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The real-world data of immune-checkpoint inhibitor combination therapy for unresectable or metastatic esophageal cancer: a multi-institutional cohort study

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Abstract

Background

The real-world efficacy, feasibility, and prognostic factors of immune-checkpoint inhibitor combination therapy for unresectable or metastatic esophageal cancer are not fully established.

Methods

This multi-institutional retrospective cohort study evaluated 71 consecutive patients treated with immune-checkpoint inhibitor combination therapy for esophageal cancer between March 2021 and December 2022. We assessed tumor response, safety, and long-term survival.

Results

In patients with measurable lesions, the response rate was 58%, and the disease control rate for all enrolled patients was 80%. Five patients (7.0%) underwent successful conversion surgery. Grade 3 or higher immune-related adverse events occurred in 13% of patients, and one patient (1.4%) died due to cholangitis. Median progression-free survival was 9.7 (95% confidence interval: 6.5–not reached). C-reactive protein levels and performance status were identified as significant predictors of progression-free survival through Cox proportional hazards analysis.

Conclusions

Immune-checkpoint inhibitor combination therapy for esophageal cancer demonstrated comparable tumor response, safety, and long-term survival to previous randomized clinical trials. Patients with good performance status and low C-reactive protein levels may be suitable candidates for this treatment.

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Data availability

The evaluation data set analyzed in the current study is not available publicly. However, the data are available from the corresponding author on request.

References

  1. Sung H, Ferlay J, Siegel RL et al (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71:209–249

    Article  PubMed  Google Scholar 

  2. Lee SJ, Kim S, Kim M et al (2015) Capecitabine in combination with either cisplatin or weekly paclitaxel as a first-line treatment for metastatic esophageal squamous cell carcinoma: A randomized phase II study. BMC Cancer 14(15):693

    Article  Google Scholar 

  3. Bleiberg H, Conroy T, Paillot B et al (1997) Randomised Phase II Study of Cisplatin and 5Fluorouracil (5FU) Versus Cisplatin Alone in Advanced Squamous Cell Oesophageal Cancer. Europ J Cancer 33:1216–1220

    Article  CAS  Google Scholar 

  4. Sun JM, Shen L, Shah MA et al (2021) Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet 28(398):759–771

    Article  Google Scholar 

  5. Doki Y, Ajani JA, Kato K et al (2022) Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma. N Engl J Med 386:449–462

    Article  CAS  PubMed  Google Scholar 

  6. Shah MA, Kennedy EB, Ashley A-RE et al (2023) Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer: ASCO Guideline. J Clin Oncol 41:1470–1491

    Article  CAS  PubMed  Google Scholar 

  7. Hayashi H, Nakagawa K (2020) Combination therapy with PD-1 or PD-L1 inhibitors for cancer. Int J Clin Oncol 25:818–830

    Article  CAS  PubMed  Google Scholar 

  8. Chamoto K, Hatae R, Honjo T (2020) Current issues and perspectives in PD-1 blockade cancer immunotherapy. Int J Clin Oncol 25:790–800

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kelley RK, Ueno M, Yoo C et al (2023) Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 401:1853–1865

    Article  PubMed  Google Scholar 

  10. Oaknin A, Gladieff L, Martínez-García J et al (2023) Atezolizumab plus bevacizumab and chemotherapy for metastatic, persistent, or recurrent cervical cancer (BEATcc): a randomised, open-label, phase 3 trial. Lancet S0140–6736(23):02405–02414

    Google Scholar 

  11. Satake S, Arigami T, Matsushita D et al (2023) Clinical Significance of Eligibility Criteria Determined by the SPIRITS Trial in Patients with Advanced Gastric Cancer. Oncology 101:12–21

    Article  CAS  PubMed  Google Scholar 

  12. Aoki Y, Kawazoe A, Kubota Y et al (2022) Characteristics and clinical outcomes of patients with advanced gastric or gastroesophageal cancer treated in and out of randomized clinical trials of first-line immune checkpoint inhibitors. Int J Clin Oncol 27:1413–1420

    Article  PubMed  Google Scholar 

  13. Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) RECIST version 1.1 JCOG ver1.0. Eur J Cancer 45(2):228–247

    Article  CAS  PubMed  Google Scholar 

  14. Common Terminology Criteria for Adverse Events v5.0: Institute NC. https://evs.nci.nih.gov/ftp1/CTCAE/About.html. Accessed Sep 2023

  15. Zhang L, Ma W, Qiu Z et al (2023) Prognostic nutritional index as a prognostic biomarker for gastrointestinal cancer patients treated with immune checkpoint inhibitors. Front Immunol 14:1219929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kojima T, Hara H, Tsuji A et al (2022) First-line pembrolizumab + chemotherapy in Japanese patients with advanced/metastatic esophageal cancer from KEYNOTE-590. Esophagus 19:683–692

    Article  PubMed  PubMed Central  Google Scholar 

  17. Sato S, Oshima Y, Matsumoto Y et al (2021) The new prognostic score for unresectable or recurrent gastric cancer treated with nivolumab: A multi-institutional cohort study. Ann Gastroenterol Surg 5:794–803

    Article  PubMed  PubMed Central  Google Scholar 

  18. Gao Y, Zhang Z, Li Y et al (2022) Pretreatment Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker in Unresectable or Metastatic Esophageal Cancer Patients With Anti-PD-1 Therapy. Front Oncol 3(12):834564

