Biomarkers of response to camrelizumab combined with apatinib: an analysis from a phase II trial in advanced triple-negative breast cancer patients
Biomarkers of response to camrelizumab combined with apatinib: an analysis from a phase II trial in advanced triple-negative breast cancer patients
复制标题
卡瑞利珠单抗联合阿帕替尼反应的生物标志物：晚期三阴性乳腺癌患者的 II 期试验分析。
DOI：
10.1007/s10549-021-06128-4
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发表时间：
2021-02-25
影响因子：
3.8
通讯作者：
Liu, Qiang
中科院分区：
文献类型：
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作者：
Liu, Jieqiong;Li, Ying;Liu, Qiang
目的 我们最近报道了一项 II 期试验的结果，表明卡瑞利珠单抗联合阿帕替尼在晚期三阴性乳腺癌 (TNBC) 中的客观缓解率 (ORR) 达到 43.3%。这项研究对潜在的生物标志物进行了分析。方法采用免疫组织化学法检测肿瘤样本中TILs、CD8(+) T细胞和PD-1/PD-L1的表达。通过多重微珠免疫分析或流式细胞术分析血液样本中的 59 种细胞因子/趋化因子、生长因子或检查点相关蛋白、血液免疫细胞亚群。分析了生物标志物与临床结果（包括 ORR、无进展生存期 (PFS) 和总生存期 (OS)）之间的相关性。结果 28 名患者接受了活检并采集了血液。基线 TIL 与较长的 PFS 显着相关 (P = 0.035)。治疗期间肿瘤浸润 CD8+ T 细胞增加 > 15% 与较高的 ORR 相关（P = 0.040）。 HGF 或 IL-8 基线血浆水平较低的患者更有可能对治疗产生反应（分别为 P = 0.005 或 0.001），并且表现出更长的 PFS 和 OS。治疗期间 IL-8 降低或 TIM-3 或 CD152 升高的患者对治疗的反应更大（分别为 P = 0.008、0.040 或 0.014）。应答者血液中的基线 CD4(+) T 细胞和 B 细胞比例高于无应答者（P 分别为 0.002 和 0.030）。结论 治疗期间基线TIL较高或肿瘤浸润CD8(+)T细胞增加较多、血浆HGF/IL-8基线较低、血浆IL-8减少、治疗期间血浆TIM-3/CD152增加、血液中基线CD4(+)T细胞或B细胞比例较高是晚期TNBC患者抗血管生成和免疫联合治疗的潜在生物标志物。
Purpose We recently reported results of a phase II trial that camrelizumab plus apatinib induced an objective response rate (ORR) at 43.3% in advanced triple-negative breast cancer (TNBC). This study presents analysis of potential biomarkers. Methods TILs, CD8(+) T cells and PD-1/PD-L1 expression were evaluated in tumor samples by immunohistochemistry. 59 Cytokines/chemokines, growth factors, or checkpoint-related proteins, blood immune cell subpopulations were analyzed in blood samples by multiplexed bead immunoassays or flow cytometry. Correlation between biomarkers and clinical outcomes including ORR, progression-free survival (PFS), and overall survival (OS) was analyzed. Results 28 Patients had biopsies and blood collected. Baseline TILs were significantly associated with longer PFS (P = 0.035). An increase of tumor-infiltrating CD8(+) T cells > 15% during therapy was associated with higher ORR (P = 0.040). Patients with lower baseline plasma levels of HGF or IL-8 were more likely to respond to treatment (P = 0.005 or 0.001, respectively), and showed a longer PFS and OS. Patients with a decrease of IL-8, or an increase of TIM-3 or CD152 during treatment responded more to treatment (P = 0.008, 0.040, or 0.014, respectively). Responders had a higher baseline CD4(+) T cells and B cell proportions in blood than non-responders (P = 0.002 and 0.030, respectively). Conclusion Higher baseline TILs or a greater increase of tumor-infiltrating CD8(+) T cells during therapy, lower baseline plasma HGF/IL-8, a decrease of plasma IL-8, an increase of plasma TIM-3/CD152 during therapy, higher baseline CD4(+) T cells or B cells proportion in blood are potential biomarkers for combinational anti-angiogenesis and immunotherapy in advanced TNBC patients.