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Immune checkpoint inhibitors combined with chemotherapy for the treatment of advanced pancreatic cancer patients

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Abstract

Immune checkpoint inhibitors (ICIs) represent a major breakthrough for cancer treatment. However, evidence regarding the use of ICIs in pancreatic cancer (PC) remained scarce. To assess the efficacy and safety of ICIs plus chemotherapy, patients with advanced PC were retrospectively recruited and were treated with either chemotherapy alone or chemotherapy plus ICIs. Patients previously treated with any agents targeting T-cell co-stimulation or checkpoint pathways were excluded. The primary outcome was overall survival (OS). The secondary outcomes were progression-free survival (PFS), overall response rate (ORR) and safety. In total, 58 patients were included (combination, n = 22; chemotherapy, n = 36). The combination group showed a significantly longer OS than the chemotherapy group [median, 18.1 vs 6.1 months, hazard ratio (HR) 0.46 (0.23–0.90), P = 0.021]. The median PFSs were 3.2 months in the combination group and 2.0 months in the chemotherapy group [HR 0.57 (0.32–0.99), P = 0.041]. The combination group and the chemotherapy group had similar ORRs (18.2% vs 19.4%, P = 0.906). All patients who achieved a partial response received a doublet chemotherapy regimen regardless of co-treatment with ICIs. Grade 3 or higher adverse events occurred in 31.8% of the patients in the combination group and in 16.9% of those receiving chemotherapy. Although the incidence of serious treatment-related adverse events was higher in the combination group than in the chemotherapy group, the difference was not significant (P = 0.183). Our findings suggest that the combination of ICIs with chemotherapy is both effective and tolerable for advanced PC. ICIs combined with a doublet chemotherapy regimen might be a preferable choice.

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Abbreviations

ASCO:

American Society of Clinical Oncology

ASCO-GI:

American Society of Clinical Oncology-gastrointestinal cancer

CR:

Complete response

DCR:

Disease control rate

ECOG:

Eastern Cooperative Oncology Group

FOLFIRINOX:

Fluorouracil/leucovorin plus irinotecan plus oxaliplatin

GEST:

Gemcitabine and S-1 Trial

HR:

Hazard ratio

ICI:

Immune checkpoint inhibitor

dMMR:

Mismatch repair deficient

mOS:

Median overall survival

mPFS:

Median progression-free survival

MSI-H:

Microsatellite instability-high

ORR:

Overall response rate

PC:

Pancreatic cancer

PR:

Partial response

PS:

Performance status

SD:

Stable disease

TRAE:

Treatment-related adverse event

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Acknowledgements

We thank the patients and their families.

Funding

This work was funded by the National Natural Science Foundation of China [81402552 to Yi Hu, 81672996 to Yi Hu].

Author information

Author notes

  1. Junxun Ma and Danyang Sun are co-first authors.

Authors and Affiliations

  1. Department of Medical Oncology, Chinese People’s Liberation Army General Hospital, 28 Fuxing Road, Haidian, Beijing, 100853, People’s Republic of China

    Junxun Ma, Jinliang Wang, Chun Han, Yuanyu Qian, Guangying Chen, Xiaoyan Li, Juan Zhang, Pengfei Cui, Wushuang Du, Zhaozhen Wu, Shixue Chen, Xuan Zheng, Zhichao Yue & Yi Hu

  2. Intensive Care Unit, West Ward, China-Japan Friendship Hospital, Beijing, People’s Republic of China

    Danyang Sun

  3. The Medical Department, 3D Medicines Inc., 158 Xinjunhuan Road, Minhang, Shanghai, 201114, People’s Republic of China

    Jia Song, Chan Gao & Shangli Cai

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  1. Junxun Ma
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Contributions

Conception and design: JXM, DYS, SLC and YH. Protocol writing: JXM, DYS, JS, SLC and YH. Data collection: CH, JLW, YYQ, GYC, XYL, PFC, JZ, WSD, SXC, ZZW, XZ and ZCY. Data analysis: JS, JXM and CG. Manuscript writing: JS, JXM, DYS and JLW. Manuscript revisions: CG, YH and SLC. All authors contributed to writing and reviewing the manuscript and approved the final version of the manuscript.

Corresponding authors

Correspondence to Shangli Cai or Yi Hu.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval and ethical standards

The study was approved by the institutional review board of the People’s Liberation Army General Hospital, Beijing, China (approval number: S2018-144-02). This clinical study was conducted in accordance with the Helsinki declaration and its later amendments.

Informed consent

Because of the retrospective nature of the study, informed consent was waived by the People’s Liberation Army General Hospital, Beijing. This paper does not contain any individual person’s data in any form.

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Parts of the data have been published as an abstract at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting which was held during May 31–June 4, in Chicago, IL, USA [1].

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Ma, J., Sun, D., Wang, J. et al. Immune checkpoint inhibitors combined with chemotherapy for the treatment of advanced pancreatic cancer patients. Cancer Immunol Immunother 69, 365–372 (2020). https://doi.org/10.1007/s00262-019-02452-3

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