    Article  Google Scholar 

  19. Chang L, Cheng Q, Ma Y et al (2022) Prognostic Effect of the Controlling Nutritional Status Score in Patients With Esophageal Cancer Treated With Immune Checkpoint Inhibitor. J Immunother 45(9):415–422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Carroll TM, Chadwick JA, Owen RP et al (2023) Tumor monocyte content predicts immunochemotherapy outcomes in esophageal adenocarcinoma. Cancer Cell 41:1222–1241

    Article  CAS  PubMed  Google Scholar 

  21. Yoshida K, Yasufuku I, Terashima M et al (2022) International Retrospective Cohort Study of Conversion Therapy for Stage IV Gastric Cancer 1 (CONVO-GC-1). Ann Gastroenterol Surg 6:227–240

    Article  PubMed  Google Scholar 

  22. Sato S, Kunisaki C, Tanaka Y et al (2019) Curative-Intent Surgery for Stage IV Advanced Gastric Cancer: Who Can Undergo Surgery and What Are the Prognostic Factors for Long-Term Survival? Ann Surg Oncol 26:4452–4463

    Article  PubMed  Google Scholar 

  23. Matsuda S, Tsushima T, Kato K et al (2022) Defining conversion therapy for esophageal squamous cell carcinoma. Ann Gastroenterol Surg 7(1):7–9

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was supported by investigators at 8 hospitals (Toho University Omori Medical Center, Jichi Medical University Hospital, Fukushima medical University, Jikei University Hospital, Yokohama City University Hospital, Teikyo University School of Medicine, Yokohama City University Medical Center,). We thank all investigators at these institutions.

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Authors and Affiliations

  1. Department of Surgery, Yokohama City University Gastroenterological Center, Yokohama, Japan

    Sho Sato & Chikara Kunisaki

  2. Department of Surgery, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-Ku, Tokyo, 143-8541, Japan

    Takashi Ssuzuki & Hideaki Shimada

  3. Department of Clinical Oncology, Jichi Medical University Hospital, Tochigi, Japan

    Takashi Chinen & Hironori Yamaguchi

  4. Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan

    Yusuke Suzuki & Nobukazu Hokamura

  5. Department of Gastrointestinal Tract Surgery, Fukushima Medical University, Fukushima, Japan

    Zenichiro Saze & Koji Kono

  6. Department of Surgery, Jikei University School of Medicine, Tokyo, Japan

    Keita Takahashi & Fumiaki Yano

  7. Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan

    Takashi Kosaka & Itaru Endo

  8. Department of Clinical Oncology, Yokohama City University School of Medicine, Yokohama, Japan

    Yasushi Ichikawa

  9. Department of Gastroenterological Surgery, Saitama Medical University International Medical Center, Saitama, Japan

    Yutaka Miyawaki & Hiroshi Sato

Authors
  1. Sho Sato
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  2. Takashi Ssuzuki
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  3. Takashi Chinen
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  4. Hironori Yamaguchi
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  5. Yusuke Suzuki
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  6. Nobukazu Hokamura
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  7. Zenichiro Saze
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  8. Koji Kono
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  9. Keita Takahashi
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  10. Fumiaki Yano
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  11. Chikara Kunisaki
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  12. Takashi Kosaka
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  13. Itaru Endo
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  14. Yasushi Ichikawa
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  15. Yutaka Miyawaki
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  16. Hiroshi Sato
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  17. Hideaki Shimada
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Contributions

Author S.S and H.S contributed to the study conception, design, data analysis, and interpretation. Data collection was performed by author T.S, T.C, S.H, Y.S, Z.S, K.T, T.K, and Y.M. The first draft of the manuscript was written by author S.S and H.S. All authors commented on previous versions of the manuscript and approved the final manuscript.

Corresponding author

Correspondence to Hideaki Shimada.

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Conflict of interest

Authors S.S, T.K, K.K, H.Y, H.S, Y.M, Y.I, Y.S, S.H, and H.S received lecture fee from Ono pharmaceutical co., ltd. Authors S.S and S.H received lecture fee from Bristol Myers Squibb co. Authors S.S, K.K, H.Y, and H.S received lecture fee from Taiho pharmaceutical co. ltd. Authors S.S, K.K, H.Y, H.S, Y.M, S.H, and H.S received lecture fee from MSD co. ltd. Authors S.S and K.K received lecture fee from DAIICHI SANKYO co. ltd. Authors K.K and H.Y received lecture fee from Chugai pharmaceutical co. Authors Y.I, H.Y, and K.K received lecture fee from Takeda pharmaceutical co., ltd. Author H.Y received lecture fee from Yakult Honsha co., ltd. Authors I.E and H.S received research grant from Ono pharmaceutical co., ltd. Authors H.Y, C.K, and H.S received research grant from Taiho pharmaceutical co. ltd. Authors H.Y, C.K, I.E, and Y.I received research grant from Chugai pharmaceutical co. Authors Y.S and C.K received research grant from Yakult Honsha co., ltd. Author Y.I received research grant from Takeda pharmaceutical co. ltd and Shionogi pharmaceutical co. ltd. Author I.E received research grant from Asahi Kasei Pharma corporation.

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Sato, S., Ssuzuki, T., Chinen, T. et al. The real-world data of immune-checkpoint inhibitor combination therapy for unresectable or metastatic esophageal cancer: a multi-institutional cohort study. Int J Clin Oncol (2024). https://doi.org/10.1007/s10147-024-02532-0

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  • DOI: https://doi.org/10.1007/s10147-024-02532-0

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