Journal Home > Volume 2 , Issue 3
Cancer Innovation 2023, 2(3): 172-180 https://doi.org/10.1002/cai2.70
Original Article | Open Access | Issue | Published: 23 April 2023

A real-world study of immune checkpoint inhibitors in advanced triple-negative breast cancer

Show Author's Information Zheng Zhang1,  Yadi Zhang2,  Chuanling Liu1,  Jiakang Shao1,  Yimeng Chen3,  Yimin Zhu4,  Li Zhang5,  Boyu Qin4,  Ziqing Kong1,  Xixi Wang2,  Yutong Wang1,  Deqin Huang1,  Liqun Liu1,  Yuxin Zhou1,  Ran Tao5,  Zengjie Yang6( ),  Mei Liu7( ),  Weihong Zhao5 ( )
Medical School of Chinese PLA, Beijing, China
Nankai University School of Medicine, Tianjin, China
Department of Medical Oncology, Xi'an Jiaotong University, Xi'an, Shaanxi China
Department of Medical Oncology, Fifth Medical Center, General Hospital of the Chinese People's Liberation Army, Beijing, China
Department of Medical Oncology, First Medical Center, General Hospital of the Chinese People's Liberation Army, Beijing, China
Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania USA
Department of Pathology, First Medical Center, General Hospital of the Chinese People's Liberation Army, Beijing, China
Keywords:
safety, biomarkers, prognosis, efficacy evaluation, ICIs, TNBC
Cite this article:
Zhang Z, Zhang Y, Liu C, et al. A real-world study of immune checkpoint inhibitors in advanced triple-negative breast cancer. Cancer Innovation, 2023, 2(3): 172-180. https://doi.org/10.1002/cai2.70
Download citation
EndNote(RIS)
BibTeX

473

Views

15

Downloads

Citations

1

Crossref

N/A

WoS

1

Scopus

N/A

CSCD

Abstract Full text About this article
Background

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Immune checkpoint inhibitors (ICIs) have been widely used to treat various tumors and have changed the landscape of tumor management, but the data from real-world studies of ICIs for TNBC treatment remain limited. The aim of this study was to evaluate the efficacy of ICIs in the treatment of patients with advanced TNBC in a real-world setting and to explore possible correlates.

Methods

The clinical data of advanced TNBC patients who received ICI treatment in the Chinese People's Liberation Army (PLA) General Hospital were collected. Treatment responses, outcomes and adverse events (AEs) were assessed.

Results

Eighty-one patients were included in the study. The confirmed objective response rate (ORR) was 32.1%, and the disease control rate (DCR) was 64.2%. The median progression-free survival (PFS) was 4.2 months, and the median overall survival (OS) was 11.0 months. PFS and OS were longer in patients who achieved clinical benefit from ICIs and shorter in patients who received later-line ICIs and higher levels of inflammation; specifically, patients with higher TILs had longer PFS. Overall AEs were tolerable.

Conclusions

ICIs are effective in the treatment of advanced TNBC, and the adverse reactions are tolerable. A panel of biomarkers including LDH, ALP, and bNLR were identified to predict the efficacies of ICIs in TNBC treatment.


menu
Abstract
Full text
Outline
About this article

A real-world study of immune checkpoint inhibitors in advanced triple-negative breast cancer

Show Author's information Zheng Zhang1, Yadi Zhang2, Chuanling Liu1, Jiakang Shao1, Yimeng Chen3, Yimin Zhu4, Li Zhang5, Boyu Qin4, Ziqing Kong1, Xixi Wang2, Yutong Wang1, Deqin Huang1, Liqun Liu1, Yuxin Zhou1, Ran Tao5, Zengjie Yang6( ), Mei Liu7( ), Weihong Zhao5 ( )
Medical School of Chinese PLA, Beijing, China
Nankai University School of Medicine, Tianjin, China
Department of Medical Oncology, Xi'an Jiaotong University, Xi'an, Shaanxi China
Department of Medical Oncology, Fifth Medical Center, General Hospital of the Chinese People's Liberation Army, Beijing, China
Department of Medical Oncology, First Medical Center, General Hospital of the Chinese People's Liberation Army, Beijing, China
Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania USA
Department of Pathology, First Medical Center, General Hospital of the Chinese People's Liberation Army, Beijing, China

Abstract

Background

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Immune checkpoint inhibitors (ICIs) have been widely used to treat various tumors and have changed the landscape of tumor management, but the data from real-world studies of ICIs for TNBC treatment remain limited. The aim of this study was to evaluate the efficacy of ICIs in the treatment of patients with advanced TNBC in a real-world setting and to explore possible correlates.

