New Systemic Treatment Options for Hepatobiliary Cancers

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Robin Kate Kelley
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Multiple systemic therapy options now exist for unresectable and metastatic hepatocellular carcinoma (HCC). Atezolizumab + bevacizumab is the preferred first-line regimen, and although many second-line treatment options have recently been added to the NCCN Guidelines, none have been studied after atezolizumab + bevacizumab (all post-sorafenib), and therefore optimal sequence has yet to be established. Multiple new combination regimens with immune checkpoint inhibitors are also being studied in advanced-stage HCC. In biliary tract cancer (BTC), gemcitabine + cisplatin remains the preferred first-line regimen. FOLFOX is the preferred regimen in the second line. Multiple targeted therapy options are now available in second-line BTC for patients with tumors harboring specific mutations, and these therapeutic targets may guide future treatment sequence and combinations for BTCs.

Disclosures: Dr. Kelley has disclosed serving as a scientific advisor for Exact Sciences, Genentech/Roche, and Merck; and receiving consulting fees from Gilead, Genentech/Roche, and Ipsen.

Correspondence: Robin Kate Kelley, MD, UCSF Helen Diller Family Comprehensive Cancer Center, 550 16th Street, Box 3211, San Francisco, CA 94143. Email: katie.kelley@ucsf.edu
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  • 1.

    Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394424.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Saha SK, Zhu AX, Fuchs CS, et al. Forty-year trends in cholangiocarcinoma incidence in the U.S.: intrahepatic disease on the rise. Oncologist 2016;21:594599.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378390.

  • 4.

    Kudo M, Finn RS, Qin S, Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet 2018;391:11631173.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Cancer Genome Atlas Research Network. Comprehensive and integrative genomic characterization of hepatocellular carcinoma. Cell 2017;169:13271341.e23.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    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 2017;389:24922502.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Yau T, Park JW, Finn RS, et al. CheckMate 459: a randomized, multi-center phase 3 study of nivolumab vs sorafenib as first-line treatment in patients with advanced hepatocellular carcinoma. Ann Oncol 2019;30(Suppl 5):v851934.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 2020;382:18941905.

  • 9.

    Finn RS, Qin S, Ikeda M, et al. IMbrave150: updated overall survival data from a global, randomized, open-label phase III study of atezolizumab + bevacizumab versus sorafenib in patients with unresectable hepatocellular carcinoma [abstract]. Presented at the 2021 Gastrointestinal Cancers Symposium; January 15–17, 2021. Abstract 267.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    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 2017;389:5666.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Abou-Alfa GK, Meyer T, Cheng A, et al. Cabozantinib in patients with advanced and progressing hepatocellular carcinoma. N Engl J Med 2018;379:5463.

  • 12.

    Zhu AX, Kang Y, Yen C, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2019;20:282296.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    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 2017;389:24922502.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Finn RS, Ryoo B, Merle P, et al. Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: a randomized, double-blind, phase III trial. J Clin Oncol 2020;38:193202.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Yau T, Kang Y, Kim T, et al. Efficacy and safety of nivolumab plus ipilimumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib: the CheckMate 040 randomized clinical trial. JAMA Oncol 2020;6:e204564.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Valle J, Wasan H, Palmer DH, Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 2010;362:12731281.

  • 17.

    Lamarca A, Palmer DH, Wasan HS, et al. Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial. Lancet Oncol 2021;22:690701.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Le DT, Durham JN, Smith KN, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 2017;357:409413.

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