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Original Paper

Sorafenib-Regorafenib Sequential Therapy in Advanced Hepatocellular Carcinoma: A Single-Institute Experience

Ueshima K. · Nishida N. · Kudo M.

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Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan

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Dig Dis 2017;35:611-617

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: October 17, 2017
Issue release date: October 2017

Number of Print Pages: 7
Number of Figures: 3
Number of Tables: 3

ISSN: 0257-2753 (Print)
eISSN: 1421-9875 (Online)

For additional information: https://www.karger.com/DDI

Abstract

Objectives: Previously, no therapeutic agent has been known to improve the overall survival compared with placebo in patients with hepatocellular carcinoma (HCC), who have progressed after sorafenib. In this patient population, regorafenib was first demonstrated to confer a survival benefit in the RESORCE trial, and subsequently it was approved as a second-line treatment for patients with advanced HCC. An open-label expanded access program (EAP) of regorafenib was implemented for compassionate use. We investigated the efficacy and safety of regorafenib based on our experience of the RESORCE trial and the EAP. Methods: Data from 5 patients from the RESORCE trial and 6 from the EAP were analyzed retrospectively. All patients had tolerated prior sorafenib and were progressing during sorafenib treatment. Results: The median progression-free survival was 9.2 months (95% CI 2.3-16.1). One patient achieved a partial response and 7 achieved stable disease. The objective response rate was 9.1%, and the disease control rate was 72.7%. No treatment-associated mortalities were observed. Grade 3 hypophosphatemia was observed in 2 patients, grade 2 anorexia was observed in 5 patients, and grade 3 neutropenia was observed in 2 patients. Grade 2 and grade 3 thrombocytopenia were observed in 2 and 3 patients, respectively. All treatment-related adverse events were improved by reduction or interruption of regorafenib. Five patients showed decreased serum albumin levels. Conclusion: Sorafenib and regorafenib sequential therapy presents a safe and effective treatment option for patients with advanced HCC.

