Sorafenib Use in Hepatocellular Carcinoma: More Questions Than Answers
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lmost 2 years ago, an article with the title “Field-Practice Study of Sorafenib Therapy for Hepatocellular Carcinoma: A Prospective Multicenter Study in Italy” by Iavarone et al. was published in this journal.1 To date, the conclusions of this article continue to stimulate discussion. In their attempt to better identify the role of sorafenib in the setting of broad nonclinical trial use, Iavarone et al. conducted an observational study right after the phase III randomized study of sorafenib versus placebo (SHARP trial) reported an improved median overall survival (OS) outcome of 10.7 versus 7.9 months in favor of sorafenib.2 The key outcomes of this observational study conducted by Iavarone et al. were a similar median survival of 10.5 months and a toxicity profile analagous to the SHARP trial. The key issues under question are the correlation of improved outcome in association with a lower dose of sorafenib; the prediction of outcome based on side effects; and the use of the modified Response Evaluation Criteria in Solid Tumors (mRECIST). The intent of this editorial is to help elucidate those points and draw some practical conclusions that apply to the use of sorafenib in the clinical setting.
Sorafenib Dosing and Outcome The observation of Iavarone et al. regarding sorafenib dosing and outcome is intriguing—but it is also limited by its retrospective nature, as the authors fairly acknowledge. The duration of treatment between patients who underwent a dose reduction and patients who received full dose sorafenib resulted in prolonged treatment exposure (6.8 versus 3 months), even though not necessarily an increased cumulative dose. OS was 21.6 months (95% confidence interval [CI] 13.6-29.6) for patients Abbreviations: OS, overall survival; pERK, phosphorylated ERK; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; VEGF, vascular endothelial growth factor. Address reprint requests to: Ghassan K Abou-Alfa, M.D., Memorial SloanKettering Cancer Center, 300 East 66th St., New York, NY 10065. E-mail: [email protected]; fax: 646-888-4255. Received October 1, 2013; accepted January 26, 2014. C 2014 by the American Association for the Study of Liver Diseases. Copyright V View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.27044 Potential conflict of interest: Dr. Abou-Alfa received grants from Bayer.
who received a half-dose of sorafenib for 70% of the treatment period, compared to 9.6 months (95% CI 6.9-12.3) for the patients who maintained full dosing or had a dose reduced for
A
lmost 2 years ago, an article with the title “Field-Practice Study of Sorafenib Therapy for Hepatocellular Carcinoma: A Prospective Multicenter Study in Italy” by Iavarone et al. was published in this journal.1 To date, the conclusions of this article continue to stimulate discussion. In their attempt to better identify the role of sorafenib in the setting of broad nonclinical trial use, Iavarone et al. conducted an observational study right after the phase III randomized study of sorafenib versus placebo (SHARP trial) reported an improved median overall survival (OS) outcome of 10.7 versus 7.9 months in favor of sorafenib.2 The key outcomes of this observational study conducted by Iavarone et al. were a similar median survival of 10.5 months and a toxicity profile analagous to the SHARP trial. The key issues under question are the correlation of improved outcome in association with a lower dose of sorafenib; the prediction of outcome based on side effects; and the use of the modified Response Evaluation Criteria in Solid Tumors (mRECIST). The intent of this editorial is to help elucidate those points and draw some practical conclusions that apply to the use of sorafenib in the clinical setting.
Sorafenib Dosing and Outcome The observation of Iavarone et al. regarding sorafenib dosing and outcome is intriguing—but it is also limited by its retrospective nature, as the authors fairly acknowledge. The duration of treatment between patients who underwent a dose reduction and patients who received full dose sorafenib resulted in prolonged treatment exposure (6.8 versus 3 months), even though not necessarily an increased cumulative dose. OS was 21.6 months (95% confidence interval [CI] 13.6-29.6) for patients Abbreviations: OS, overall survival; pERK, phosphorylated ERK; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumors; VEGF, vascular endothelial growth factor. Address reprint requests to: Ghassan K Abou-Alfa, M.D., Memorial SloanKettering Cancer Center, 300 East 66th St., New York, NY 10065. E-mail: [email protected]; fax: 646-888-4255. Received October 1, 2013; accepted January 26, 2014. C 2014 by the American Association for the Study of Liver Diseases. Copyright V View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.27044 Potential conflict of interest: Dr. Abou-Alfa received grants from Bayer.
who received a half-dose of sorafenib for 70% of the treatment period, compared to 9.6 months (95% CI 6.9-12.3) for the patients who maintained full dosing or had a dose reduced for