Methods

The clinical data of advanced TNBC patients who received ICI treatment in the Chinese People's Liberation Army (PLA) General Hospital were collected. Treatment responses, outcomes and adverse events (AEs) were assessed.

Results

Eighty-one patients were included in the study. The confirmed objective response rate (ORR) was 32.1%, and the disease control rate (DCR) was 64.2%. The median progression-free survival (PFS) was 4.2 months, and the median overall survival (OS) was 11.0 months. PFS and OS were longer in patients who achieved clinical benefit from ICIs and shorter in patients who received later-line ICIs and higher levels of inflammation; specifically, patients with higher TILs had longer PFS. Overall AEs were tolerable.

Conclusions

ICIs are effective in the treatment of advanced TNBC, and the adverse reactions are tolerable. A panel of biomarkers including LDH, ALP, and bNLR were identified to predict the efficacies of ICIs in TNBC treatment.

Keywords: safety, biomarkers, prognosis, efficacy evaluation, ICIs, TNBC

References(38)

1

Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73(1):17–48. https://doi.org/10.3322/caac.21763
DOI Google Scholar
2

Hong H, Li C, Gong L, Wang J, Li D, Shi J, et al. Universal endogenous antibody recruiting nanobodies capable of triggering immune effectors for targeted cancer immunotherapy. Chem Sci. 2021;12(12):4623–30. https://doi.org/10.1039/d0sc05332e
DOI Google Scholar
3

Waks AG, Winer EP. Breast cancer treatment. JAMA. 2019;321(3):288. https://doi.org/10.1001/jama.2018.19323
DOI Google Scholar
4

Chen X, Yang M, Yin J, Li P, Zeng S, Zheng G, et al. Tumor-associated macrophages promote epithelial–mesenchymal transition and the cancer stem cell properties in triple-negative breast cancer through CCL2/AKT/β-catenin signaling. Cell Commun Signaling. 2022;20(1):92. https://doi.org/10.1186/s12964-022-00888-2
DOI Google Scholar
5

Bagegni NA, Davis AA, Clifton KK, Ademuyiwa FO. Targeted treatment for high-risk early-stage triple-negative breast cancer: spotlight on pembrolizumab. Breast Cancer: Targets Ther. 2022;14:113–23. https://doi.org/10.2147/BCTT.S293597
DOI Google Scholar
6

Mediratta K, El-Sahli S, D'Costa V, D'Costa V, Wang L. Current progresses and challenges of immunotherapy in triple-negative breast cancer. Cancers. 2020;12(12):3529. https://doi.org/10.3390/cancers12123529
DOI Google Scholar
7

Ribeiro R, Carvalho MJ, Goncalves J, Moreira JN. Immunotherapy in triple-negative breast cancer: insights into tumor immune landscape and therapeutic opportunities. Front Mol Biosci. 2022;9:903065. https://doi.org/10.3389/fmolb.2022.903065
DOI Google Scholar
8

Schmid P, Rugo HS, Adams S, Schneeweiss A, Barrios CH, Iwata H, et al. Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2020;21(1):44–59. https://doi.org/10.1016/S1470-2045(19)30689-8
DOI Google Scholar
9

Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379(22):2108–21. https://doi.org/10.1056/NEJMoa1809615
DOI Google Scholar
10

Cortes J, Cescon DW, Rugo HS, Nowecki Z, Im SA, Yusof MM, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): a randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396(10265):1817–28. https://doi.org/10.1016/S0140-6736(20)32531-9
DOI Google Scholar
11

Cortes J, Rugo HS, Cescon DW, Im SA, Yusof MM, Gallardo C, et al. Pembrolizumab plus chemotherapy in advanced triple-negative breast cancer. N Engl J Med. 2022;387(3):217–26. https://doi.org/10.1056/NEJMoa2202809
DOI Google Scholar
12

Park S, Ock CY, Kim H, Pereira S, Park S, Ma M, et al. Artificial intelligence–powered spatial analysis of tumor-infiltrating lymphocytes as complementary biomarker for immune checkpoint inhibition in non–small-cell lung cancer. J Clin Oncol. 2022;40(17):1916–28. https://doi.org/10.1200/JCO.21.02010
DOI Google Scholar
13

