Skip to main content

Advertisement

SpringerLink
Log in

Efficacy of pembrolizumab in microsatellite instability-high locally advanced cholangiocarcinoma: a case report

  • Case Report
  • Published:
Clinical Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Cholangiocarcinoma is a biliary malignant tumor which can arise at any point of biliary tree. Surgical resection is the only curative treatment and chemotherapy is used for unresectable cases, but its prognosis is poor compared with other types of cancer. Recently, pembrolizumab (PEM), an anti-programmed cell death protein 1 (PD-1) antibody, has become available for microsatellite instability (MSI)-high advanced cancers. Here, we report the use of PEM for MSI-high locally advanced cholangiocarcinoma. A 57-year-old man presented to our department with jaundice. Contrast-enhanced computed tomography showed a solitary 28-mm-diameter tumor deep in the anterior segment of the liver. Endoscopic retrograde cholangiopancreatography and intraductal ultrasonography showed narrowing of the common bile duct and absence of contrast in the right hepatic duct, and tumor invaded from hilar region of liver into left hepatic duct. We diagnosed this as double primary cancers, locally advanced intrahepatic and distal cholangiocarcinomas. The patient began gemcitabine in combination with cisplatin therapy as first-line treatment and gemcitabine in combination with S-1 therapy as second-line treatment. However, the tumor gradually grew (maximum 69 mm), intrahepatic metastasis appeared, and tumor marker increased. Because MSI-high was confirmed not only by biopsy specimens but also by liquid biopsy, the patient began PEM (200 mg per every 3 weeks). After 15 cycles of PEM were administered over about 10 months, size of tumor was reduced and tumor marker dramatically decreased. We experienced the rare case which PEM has been successfully used for MSI-high double primary cancers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

PD-1:

Anti-programmed cell death protein 1

CECT:

Contrast-enhanced computed tomography

ERCP:

Endoscopic retrograde cholangiopancreatography

ICIs:

Immune therapy with checkpoint inhibitors

IDUS:

Intraductal ultrasonography

dMMR:

Mismatch repair-deficient

MSI:

Microsatellite instability

ORR:

Objective response rate

OS:

Overall survival

PFS:

Progression-free survival

PEM:

Pembrolizumab

RECIST:

Response evaluation criteria in solid tumors

References

  1. Rizvi S, Gores GJ. Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology. 2013;145:1215–29.

    Article  CAS  Google Scholar 

  2. Saha SK, Zhu AX, Fuchs CS, et al. Forty-year trends in cholangiocarcinoma incidence in the US: intrahepatic disease on the rise. Oncologist. 2016;21:594–9.

    Article  Google Scholar 

  3. Khan SA, Taylor-Robinson SD, Toledano MB, et al. Changing international trends in mortality rates for liver, biliary and pancreatic tumors. J Hepatol. 2002;37:806–13.

    Article  Google Scholar 

  4. Matsumoto T, Itoh S, Yoshizumi T, et al. C -reactive protein: albumin ratio in patients with resectable intrahepatic cholangiocarcinoma. BJS Open. 2020;4:1146–52.

    Article  Google Scholar 

  5. Strijker M, Belkouz A, van der Geest LG, et al. Treatment and survival of resected and unresected distal cholangiocarcinoma: a nationwide study. Acta Oncol. 2019;58:1048–55.

    Article  Google Scholar 

  6. Lindner P, Rizell M, Hafstrom L. The impact of changed strategies for patients with cholangiocarcinoma in this millenium. HPB Surg. 2015;2015:736049.

    Article  Google Scholar 

  7. Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362:1273–81.

    Article  CAS  Google Scholar 

  8. Morizane C, Okusada T, Mizusawa J, et al. Combination gemcitabine plus S-1 versus gemcitabine plus cisplatin for advanced/recurrent biliary tract cancer: the FUGA-BT (JCOG1113) randomized phase III clinical trial. Ann Oncol. 2019;30:1950–8.

    Article  CAS  Google Scholar 

  9. Kim HD, Park SH. Immunological and clinical implications of immune checkpoint blockade in human cancer. Arch Pharm Res. 2019;42:567–81.

    Article  CAS  Google Scholar 

  10. Francisco LM, Salinas VH, Brown KE, et al. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med. 2009;206:3015–29.

    Article  CAS  Google Scholar 

  11. Marabelle A, Le DT, Ascierto PA, et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/ mismatch repair–deficient cancer: Results from the phase II KEYNOTE-158 study. J Clin Oncol. 2020;38:1–10.

