Field-practice study of sorafenib therapy for hepatocellular carcinoma: A prospective multicenter study in Italy

Authors

  • Massimo Iavarone,

    1. A.M. & A. Migliavacca Center for Liver Disease, 1st Division of Gastroenterology, Fondazione IRCCS Ca' Granda Maggiore Hospital, University of Milan, Milan, Italy
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  • Giuseppe Cabibbo,

    1. Sezione di Gastroenterologia, DIBIMIS, University of Palermo, Palermo, Italy
    2. Dipartimento di Biopatologia e Metodologie Biomediche, University of Palermo, Palermo, Italy
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  • Fabio Piscaglia,

    1. Division of Internal Medicine, Department of Digestive Disease and Internal Medicine, General and University S. Orsola-Malpighi Hospital, Bologna, Italy
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  • Claudio Zavaglia,

    1. Struttura Complessa di Epatologia e Gastroenterologia, Azienda Ospedaliera Niguarda Ca' Granda, Milan, Italy
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  • Antonio Grieco,

    1. Institute of Internal Medicine, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy
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  • Erica Villa,

    1. Dipartimento di Medicina Interna, UO Gastroenterologia, Università di Modena & Reggio Emilia, Modena, Italy
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  • Calogero Cammà,

    1. Sezione di Gastroenterologia, DIBIMIS, University of Palermo, Palermo, Italy
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  • Massimo Colombo,

    Corresponding author
    1. A.M. & A. Migliavacca Center for Liver Disease, 1st Division of Gastroenterology, Fondazione IRCCS Ca' Granda Maggiore Hospital, University of Milan, Milan, Italy
    • 1st Division of Gastroenterology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Università degli Studi di Milano, Via F. Sforza 35, 20122 Milan, Italy
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    • fax: 39-0250320410

  • on behalf of the SOFIA (SOraFenib Italian Assessment) study group

    1. A.M. & A. Migliavacca Center for Liver Disease, 1st Division of Gastroenterology, Fondazione IRCCS Ca' Granda Maggiore Hospital, University of Milan, Milan, Italy
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  • Potential conflict of interest: Fabio Piscaglia receives consulting and speaking support from Bayer and Bracco. Massimo Colombo has received grant and research support from Schering-Plough, Roche, Bristol-Myers Squibb, Gilead, and Bayer and is on the Advisory Boards of Schering-Plough, Roche, Novartis, Vertex, Bristol-Myers Squibb, Gilead, Bayer, and Tibotec. He also receives speaking and teaching support from Schering-Plough, Roche, Novartis, Vertex, Bristol-Myers Squibb, Gilead, and Bayer. The other authors have nothing to report. Travel support provided by Gilead (M. I.) and Bayer (G. C.).

  • SOFIA study group: Milan1—Massimo Iavarone, Angelo Sangiovanni, Sara Vavassori, Raffaella Romeo, and Massimo Colombo; Palermo2,3—Giuseppe Cabibbo, Vito Di Marco, Calogero Cammà, and Antonio Craxì; Bologna4—Alberto Borghi, Alessandro Granito, Fabio Piscaglia, and Luigi Bolondi; Milan5—Claudio Zavaglia, Aldo Airoldi, and Giovambattista Pinzello; Rome6—Marco Biolato, Simona Racco, Maurizio Pompili, and Antonio Grieco; Modena7—Barbara Lei, Nicola De Maria, and Erica Villa.

Abstract

A multicenter randomized controlled trial established sorafenib as a standard of care for patients with advanced hepatocellular carcinoma (HCC). Because the study was prematurely interrupted due to survival benefits in the sorafenib arm, we conducted an observational study to adequately assess risks and benefits of this regimen in field practice. Starting in 2008, all clinically compensated patients with advanced HCC and those with an intermediate HCC who were unfit or failed to respond to ablative therapies were consecutively evaluated in six liver centers in Italy, for tolerability as well as radiologic and survival response to 800-mg/d sorafenib therapy. Treatment was down-dosed or interrupted according to drug label. Two hundred ninety-six patients (88% Child-Pugh A, 75% Barcelona Clinic Liver Cancer [BCLC]-C, and 25% BCLC-B) received sorafenib for 3.8 months (95% CI 3.3-4.4). Two hundred sixty-nine (91%) patients experienced at least one adverse event (AE), whereas 161 (54%) had to reduce dosing. Treatment was interrupted in 103 (44%) for disease progression, in 95 (40%) for an AE, and in 38 (16%) for liver deterioration. The median survival was 10.5 months in the overall cohort, 8.4 months in BCLC-C versus 20.6 months in BCLC-B patients (P < 0.0001), and 21.6 months in the 77 patients treated for >70% of the time with a half dose versus 9.6 months in the 219 patients treated for >70% of the time with a full dose. At month 2 of treatment, the overall radiologic response was 8%. Eastern Cooperative Oncology Group performance status, macrovascular invasion, extrahepatic spread of the tumor, radiologic response at month 2, and sorafenib dosing were independent predictors of shortened survival. Conclusion: Overall, safety, effectiveness, and generalizability of sorafenib therapy in HCC was validated in field practice. The effectiveness of half-dosed sorafenib may have implications for tailored therapy. (HEPATOLOGY 2011)

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