© 2017 S. Karger AG, Basel


References

  1. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J: Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378-390.
  2. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z: 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 2009;10:25-34.
  3. Kudo M, Izumi N, Sakamoto M, Matsuyama Y, Ichida T, Nakashima O, Matsui O, Ku Y, Kokudo N, Makuuchi M: Survival analysis over 28 years of 173,378 patients with hepatocellular carcinoma in Japan. Liver Cancer 2016;5:190-197.
  4. Kudo M: Locoregional therapy for hepatocellular carcinoma. Liver Cancer 2015;4:163-164.
  5. Clinical practice guidelines for hepatocellular carcinoma differ between Japan, United States, and Europe. Liver Cancer 2015;4:85-95.
  6. Cheng AL, Kang YK, Lin DY, Park JW, Kudo M, Qin S, Chung HC, Song X, Xu J, Poggi G, Omata M, Pitman Lowenthal S, Lanzalone S, Yang L, Lechuga MJ, Raymond E: Sunitinib versus sorafenib in advanced hepatocellular cancer: Results of a randomized phase III trial. J Clin Oncol 2013;31:4067-4075.
  7. Cainap C, Qin S, Huang WT, Chung IJ, Pan H, Cheng Y, Kudo M, Kang YK, Chen PJ, Toh HC, Gorbunova V, Eskens FA, Qian J, McKee MD, Ricker JL, Carlson DM, El-Nowiem S: Linifanib versus sorafenib in patients with advanced hepatocellular carcinoma: results of a randomized phase III trial. J Clin Oncol 2015;33:172-179.
  8. Johnson PJ, Qin S, Park JW, Poon RT, Raoul JL, Philip PA, Hsu CH, Hu TH, Heo J, Xu J, Lu L, Chao Y, Boucher E, Han KH, Paik SW, Robles-Avina J, Kudo M, Yan L, Sobhonslidsuk A, Komov D, Decaens T, Tak WY, Jeng LB, Liu D, Ezzeddine R, Walters I, Cheng AL: Brivanib versus sorafenib as first-line therapy in patients with unresectable, advanced hepatocellular carcinoma: Results from the randomized phase III BRISK-FL study. J Clin Oncol 2013;31:3517-3524.
  9. Llovet JM, Decaens T, Raoul JL, Boucher E, Kudo M, Chang C, Kang YK, Assenat E, Lim HY, Boige V, Mathurin P, Fartoux L, Lin DY, Bruix J, Poon RT, Sherman M, Blanc JF, Finn RS, Tak WY, Chao Y, Ezzeddine R, Liu D, Walters I, Park JW: Brivanib in patients with advanced hepatocellular carcinoma who were intolerant to sorafenib or for whom sorafenib failed: results from the randomized phase III BRISK-PS study. J Clin Oncol 2013;31:3509-3516.
  10. Zhu AX, Kudo M, Assenat E, Cattan S, Kang YK, Lim HY, Poon RT, Blanc JF, Vogel A, Chen CL, Dorval E, Peck-Radosavljevic M, Santoro A, Daniele B, Furuse J, Jappe A, Perraud K, Anak O, Sellami DB, Chen LT: Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE-1 randomized clinical trial. JAMA 2014;312:57-67.
  11. Zhu AX, Park JO, Ryoo BY, Yen CJ, Poon R, Pastorelli D, Blanc JF, Chung HC, Baron AD, Pfiffer TE, Okusaka T, Kubackova K, Trojan J, Sastre J, Chau I, Chang SC, Abada PB, Yang L, Schwartz JD, Kudo M: Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol 2015;16:859-870.
  12. Kudo M: Molecular targeted therapy for hepatocellular carcinoma: where are we now? Liver Cancer 2015;4:I-VII.
  13. Bruix J, Qin S, Merle P, Granito A, Huang YH, Bodoky G, Pracht M, Yokosuka O, Rosmorduc O, Breder V, Gerolami R, Masi G, Ross PJ, Song T, Bronowicki JP, Ollivier-Hourmand I, Kudo M, Cheng AL, Llovet JM, Finn RS, LeBerre MA, Baumhauer A, Meinhardt G, Han G; RESORCE Investigators: Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2017;389:56-66.
  14. Kudo M: Regorafenib as second-line systemic therapy may change the treatment strategy and management paradigm for hepatocellular carcinoma. Liver Cancer 2016;5:235-244.
  15. Lencioni R, Llovet JM: Modified recist (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 2010;30:52-60.
  16. Wilhelm SM, Dumas J, Adnane L, Lynch M, Carter CA, Schutz G, Thierauch KH, Zopf D: Regorafenib (bay 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity. Int J Cancer 2011;129:245-255.
  17. Bruix J, Tak WY, Gasbarrini A, Santoro A, Colombo M, Lim HY, Mazzaferro V, Wiest R, Reig M, Wagner A, Bolondi L: Regorafenib as second-line therapy for intermediate or advanced hepatocellular carcinoma: multicentre, open-label, phase II safety study. Eur J Cancer 2013;49:3412-3419.
  18. Toyoda H, Kumada T, Tada T, Sone Y, Kaneoka Y, Maeda A: Tumor markers for hepatocellular carcinoma: Simple and significant predictors of outcome in patients with HCC. Liver Cancer 2015;4:126-136.
  19. Ueshima K, Kudo M, Takita M, Nagai T, Tatsumi C, Ueda T, Kitai S, Ishikawa E, Yada N, Inoue T, Hagiwara S, Minami Y, Chung H, Sakurai T: Des-γ-carboxyprothrombin may be a promising biomarker to determine the therapeutic efficacy of sorafenib for hepatocellular carcinoma. Dig Dis 2011;29:321-325.
  20. Kudo M: A new era of systemic therapy for hepatocellular carcinoma with regorafenib and lenvatinib. Liver Cancer 2017;6:177-184.
  21. Kudo M: Surveillance, diagnosis, treatment, and outcome of liver cancer in Japan. Liver Cancer 2015;4:39-50.
  22. Arizumi T, Ueshima K, Minami T, Kono M, Chishina H, Takita M, Kitai S, Inoue T, Yada N, Hagiwara S, Minami Y, Sakurai T, Nishida N, Kudo M: Effectiveness of sorafenib in patients with transcatheter arterial chemoembolization (TACE) refractory and intermediate-stage hepatocellular carcinoma. Liver Cancer 2015;4:253-262.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: October 17, 2017
Issue release date: October 2017

Number of Print Pages: 7
Number of Figures: 3
Number of Tables: 3

ISSN: 0257-2753 (Print)
eISSN: 1421-9875 (Online)

For additional information: https://www.karger.com/DDI


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