Jardim DL, Goodman A, de Melo Gagliato D, Kurzrock R. The challenges of tumor mutational burden as an immunotherapy biomarker. Cancer Cell. 2021;39(2):154–73. https://doi.org/10.1016/j.ccell.2020.10.001
DOI Google Scholar
14

Kist De Ruijter L, van de Donk PP, Hooiveld-Noeken JS, Giesen D, Elias SG, Lub-de Hooge MN, et al. Whole-body CD8+ T cell visualization before and during cancer immunotherapy: a phase 1/2 trial. Nature Med. 2022;28(12):2601–10. https://doi.org/10.1038/s41591-022-02084-8
DOI Google Scholar
15

Schwartz LH, Litière S, de Vries E, Ford R, Gwyther S, Mandrekar S, et al. RECIST 1.1-Update and clarification: from the RECIST committee. Eur J Cancer. 2016;62:132–7. https://doi.org/10.1016/j.ejca.2016.03.081
DOI Google Scholar
16

Savas P, Salgado R, Denkert C, Sotiriou C, Darcy PK, Smyth MJ, et al. Clinical relevance of host immunity in breast cancer: from TILs to the clinic. Nat Rev Clin Oncol. 2016;13(4):228–41. https://doi.org/10.1038/nrclinonc.2015.215
DOI Google Scholar
17

Giovinazzo F, Bucaro A, Agnes S. Breast cancer liver metastasis: time to resection and criteria. Hepatobiliary Surg Nutr. 2022;11(5):749–51. https://doi.org/10.21037/hbsn-22-372
DOI Google Scholar
18

Yu J, Green MD, Li S, Sun Y, Journey SN, Choi JE, et al. Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination. Nature Med. 2021;27(1):152–64. https://doi.org/10.1038/s41591-020-1131-x
DOI Google Scholar
19

Chen L, Huang S, Liu Q, Kong X, Su Z, Zhu M, et al. PD-L1 protein expression is associated with good clinical outcomes and nomogram for prediction of disease free survival and overall survival in breast cancer patients received neoadjuvant chemotherapy. Front Immunol. 2022;13:849468. https://doi.org/10.3389/fimmu.2022.849468
DOI Google Scholar
20

Dai Y, Zhao W, Yue L, Dai X, Rong D, Wu F, et al. Perspectives on immunotherapy of metastatic colorectal cancer. Front Oncol. 2021;11:659964. https://doi.org/10.3389/fonc.2021.659964
DOI Google Scholar
21

Yazaki S, Salgado R, Shimoi T, Yoshida M, Shiino S, Kaneda T, et al. Impact of adjuvant chemotherapy and radiotherapy on tumour-infiltrating lymphocytes and PD-L1 expression in metastatic breast cancer. Br J Cancer. 2023;128(4):568–75. https://doi.org/10.1038/s41416-022-02072-2
DOI Google Scholar
22

Li J, Zhang S, Chen S, Yuan Y, Zuo M, Li T, et al. Lipid metabolism-related gene signature predicts prognosis and depicts tumor microenvironment immune landscape in gliomas. Front Immunol. 2023;14:1021678. https://doi.org/10.3389/fimmu.2023.1021678
DOI Google Scholar
23

Gataa I, Mezquita L, Rossoni C, Auclin E, Kossai M, Aboubakar F, et al. Tumour-infiltrating lymphocyte density is associated with favourable outcome in patients with advanced non-small cell lung cancer treated with immunotherapy. Eur J Cancer. 2021;145:221–9. https://doi.org/10.1016/j.ejca.2020.10.017
DOI Google Scholar
24

Liu S, Wu M, Wang F. Research progress in prognostic factors and biomarkers of ovarian cancer. J Cancer. 2021;12(13):3976–96. https://doi.org/10.7150/jca.47695
DOI Google Scholar
25

Long H, Hu CT, Prijatelj V, Weng CF. Antrodia cinnamomea is a potentially effective complementary medicine for adjuvant therapy against breast cancer with bone metastasis: a case report. Medicine. 2020;99(27):e20808. https://doi.org/10.1097/MD.0000000000020808
DOI Google Scholar
26

