sensitive patients had higher very low-density lipoprotein-related metabolite expression at baseline. A lipid proteomics model consisting of six metabolites predicted ORR and progression-free survival at 6 months with area under the receiver operating characteristic curves of 0.88 and 0.87, respectively. Serum asparagine and sarcosine concentrations were significantly higher after treatment in treatment-resistant patients. In conclusion, we constructed a model consisting of six metabolites to identify patients who benefit more from the triplet treatment, and asparagine and sarcosine may be associated with treatment resistance.© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.