Adam Doyle1, Philip Marsh1, Raghubinder Gill2, Marcia Rodov2, Waled Mohsen2, Poornima Varma3, Thai Hong4, Simone I Strasser2, Sally Bell4, Marno Ryan4, Amanda Nicoll3,5, John Lubel5, Paul J Gow6, Michael Anthony Fink7, Stuart Roberts8, William Kemp8, Ian Kronborg9, Niranjan Arachchi9, Virginia Knight1, Anouk Dev1. 1. a Department of Gastroenterology , Monash Health , Victoria , Australia ; 2. b AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , New South Wales , Australia ; 3. c Department of Gastroenterology and Hepatology , Royal Melbourne Hospital , Victoria , Australia ; 4. d Department of Gastroenterology , St Vincent's Hospital , Victoria , Australia ; 5. e Department of Gastroenterology , Box Hill Hospital, Eastern Health , Victoria , Australia ; 6. f Department of Gastroenterology , Austin Health , Victoria , Australia ; 7. g Department of Surgery , Austin Health , Melbourne , Victoria , Australia ; 8. h Department of Gastroenterology , Alfred Hospital , Victoria , Australia ; 9. i Department of Gastroenterology , Western Hospital , Victoria , Australia.
Abstract
OBJECTIVE: Sorafenib is an oral multikinase inhibitor that improves survival in advanced hepatocellular carcinoma (HCC). In the absence of alternative therapies, sorafenib is often continued despite advancing liver disease or tumour progression. Real world studies are important to better characterise outcomes in these populations. Our aim was to review patterns of sorafenib use across eight Australian tertiary hospitals, defining variables associated with clinical outcomes. MATERIAL AND METHODS: Retrospective cohort study of medical records of 320 patients treated with sorafenib for HCC. Baseline clinical parameters, dosage, adverse effects, and survival from initiation of treatment were collected. Time to radiological progression and 3-month alpha-fetoprotein (AFP) levels were available for a subset of patients. RESULTS: Adverse effects occurred in 79% of patients, requiring dose reduction in 31% of patients. Multivariate analysis identified an increased rate of mortality with Child-Pugh C (HR 5.52, p = 0.012), ECOG performance status 2-3 (HR 2.84, p = 0.001), and extrahepatic metastases (HR 1.54, p = 0.04), and decreased rate of mortality with an AFP reduction of at least 20% at 3 months (HR 0.38, p = 0.001). An increased rate of radiological progression was associated with ECOG performance status 2-3 (HR 2.34, p = 0.041), whilst a decreased rate of radiological progression was associated with development of on-treatment diarrhoea (HR 0.55, p = 0.015). CONCLUSIONS: Survival in patients with Child-Pugh C liver function or advanced functional impairment treated with sorafenib is poor and thus routine use of this agent in these patients does not appear justified, particularly given the high rate of adverse effects. AFP concentration on therapy may help identify favourable response to treatment.
OBJECTIVE:Sorafenib is an oral multikinase inhibitor that improves survival in advanced hepatocellular carcinoma (HCC). In the absence of alternative therapies, sorafenib is often continued despite advancing liver disease or tumour progression. Real world studies are important to better characterise outcomes in these populations. Our aim was to review patterns of sorafenib use across eight Australian tertiary hospitals, defining variables associated with clinical outcomes. MATERIAL AND METHODS: Retrospective cohort study of medical records of 320 patients treated with sorafenib for HCC. Baseline clinical parameters, dosage, adverse effects, and survival from initiation of treatment were collected. Time to radiological progression and 3-month alpha-fetoprotein (AFP) levels were available for a subset of patients. RESULTS: Adverse effects occurred in 79% of patients, requiring dose reduction in 31% of patients. Multivariate analysis identified an increased rate of mortality with Child-Pugh C (HR 5.52, p = 0.012), ECOG performance status 2-3 (HR 2.84, p = 0.001), and extrahepatic metastases (HR 1.54, p = 0.04), and decreased rate of mortality with an AFP reduction of at least 20% at 3 months (HR 0.38, p = 0.001). An increased rate of radiological progression was associated with ECOG performance status 2-3 (HR 2.34, p = 0.041), whilst a decreased rate of radiological progression was associated with development of on-treatment diarrhoea (HR 0.55, p = 0.015). CONCLUSIONS: Survival in patients with Child-Pugh C liver function or advanced functional impairment treated with sorafenib is poor and thus routine use of this agent in these patients does not appear justified, particularly given the high rate of adverse effects. AFP concentration on therapy may help identify favourable response to treatment.
Authors: Kurvi Patwala; David Stephen Prince; Yael Celermajer; Waafiqa Alam; Eldho Paul; Simone Irene Strasser; Geoffrey William McCaughan; Paul Gow; Siddharth Sood; Elise Murphy; Stuart Roberts; Elliot Freeman; Elizabeth Stratton; Scott Anthony Davison; Miriam Tania Levy; McCawley Clark-Dickson; Vi Nguyen; Sally Bell; Amanda Nicoll; Ashley Bloom; Alice Unah Lee; Marno Ryan; Jessica Howell; Zina Valaydon; Alexandra Mack; Ken Liu; Anouk Dev Journal: Hepatol Int Date: 2022-08-25 Impact factor: 9.029