    Article  CAS  Google Scholar 

  12. Naganuma A, Sakuda T, Murakami T, et al. Microsatellite instability-high intrahepatic cholangiocarcinoma with portal vein tumor thrombosis successfully treated with pembrolizumab. Intern Med. 2020;59:2261–7.

    Article  Google Scholar 

  13. Nakamura M, Ueno M, Hayami M, et al. Effective response of intrahepatic cholangiocarcinoma to pembrolizumab: a case report. Anticancer Res. 2020;40:4123–9.

    Article  Google Scholar 

  14. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumors: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.

    Article  CAS  Google Scholar 

  15. Willis J, Lefterova MI, Artyomenko A, et al. Validation of microsatellite instability detection using a comprehensive plasma-based genotyping panel. Clin Cancer Res. 2019;25:7035–45.

    Article  CAS  Google Scholar 

  16. Odegaard JI, Vincent JJ, Mortimer S, et al. Validation of a plasma-based comprehensive cancer genotyping assay utilizing orthogonal tissue- and plasma-based methodologies. Clin Cancer Res. 2018;24:3539–49.

    Article  CAS  Google Scholar 

  17. Chen DS, Mellman I. Oncology meets immunology: the cancer- immunity cycle. Immunity. 2013;3(9):1–10.

    Article  CAS  Google Scholar 

  18. Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Oncol. 2015;33:1974–82.

    Article  CAS  Google Scholar 

  19. Yarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to PD-1 Inhibition. New Engl J Med. 2017;377:2500–1.

    Article  Google Scholar 

  20. Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017;357:409–13.

    Article  CAS  Google Scholar 

  21. Lee V, Murphy A, Le DT, et al. Mismatch repair deficiency and response to immune checkpoint blockade. Oncologist. 2016;21:1200–11.

    Article  CAS  Google Scholar 

  22. Akagi K, Oki E, Taniguchi H, et al. The real-world data on microsatellite instability status in various unresectable or metastatic solid tumors. Cancer Sci. 2021;112:1105–13.

    Article  CAS  Google Scholar 

  23. Lynch HT, Snyder CL, Shaw TG, et al. Milestones of Lynch syndrome: 1895–2015. Nat Rev Cancer. 2015;15:181–94.

    Article  CAS  Google Scholar 

  24. Vasen HF, Watson P, Mecklin JP, et al. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative Group on HNPCC. Gastroenterology. 1999;116:1453–6.

    Article  CAS  Google Scholar 

  25. Nakamura Y, Taniguchi H, Ikeda M, et al. Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer: SCRUM-Japan GI-SCREEN and GOZILA studies. Nat Med. 2020;26:1859–64.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr. Trish Reynolds, MBBS, FRACP, from Edanz Group (https://en-author-services.edanz.com/ac) for editing a draft of this manuscript.

Author information

Authors and Affiliations

  1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Katsuya Toshida, Shinji Itoh, Tomoharu Yoshizumi, Tomonari Shimagaki, Huanlin Wang, Takeshi Kurihara, Takeo Toshima, Yoshihiro Nagao, Noboru Harada, Eiji Oki & Masaki Mori

  2. Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan

    Yoshiaki Nakamura & Takayuki Yoshino

Authors
  1. Katsuya Toshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shinji Itoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tomoharu Yoshizumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tomonari Shimagaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Huanlin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takeshi Kurihara
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Takeo Toshima
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yoshihiro Nagao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Noboru Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Eiji Oki
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Yoshiaki Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Takayuki Yoshino
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Masaki Mori
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shinji Itoh.

Ethics declarations

Conflict of interest

Katsuya Toshida, Shinji Itoh, Tomoharu Yoshizumi, Tomonari Shimagaki, Huanlin Wang, Takeshi Kurihara, Takeo Toshima, Yoshihiro Nagao, Noboru Harada, Eiji Oki, Yoshiaki Nakamura, Takayuki Yoshino and Masaki Mori declare that they have no conflict of interest.

Human rights

All procedures followed have been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed consent

Informed consent was obtained from all patients for being included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Toshida, K., Itoh, S., Yoshizumi, T. et al. Efficacy of pembrolizumab in microsatellite instability-high locally advanced cholangiocarcinoma: a case report. Clin J Gastroenterol 14, 1459–1463 (2021). https://doi.org/10.1007/s12328-021-01458-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12328-021-01458-8

Keywords

Search

Navigation