Mairéad Geraldine McNamara1, Astrid E Slagter2, Christina Nuttall3, Melissa Frizziero3, Rille Pihlak4, Angela Lamarca3, Noor Tariq4, Juan W Valle4, Richard A Hubner3, Jennifer J Knox5, Eitan Amir5. 1. Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, M20 4BX, UK; University of Manchester, Division of Cancer Sciences, Manchester, M20 4BX, UK. Electronic address: Mairead.McNamara@christie.nhs.uk. 2. Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, M20 4BX, UK; University of Amsterdam, the Netherlands. 3. Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, M20 4BX, UK. 4. Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, M20 4BX, UK; University of Manchester, Division of Cancer Sciences, Manchester, M20 4BX, UK. 5. Department of Medical Oncology, Princess Margaret Cancer Centre/University of Toronto, 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada.
Abstract
BACKGROUND: Sorafenib has demonstrated survival benefit in first-line treatment of advanced hepatocellular carcinoma (HCC); utility of sorafenib in patients with advanced HCC and Child-Pugh B (CP-B) liver function remains a subject of debate. METHODS: A systematic review identified studies using first-line sorafenib in patients with advanced HCC and CP-A/B liver function. Meta-regression analysis comprising linear regression was conducted to explore the association between the baseline factors and overall survival (OS). Differences between efficacy/safety and tolerability parameters were explored using meta-analysis. RESULTS: Thirty studies (12 Asian) comprising 8678 patients (August 2002 - September 2012) were included (four randomised controlled trials, 26 cohort studies). Median age was 61 years and 83% were men. Hepatitis B/C status was positive in 35%/22%, respectively. The CP status was available for 8577 patients (99%); CP-A, 79% and CP-B, 19%. Median OS on sorafenib for entire cohort was 7.2 months; 8.8 months in CP-A and 4.6 months in CP-B. Multivariable meta-regression analysis showed significant negative association between OS and proportion of patients with the Eastern Cooperative Oncology Group performance status 2 (P = 0.04) and CP-B liver function (P = 0.001). Among four studies reporting multivariable comparison of the CP status, CP-B was associated with significantly worse OS (P < 0.001). There were no differences in the response rate to sorafenib between patients with CP-A (4.6%) and CP-B (4.2%) liver function. Safety and tolerability were similar; 35% of patients with CP-A/B liver function developed grade III/IV adverse events (P = 0.7). Meta-regression analysis showed similar rates of treatment discontinuation without progression (P = 0.31) and treatment-related death (P = 0.94) in patients with CP-B liver function. CONCLUSION: CP-B liver function (versus CP-A) is associated with worse OS (but the similar response rate, safety and tolerability of first-line sorafenib, is unlikely to be clinically meaningful).
BACKGROUND:Sorafenib has demonstrated survival benefit in first-line treatment of advanced hepatocellular carcinoma (HCC); utility of sorafenib in patients with advanced HCC and Child-Pugh B (CP-B) liver function remains a subject of debate. METHODS: A systematic review identified studies using first-line sorafenib in patients with advanced HCC and CP-A/B liver function. Meta-regression analysis comprising linear regression was conducted to explore the association between the baseline factors and overall survival (OS). Differences between efficacy/safety and tolerability parameters were explored using meta-analysis. RESULTS: Thirty studies (12 Asian) comprising 8678 patients (August 2002 - September 2012) were included (four randomised controlled trials, 26 cohort studies). Median age was 61 years and 83% were men. Hepatitis B/C status was positive in 35%/22%, respectively. The CP status was available for 8577 patients (99%); CP-A, 79% and CP-B, 19%. Median OS on sorafenib for entire cohort was 7.2 months; 8.8 months in CP-A and 4.6 months in CP-B. Multivariable meta-regression analysis showed significant negative association between OS and proportion of patients with the Eastern Cooperative Oncology Group performance status 2 (P = 0.04) and CP-B liver function (P = 0.001). Among four studies reporting multivariable comparison of the CP status, CP-B was associated with significantly worse OS (P < 0.001). There were no differences in the response rate to sorafenib between patients with CP-A (4.6%) and CP-B (4.2%) liver function. Safety and tolerability were similar; 35% of patients with CP-A/B liver function developed grade III/IV adverse events (P = 0.7). Meta-regression analysis showed similar rates of treatment discontinuation without progression (P = 0.31) and treatment-related death (P = 0.94) in patients with CP-B liver function. CONCLUSION:CP-B liver function (versus CP-A) is associated with worse OS (but the similar response rate, safety and tolerability of first-line sorafenib, is unlikely to be clinically meaningful).
Authors: Hee Ho Chu; Jin Hyoung Kim; Ju Hyun Shim; Sang Min Yoon; Pyeong Hwa Kim; Ibrahim Alrashidi Journal: Cancers (Basel) Date: 2020-04-29 Impact factor: 6.639
Authors: Kim Freese; Tatjana Seitz; Peter Dietrich; Serene M L Lee; Wolfgang E Thasler; Anja Bosserhoff; Claus Hellerbrand Journal: Cancers (Basel) Date: 2019-10-18 Impact factor: 6.639