We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine

Hyperprogressive disease in hepatocellular carcinoma with immune checkpoint inhibitor use: a case series

    Daniel Jiahao Wong

    Faculty of Medicine, University of New South Wales, Sydney, New South Wales, 2052, Australia

    ,
    Joycelyn Lee

    Department of Medical Oncology, National Cancer Centre, Singapore,169610, Singapore

    ,
    Su Pin Choo

    Department of Medical Oncology, National Cancer Centre, Singapore,169610, Singapore

    ,
    Choon Hua Thng

    Department of Oncologic Imaging, National Cancer Centre, Singapore, 169610, Singapore

    &
    Tiffany Hennedige

    *Author for correspondence: Tel.: +65 6436 8000;

    E-mail Address: hennedige.tiffany.priyanthi@singhealth.com.sg

    Department of Oncologic Imaging, National Cancer Centre, Singapore, 169610, Singapore

    Published Online:https://doi.org/10.2217/imt-2018-0126

    Immune checkpoint inhibitors (ICIs) have demonstrated promising results in a variety of advanced cancer types. The phenomenon of hyperprogressive disease (HPD) has only been documented in recent years, however, there have been no reports of HPD in hepatocellular carcinoma. We present a case series of six patients with advanced hepatocellular carcinoma treated with ICIs who demonstrated rapid radiological progression, this was confirmed by comparing tumor growth rates before and during treatment with HPD defined as tumor growth rateratio ≥2. Although ICIs have demonstrated profound efficacy in advanced cancer, they might also be responsible for HPD in a small subset of patients. The ability to predict treatment response to ICI is thus of importance in protecting patients from the deleterious effects of HPD.

