Impact of adjuvant sorafenib treatment after local ablation for HCC in the phase II SORAMIC trial
Max Seidensticker,
Osman Öcal,
Kerstin Schütte,
Peter Malfertheiner,
Thomas Berg,
Christian Loewe,
Heinz Josef Klümpen,
Otto van Delden,
Muzaffer Reha Ümütlü,
Najib Ben Khaled,
Enrico Narciso de Toni,
Ricarda Seidensticker,
Ali Aghdassi,
Albert Tran,
Jean-Pierre Bronowicki,
Bora Peynircioglu,
Bruno Sangro,
Maciej Pech,
Jens Ricke
Affiliations
Max Seidensticker
Department of Radiology, University Hospital, LMU Munich, Munich, Germany
Osman Öcal
Department of Radiology, University Hospital, LMU Munich, Munich, Germany
Kerstin Schütte
Department of Internal Medicine and Gastroenterology, Niels-Stensen-Kliniken Marienhospital, Osnabrück, Germany
Peter Malfertheiner
Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
Thomas Berg
Klinik und Poliklinik für Gastroenterologie, Sektion Hepatologie, Universitätsklinikum Leipzig, Germany
Christian Loewe
Section of Cardiovascular and Interventional Radiology, Department of Bioimaging and Image-Guided Therapy, Medical University of Vienna, Vienna, Austria
Heinz Josef Klümpen
Department of Medical Oncology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
Otto van Delden
Department of Radiology and Nuclear Medicine, Academic University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands
Muzaffer Reha Ümütlü
Department of Radiology, University Hospital, LMU Munich, Munich, Germany
Najib Ben Khaled
Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
Enrico Narciso de Toni
Department of Medicine II, University Hospital, LMU Munich, Munich, Germany
Ricarda Seidensticker
Department of Radiology, University Hospital, LMU Munich, Munich, Germany
Ali Aghdassi
Department of Medicine A, University Medicine Greifswald, 17489 Greifswald, Germany
Albert Tran
Pôle Appareil Digestif, Hôpital l'Archet 2, CHU Nice, Route Saint-Antoine de Ginestière - BP 3079, Nice, France
Jean-Pierre Bronowicki
Department of Hepatology, INSERM U1254, Hôpital de Brabois, CHU de Nancy, University of Lorraine, Nancy, France
Bora Peynircioglu
Department of Radiology, Hacettepe University Hospital, Ankara, Turkey
Bruno Sangro
Liver Unit, Clínica Universidad de Navarra and CIBEREHD, Pamplona, Spain
Maciej Pech
Department of Radiology and Nuclear Medicine, University of Magdeburg, Magdeburg, Germany
Jens Ricke
Department of Radiology, University Hospital, LMU Munich, Munich, Germany; Corresponding author. Address: Department of Radiology, University Hospital, Ludwig Maximilian University of Munich, Marchioninistrasse 15, 81377 Munich, Germany. Tel: +49-4400-72750..
Background & Aims: The aim of the study was to evaluate the efficacy and safety of adjuvant sorafenib treatment compared with placebo in patients with hepatocellular carcinoma who underwent local ablation. Methods: The SORAMIC trial is a randomised controlled trial with diagnostic, local ablation, and palliative sub-study arms. After initial imaging within the diagnostic study, patients were assigned to local ablation or palliative arms. In the local ablation cohort, patients were randomised 1:1 to local ablation + sorafenib vs. local ablation + placebo. The primary endpoint was time-to-recurrence (TTR). Secondary endpoints were local control rate and safety in terms of adverse events and quality-of-life. Results: The recruitment was terminated prematurely after 104 patients owing to slow recruitment. One patient was excluded because of a technical failure. Fifty-four patients were randomised to local ablation + sorafenib and 49 to local ablation + placebo. Eighty-eight patients who underwent standardised follow-up imaging comprised the per-protocol population. The median TTR was 15.2 months in the sorafenib arm and 16.4 months in the placebo arm (hazard ratio 1.1; 95% CI 0.53–2.2; p = 0.82). Out of 136 lesions ablated within the trial, there was no difference in local recurrence rate between sorafenib (6/69, 8.6%) and placebo groups (5/67, 5.9%; p = 0.792).Overall (92.5% vs. 71.4%, p = 0.008) and drug-related (81.4% vs. 55.1%, p = 0.003) adverse events were more common in the sorafenib arm compared with the placebo arm. Dose reduction because of adverse events were common in the sorafenib arm (79.6% vs. 30.6%, p <0.001). Conclusions: Adjuvant sorafenib did not improve in TTR or local control rate after local ablation in patients with hepatocellular carcinoma within the limitations of an early terminated trial. Impact and implications: Local ablation is the standard of care treatment in patients with early stages of hepatocellular carcinoma, along with surgical therapies. However, there is a risk of disease recurrence during follow-up. Sorafenib, an oral medication, is a routinely used treatment for patients with advanced hepatocellular carcinoma. This study found that sorafenib treatment after local ablation in people with early hepatocellular carcinoma did not significantly improve the disease-free period compared with placebo. Clinical trial number: EudraCT 2009-012576-27, NCT01126645.
