Saur Hajiev1, Elias Allara1,2, Leila Motedayеn Aval1, Tadaaki Arizumi3, Dominik Bettinger4,5, Mario Pirisi6, Lorenza Rimassa7,8, Tiziana Pressiani7, Nicola Personeni7,8, Laura Giordano7, Masatoshi Kudo3, Robert Thimme4, Joong-Won Park9, Tamar H Taddei10, David E Kaplan10, Ramya Ramaswami1, David J Pinato1, Rohini Sharma11. 1. Division of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK. 2. Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. 3. Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka-Sayama, 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, Novara, Italy. 7. Medical Oncology and Hematology Unit, Humanitas Cancer Center, Humanitas Clinical and Research Center-IRCCS, Rozzano (Milan), Italy. 8. Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (Milan), Italy. 9. National Cancer Centre Hospital, Goyang, South Korea. 10. University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. 11. Division of Surgery and Cancer, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK. r.sharma@imperial.ac.uk.
Abstract
BACKGROUND: There is no consensus on the effect of sorafenib dosing on efficacy and toxicity in elderly patients with hepatocellular carcinoma (HCC). Older patients are often empirically started on low-dose therapy with the aim to avoid toxicities while maximising clinical efficacy. We aimed to verify whether age impacts on overall survival (OS) and whether a reduced starting dose impacts on OS or toxicity experienced by the elderly. METHODS: In an international, multicentre cohort study, outcomes for those aged <75 or ≥75 years were determined while accounting for common prognostic factors and demographic characteristics in univariable and multivariable models. RESULTS: Five thousand five hundred and ninety-eight patients were recruited; 792 (14.1%) were aged ≥75 years. The elderly were more likely to have larger tumours (>7 cm) (39 vs 33%, p < 0.01) with preserved liver function (67 vs 57.7%) (p < 0.01). No difference in the median OS of those aged ≥75 years and <75 was noted (7.3 months vs 7.2 months; HR 1.00 (95% CI 0.93-1.08), p = 0.97). There was no relationship between starting dose of sorafenib 800 mg vs 400 mg/200 mg and OS between those <75 and ≥75 years. The elderly experienced a similar overall incidence of grade 2-4 sorafenib-related toxicity compared to <75 years (63.5 vs 56.7%, p = 0.11). However, the elderly were more likely to discontinue sorafenib due to toxicity (27.0 vs 21.6%, p < 0.01). This did not vary between different starting doses of sorafenib. CONCLUSIONS: Clinical outcomes in the elderly is equivalent to patients aged <75 years, independent of dose of sorafenib prescribed.
BACKGROUND: There is no consensus on the effect of sorafenib dosing on efficacy and toxicity in elderly patients with hepatocellular carcinoma (HCC). Older patients are often empirically started on low-dose therapy with the aim to avoid toxicities while maximising clinical efficacy. We aimed to verify whether age impacts on overall survival (OS) and whether a reduced starting dose impacts on OS or toxicity experienced by the elderly. METHODS: In an international, multicentre cohort study, outcomes for those aged <75 or ≥75 years were determined while accounting for common prognostic factors and demographic characteristics in univariable and multivariable models. RESULTS: Five thousand five hundred and ninety-eight patients were recruited; 792 (14.1%) were aged ≥75 years. The elderly were more likely to have larger tumours (>7 cm) (39 vs 33%, p < 0.01) with preserved liver function (67 vs 57.7%) (p < 0.01). No difference in the median OS of those aged ≥75 years and <75 was noted (7.3 months vs 7.2 months; HR 1.00 (95% CI 0.93-1.08), p = 0.97). There was no relationship between starting dose of sorafenib 800 mg vs 400 mg/200 mg and OS between those <75 and ≥75 years. The elderly experienced a similar overall incidence of grade 2-4 sorafenib-related toxicity compared to <75 years (63.5 vs 56.7%, p = 0.11). However, the elderly were more likely to discontinue sorafenib due to toxicity (27.0 vs 21.6%, p < 0.01). This did not vary between different starting doses of sorafenib. CONCLUSIONS: Clinical outcomes in the elderly is equivalent to patients aged <75 years, independent of dose of sorafenib prescribed.
Authors: Kim A Reiss; Shun Yu; Ronac Mamtani; Rajni Mehta; Kathryn D'Addeo; E Paul Wileyto; Tamar H Taddei; David E Kaplan Journal: J Clin Oncol Date: 2017-09-05 Impact factor: 44.544
Authors: Lore Decoster; Cindy Kenis; Katrien Van Puyvelde; Johan Flamaing; Godelieve Conings; Jacques De Grève; Tony Mets; Koen Milisen; Jean Pierre Lobelle; Hans Wildiers Journal: J Geriatr Oncol Date: 2013-05-23 Impact factor: 3.599
Authors: J Howell; D J Pinato; R Ramaswami; D Bettinger; T Arizumi; C Ferrari; C Yen; A Gibbin; M E Burlone; G Guaschino; L Sellers; J Black; M Pirisi; M Kudo; R Thimme; J-W Park; R Sharma Journal: Aliment Pharmacol Ther Date: 2017-03-02 Impact factor: 8.171
Authors: Josep M Llovet; Sergio Ricci; Vincenzo Mazzaferro; Philip Hilgard; Edward Gane; Jean-Frédéric Blanc; Andre Cosme de Oliveira; Armando Santoro; Jean-Luc Raoul; Alejandro Forner; Myron Schwartz; Camillo Porta; Stefan Zeuzem; Luigi Bolondi; Tim F Greten; Peter R Galle; Jean-François Seitz; Ivan Borbath; Dieter Häussinger; Tom Giannaris; Minghua Shan; Marius Moscovici; Dimitris Voliotis; Jordi Bruix Journal: N Engl J Med Date: 2008-07-24 Impact factor: 91.245
Authors: Guilherme Nader Marta; Leonardo G da Fonseca; Maria Ignez Braghiroli; Fernando Moura; Paulo M Hoff; Jorge Sabbaga Journal: Clinics (Sao Paulo) Date: 2021-01-22 Impact factor: 2.365
Authors: Dominik Safcak; Sylvia Drazilova; Jakub Gazda; Igor Andrasina; Svetlana Adamcova-Selcanova; Lea Balazova; Radovan Barila; Michal Mego; Marek Rac; Lubomir Skladany; Miroslav Zigrai; Martin Janicko; Peter Jarcuska Journal: J Clin Med Date: 2022-07-19 Impact factor: 4.964