    References

    • 1 Bosetti C, Turati F, La Vecchia C. Hepatocellular carcinoma epidemiology. Best Pract. Res. Clin. Gastroenterol. 28(5), 753–770 (2014).
    • 2 Llovet JM, Ricci S, Mazzaferro V et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 359(4), 378–390 (2008).
    • 3 Cheng AL, Kang YK, Chen ZD et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a Phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 10(1), 25–34 (2009).
    • 4 Garon EB, Rizvi NA, Hui R et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N. Engl. J. Med. 372(21), 2018–2028 (2015).
    • 5 Weber JS, D'angelo SP, Minor D et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, Phase 3 trial. Lancet Oncol. 16(4), 375–384 (2015).
    • 6 Antonia SJ, Villegas A, Daniel D et al. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N. Engl J. Med. 377(20), 1919–1929 (2017).
    • 7 El-Khoueiry AB, Sangro B, Yau T et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, Phase 1/2 dose escalation and expansion trial. Lancet 389(10088), 2492–2502 (2017).
    • 8 Bruix J, Qin S, Merle P et al. Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, Phase 3 trial. Lancet 389(10064), 56–66 (2017).
    • 9 Kudo M. Immune checkpoint inhibition in hepatocellular carcinoma: basics and ongoing clinical trials. Oncology 92(Suppl. 1), 50–62 (2017).
    • 10 Wolchok JD, Hoos A, O'day S et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin. Cancer Res. doi:10.1158/1078-0432.CCR-09-1624 (2009).
    • 11 Hodi FS, Hwu WJ, Kefford R et al. Evaluation of immune-related response criteria and RECIST v1.1 in patients with advanced melanoma treated with pembrolizumab. J. Clin. Oncol. 34(13), 1510–1517 (2016).
    • 12 Nishino M, Giobbie-Hurder A, Manos MP et al. Immune-related tumor response dynamics in melanoma patients treated with pembrolizumab: identifying markers for clinical outcome and treatment decisions. Clin. Cancer Res. 23(16), 4671 (2017).
    • 13 Wang Q, Gao J, Wu X. Pseudoprogression and hyperprogression after checkpoint blockade. Int. J. Immunopharmacol. 58, 125–135 (2018).
    • 14 Solinas C, Porcu M, Hlavata Z et al. Critical features and challenges associated with imaging in patients undergoing cancer immunotherapy. Crit. Rev. Oncol. Hematol. 120, 13–21 (2017).
    • 15 Seymour L, Bogaerts J, Perrone A et al. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 18(3), e143–e152 (2017).
    • 16 Chubachi S, Yasuda H, Irie H et al. A case of non-small cell lung cancer with possible ‘disease flare’ on nivolumab treatment. Case Rep. Oncol. Med. 2016, 1075641 (2016).
    • 17 Denaro N. Hyperprogression after immunotherapy in HNC: literature review and our experience. Int J Radiol Radiat Oncol. 4(1), 001–002 (2018).
    • 18 Faure M, Rochigneux P, Olive D, Taix S, Brenot-Rossi I, Gilabert M. Hyperprogressive disease in anorectal melanoma treated by PD-1 inhibitors. Front. Immunol. 9, 797 (2018). DOI:10.3389/fimmu.2018.00797.
    • 19 Occhipinti M, Falcone R, Onesti CE, Marchetti P. Hyperprogressive disease and early hypereosinophilia after anti-PD-1 treatment: a case report. Drug Saf. Case Rep. 5(1), (12), (2018). DOI: 10.1007/s40800-018-0078-z.
    • 20 Shinozaki T, Iwami E, Ikemura S et al. A case of pulmonary adenocarcinoma showing rapid progression of peritoneal dissemination after immune checkpoint inhibitor therapy. BMC Cancer 18(1), (620), (2018). 10.1186/s12885-018-4549-5.
    • 21 Yoshida T, Furuta H, Hida T. Risk of tumor flare after nivolumab treatment in patients with irradiated field recurrence. Med. Oncol. 34(3), 34 (2017).
    • 22 Champiat S, Dercle L, Ammari S et al. Hyperprogressive disease is a new pattern of progression in cancer patients treated by anti-PD-1/PD-L1. Clin. Cancer Res. 23(8), 1920–1928 (2017).
    • 23 Saada-Bouzid E, Defaucheux C, Karabajakian A et al. Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma. Ann. Oncol. 28(7), 1605–1611 (2017).
    • 24 Kato S, Goodman A, Walavalkar V, Barkauskas DA, Sharabi A, Kurzrock R. Hyperprogressors after immunotherapy: analysis of genomic alterations associated with accelerated growth rate. Clin. Cancer Res. 23(15), 4242–4250 (2017).
    • 25 Weiss GJ, Beck J, Braun DP et al. Tumor cell-free DNA copy number instability predicts therapeutic response to immunotherapy. Clin. Cancer Res. 23(17), 5074–5081 (2017).
    • 26 Ogata T, Satake H, Ogata M, Hatachi Y, Yasui H. Hyperprogressive disease in the irradiation field after a single dose of nivolumab for gastric cancer: a case report. Case Rep. Oncol. 11(1), 143–150 (2018).
    • 27 Yu SJ. A concise review of updated guidelines regarding the management of hepatocellular carcinoma around the world: 2010–2016. Clin. Mol. Hepatol. 22(1), 7–17 (2016).
    • 28 Hepatobiliary Cancers. NCCN Clinical Practice Guidelines in Oncology. (NCCN Guidelines) (5 June 2018), (2018).
    • 29 Sangro B, Park JW, Cruz CMD et al. A randomized, multicenter, Phase 3 study of nivolumab vs sorafenib as first-line treatment in patients with advanced hepatocellular carcinoma: CheckMate-459. J. Clin. Oncol. 34(15 suppl 1), TPS4147 (2016).
    • 30 Peng W, Liu C, Xu C et al. PD-1 blockade enhances T cell migration to tumors by elevating IFN-γ inducible chemokines. Cancer Res. doi:10.1158/0008-5472.Can-12-1187 (2012).
    • 31 Waight JD, Netherby C, Hensen ML et al. Myeloid-derived suppressor cell development is regulated by a STAT/IRF-8 axis. J. Clin. Invest. 123(10), 4464–4478 (2013).
    • 32 Schindler C, Levy DE, Decker T. JAK-STAT signaling: from interferons to cytokines. J. Biol. Chem. 282(28), 20059–20063 (2007).
    • 33 Vassilev LT, Vu BT, Graves B et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303(5659), 844–848 (2004).
    • 34 Sakai S, Kauffman KD, Sallin MA et al. CD4 T cell-derived IFN-γ plays a minimal role in control of pulmonary mycobacterium tuberculosis infection and must be actively repressed by PD-1 to prevent lethal disease. PLoS Pathog. 12(5), e1005667 (2016).
    • 35 Barker HE, Paget JT, Khan AA, Harrington KJ. The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence. Nat. Rev. Cancer 15(7), 409 (2015).
    • 36 Koyama S, Akbay EA, Li YY et al. Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints. Nat. Commun. 7, 10501 (2016).
    • 37 Kleffel S, Posch C, Barthel SR et al. Melanoma cell-intrinsic PD-1 receptor functions promote tumor growth. Cell 162(6), 1242–1256 (2015).