Lv Z, Yu Y, Luo Y, Lin S, Xiang X, Mao X, et al. Long-term survival outcomes of pediatric adrenal malignancies: an analysis with the upstaged SEER registry during 2000-2019. Front Endocrinol. 2022;13:977105. https://doi.org/10.3389/fendo.2022.977105
DOI Google Scholar
27

Wang Y, Jia A, Bi Y, Wang Y, Liu G. Metabolic regulation of myeloid-derived suppressor cell function in cancer. Cells. 2020;9(4):1011. https://doi.org/10.3390/cells9041011
DOI Google Scholar
28

Pérez-Tomás R, Pérez-Guillén I. Lactate in the tumor microenvironment: an essential molecule in cancer progression and treatment. Cancers. 2020;12(11):3244. https://doi.org/10.3390/cancers12113244
DOI Google Scholar
29

Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, et al. Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med. 2015;372(4):320–30. https://doi.org/10.1056/NEJMoa1412082
DOI Google Scholar
30

Robert C, Grob JJ, Stroyakovskiy D, Karaszewska B, Hauschild A, Levchenko E, et al. Five-year outcomes with dabrafenib plus trametinib in metastatic melanoma. N Engl J Med. 2019;381(7):626–36. https://doi.org/10.1056/NEJMoa1904059
DOI Google Scholar
31

Chen B, Dai D, Tang H, Chen X, Ai X, Huang X, et al. Pre-treatment serum alkaline phosphatase and lactate dehydrogenase as prognostic factors in triple negative breast cancer. J Cancer. 2016;7(15):2309–16. https://doi.org/10.7150/jca.16622
DOI Google Scholar
32

Russo A, Franchina T, Ricciardi GRR, Battaglia A, Scimone A, Berenato R, et al. Baseline neutrophilia, derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), and outcome in non-small cell lung cancer (NSCLC) treated with Nivolumab or Docetaxel. J Cell Physiol. 2018;233(10):6337–43. https://doi.org/10.1002/jcp.26609
DOI Google Scholar
33

Amer HT, Stein U, El Tayebi HM. The monocyte, a maestro in the tumor microenvironment (TME) of breast cancer. Cancers. 2022;14(21):5460. https://doi.org/10.3390/cancers14215460
DOI Google Scholar
34

Onagi H, Horimoto Y, Sakaguchi A, Ikarashi D, Yanagisawa N, Nakayama T, et al. High platelet-to-lymphocyte ratios in triple-negative breast cancer associates with immunosuppressive status of TILs. Breast Cancer Res. 2022;24(1):67. https://doi.org/10.1186/s13058-022-01563-7
DOI Google Scholar
35

Huszno J, Kolosza Z. Prognostic value of the neutrophil‑lymphocyte, platelet‑lymphocyte and monocyte‑lymphocyte ratio in breast cancer patients. Oncol Lett. 2019;18(6):6275–83. https://doi.org/10.3892/ol.2019.10966
DOI Google Scholar
36

Mezquita L, Preeshagul I, Auclin E, Saravia D, Hendriks L, Rizvi H, et al. Predicting immunotherapy outcomes under therapy in patients with advanced NSCLC using dNLR and its early dynamics. Eur J Cancer. 2021;151:211–20. https://doi.org/10.1016/j.ejca.2021.03.011
DOI Google Scholar
37

Ocaña A, Chacón JI, Calvo L, Antón A, Mansutti M, Albanell J, et al. Derived neutrophil-to-lymphocyte ratio predicts pathological complete response to neoadjuvant chemotherapy in breast cancer. Front Oncol. 2022;11:827625. https://doi.org/10.3389/fonc.2021.827625
DOI Google Scholar
38

Viñal D, Gutierrez-Sainz L, Martinez D, Garcia-Cuesta JA, Pedregosa J, Villamayor J, et al. Prognostic value of neutrophil-to-lymphocyte ratio in advanced cancer patients receiving immunotherapy. Clin Transl Oncol. 2021;23(6):1185–92. https://doi.org/10.1007/s12094-020-02509-1
DOI Google Scholar
Publication history
Copyright
Acknowledgements
Rights and permissions

Publication history

Received: 28 February 2023
Accepted: 16 March 2023
Published: 23 April 2023
Issue date: June 2023

Copyright

© 2023 The Authors. Tsinghua University Press.

Acknowledgements

ACKNOWLEDGMENTS

The authors thank everyone who contributed to this study.

Rights and permissions

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Return