Clarence Yen1, Rohini Sharma1, Lorenza Rimassa2, Tadaaki Arizumi3, Dominik Bettinger4,5, Huay Yee Choo1, Tiziana Pressiani2, Michela E Burlone6, Mario Pirisi6, Laura Giordano2, Anisa Abdulrahman1, Masatoshi Kudo3, Robert Thimme4,5, Joong Won Park7, David James Pinato1. 1. Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, UK. 2. Medical Oncology and Haematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center, Milan, Italy. 3. Department of Gastroenterology and Hepatology, Kindai University School of Medicine, Osakasayama, Japan. 4. Department of Medicine II, University Medical Center, Freiburg, Germany. 5. Berta Ottenstein Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany. 6. Department of Translational Medicine, Università degli Studi del Piemonte Orientale "A. Avogadro," Novara, Italy. 7. Center for Liver Cancer, National Cancer Center Hospital, Goyang, South Korea.
Abstract
BACKGROUND: Level I evidence supports the use of sorafenib in patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma, where heterogeneity in efficacy exists due to varying clinicopathologic features of the disease. AIM: We evaluated whether prior treatment with curative or locoregional therapies influences sorafenib-specific survival. METHODS: From a prospective data set of 785 consecutive patients from international specialist centres, 264 patients (34%) were treatment naïve (TN) and 521 (66%) were pre-treated (PT), most frequently with transarterial chemoembolization (n = 413; 79%). The primary endpoint was overall survival (OS) from sorafenib initiation with prognostic factors tested on uni- and multivariate analyses. RESULTS: Median OS for the entire cohort was 9 months; the median sorafenib duration was 2.8 months, with discontinuation being secondary to progression (n = 454; 58%) or toxicity (n = 149; 19%). PT patients had significantly longer OS than TN patients (10.5 vs. 6.6 months; p < 0.001). Compared to TN patients, PT patients had a better Child-Pugh (CP) class (CP A: 57 vs. 47%; p < 0.001) and a lower BCLC stage (BCLC A-B, 40 vs. 30%; p = 0.007). PT status preserved an independent prognostic role (p = 0.002) following adjustment for BCLC stage, α-fetoprotein, CP class, aetiology, and post-sorafenib treatment status. PT patients were more likely to receive further anticancer treatment after sorafenib (31 vs. 9%; p < 0.001). CONCLUSION: Patients receiving sorafenib after having failed curative or locoregional therapies survive longer and are more likely to receive further treatment after sorafenib. This suggests an incremental benefit to OS from sequential exposure to multiple lines of therapy, justifying treatment stage migration in eligible patients.
BACKGROUND: Level I evidence supports the use of sorafenib in patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma, where heterogeneity in efficacy exists due to varying clinicopathologic features of the disease. AIM: We evaluated whether prior treatment with curative or locoregional therapies influences sorafenib-specific survival. METHODS: From a prospective data set of 785 consecutive patients from international specialist centres, 264 patients (34%) were treatment naïve (TN) and 521 (66%) were pre-treated (PT), most frequently with transarterial chemoembolization (n = 413; 79%). The primary endpoint was overall survival (OS) from sorafenib initiation with prognostic factors tested on uni- and multivariate analyses. RESULTS: Median OS for the entire cohort was 9 months; the median sorafenib duration was 2.8 months, with discontinuation being secondary to progression (n = 454; 58%) or toxicity (n = 149; 19%). PT patients had significantly longer OS than TN patients (10.5 vs. 6.6 months; p < 0.001). Compared to TN patients, PT patients had a better Child-Pugh (CP) class (CP A: 57 vs. 47%; p < 0.001) and a lower BCLC stage (BCLC A-B, 40 vs. 30%; p = 0.007). PT status preserved an independent prognostic role (p = 0.002) following adjustment for BCLC stage, α-fetoprotein, CP class, aetiology, and post-sorafenib treatment status. PT patients were more likely to receive further anticancer treatment after sorafenib (31 vs. 9%; p < 0.001). CONCLUSION: Patients receiving sorafenib after having failed curative or locoregional therapies survive longer and are more likely to receive further treatment after sorafenib. This suggests an incremental benefit to OS from sequential exposure to multiple lines of therapy, justifying treatment stage migration in eligible patients.
