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Biomarkers of response to camrelizumab combined with apatinib: an analysis from a phase II trial in advanced triple-negative breast cancer patients

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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.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

Consent for publication

Not applicable.

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Acknowledgements

We thank the patients and their families, nurses, trial coordinators, radiologists and pathologists who participated in this trial.

Funding

This work was supported by Grants from Natural Science Foundation of China Grants (81630074, 81872141), Guangzhou Science and Technology Plan Key Projects (201804020076) and the Fundamental Research Funds for the Central Universities (20ykpy101).

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Author notes

  1. Jieqiong Liu and Ying Li have contributed equally

Authors and Affiliations

  1. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Yanjiang West Road 107#, Guangzhou, 510120, China

    Jieqiong Liu, Ying Li, Qian Li & Qiang Liu

  2. Genecast Precision Medicine Technology Institute, Beijing, China

    Dandan Liang

  3. Jiangsu Hengrui Medicine Co., Ltd., Lianyungang, Jiangsu, China

    Quanren Wang

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  1. Jieqiong Liu
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Contributions

Conceptualization, QL; Formal analysis, JL, YL and QL; Methodology, JL, YL and QL; Project administration, QL; Writing: original draft, JL, YL and QL; Writing: review and editing, JL, YL, QL, DL, QW and QL.

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Correspondence to Jieqiong Liu or Qiang Liu.

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Research involving human participants and/or animals

This research was approved by the Clinical Research Ethics Committee of Sun Yat-sen Memorial Hospital of Sun Yat-sen University. And all the studies were performed in accordance with the International Ethical Guidelines for Biomedical Research Involving Human Subjects (CIOMS).

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Written informed consents were obtained from the participants before sampling.

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Supplementary Information

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10549_2021_6128_MOESM1_ESM.tif

(TIF 132 kb) Supplementary Fig. S1 Changes of proportions of blood immune cells and associations of baseline bloodimmune cell subpopulations and clinical outcomes. a CD4+ T cells change during treatment, b overallsurvival stratified by baseline CD4+ T cells level, c B cells change during treatment, and d progression-freesurvival stratified by baseline B cells level

10549_2021_6128_MOESM2_ESM.tif

(TIF 3542 kb) Supplementary Fig. S2 Changes of proportions of blood immune cell subpopulations during treatment. aNK cells, b PD-1+CD4+ T cells, and c PD-1+CD8+ T cells

(DOCX 17 kb)

(XLSX 33 kb) Supplementary Table S3 Results from the Procarta Panels of 59 proteins

(DOCX 18 kb)

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Liu, J., Li, Y., Li, Q. et al. Biomarkers of response to camrelizumab combined with apatinib: an analysis from a phase II trial in advanced triple-negative breast cancer patients. Breast Cancer Res Treat 186, 687–697 (2021). https://doi.org/10.1007/s10549-021-06128-4

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