Biomarkers of response to camrelizumab combined with apatinib: an analysis from a phase II trial in advanced triple-negative breast cancer patients
- 25 February 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Breast Cancer Research and Treatment
- Vol. 186 (3), 687-697
- https://doi.org/10.1007/s10549-021-06128-4
Abstract
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.Keywords
Funding Information
- Natural Science Foundation of China Grant (81630074, 81872141)
- Guangzhou Science and Technology Plan Key Projects (201804020076)
- Fundamental Research Funds for the Central Universities (20ykpy101)
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