Authors: Richard Jackson; Eftychia-Eirini Psarelli; Sarah Berhane; Harun Khan; Philip Johnson Journal: J Clin Oncol Date: 2017-01-03 Impact factor: 44.544
Authors: Matthias Pinter; Wolfgang Sieghart; Ivo Graziadei; Wolfgang Vogel; Andreas Maieron; Robert Königsberg; Adalbert Weissmann; Gabriela Kornek; Christina Plank; Markus Peck-Radosavljevic Journal: Oncologist Date: 2009-01-14
Authors: T Pressiani; C Boni; L Rimassa; R Labianca; S Fagiuoli; S Salvagni; D Ferrari; E Cortesi; C Porta; C Mucciarini; L Latini; C Carnaghi; M Banzi; S Fanello; M De Giorgio; F R Lutman; G Torzilli; M A Tommasini; R Ceriani; G Covini; M C Tronconi; L Giordano; N Locopo; S Naimo; A Santoro Journal: Ann Oncol Date: 2012-10-05 Impact factor: 32.976
Authors: Jacques Ferlay; Isabelle Soerjomataram; Rajesh Dikshit; Sultan Eser; Colin Mathers; Marise Rebelo; Donald Maxwell Parkin; David Forman; Freddie Bray Journal: Int J Cancer Date: 2014-10-09 Impact factor: 7.396
Authors: Marcus A Wörns; Sandra Koch; Ina M Niederle; Jens U Marquardt; Marc Nguyen-Tat; Thomas Gamstätter; Marcus Schuchmann; Henning Schulze-Bergkamen; Peter R Galle; Arndt Weinmann Journal: Dig Liver Dis Date: 2012-11-21 Impact factor: 4.088
Authors: Dominik Bettinger; David J Pinato; Michael Schultheiss; Rohini Sharma; Lorenza Rimassa; Tiziana Pressiani; Michela E Burlone; Mario Pirisi; Masatoshi Kudo; Joong Won Park; Nico Buettner; Christoph Neumann-Haefelin; Tobias Boettler; Nasrin Abbasi-Senger; Horst Alheit; Wolfgang Baus; Oliver Blanck; Sabine Gerum; Mathias Guckenberger; Daniel Habermehl; Christian Ostheimer; Oliver Riesterer; Jörg Tamihardja; Anca-Ligia Grosu; Robert Thimme; Thomas Baptist Brunner; Eleni Gkika Journal: Liver Cancer Date: 2018-07-12 Impact factor: 11.740
Authors: Gauri Mishra; Anouk Dev; Eldho Paul; Wa Cheung; Jim Koukounaras; Ashu Jhamb; Ben Marginson; Beng Ghee Lim; Paul Simkin; Adina Borsaru; James Burnes; Mark Goodwin; Vivek Ramachandra; Manfred Spanger; John Lubel; Paul Gow; Siddharth Sood; Alexander Thompson; Marno Ryan; Amanda Nicoll; Sally Bell; Ammar Majeed; William Kemp; Stuart K Roberts Journal: BMC Cancer Date: 2020-05-29 Impact factor: 4.430
Authors: Xin Hui Chew; Rehena Sultana; Eshani N Mathew; David Chee Eng Ng; Richard H G Lo; Han Chong Toh; David Tai; Su Pin Choo; Brian Kim Poh Goh; Sean Xuexian Yan; Kelvin Siu Hoong Loke; Sue Ping Thang; Apoorva Gogna; Nanda Karaddi Venkatanarasimha; Aaron K T Tong; Fiona N N Moe; Jacelyn S S Chua; Reiko W T Ang; Aldwin D Ong; Ashley W Y Ng; Marjorie T Q Hoang; Chow Wei Too; Choon Hua Thng; Wan Ying Chan; Wanyi Kee; Jaclyn H M Chan; Farah Irani; Sum Leong; Kiat Hon Lim; Michael L C Wang; Pierce K H Chow Journal: Liver Cancer Date: 2021-04-07 Impact factor: 11.740