Francesco Tovoli1, Luca Ielasi2, Andrea Casadei-Gardini3, Alessandro Granito2, Francesco Giuseppe Foschi4, Giulia Rovesti5, Giulia Negrini2, Giulia Orsi5, Matteo Renzulli6, Fabio Piscaglia2. 1. Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. Electronic address: francesco.tovoli2@unibo.it. 2. Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. 3. Department of Medical Oncology, Istituto Scientifico Romagnolo per Lo Studio e Cura Dei Tumori, Meldola, Italy; Department of Oncology and Haematology, University Hospital of Modena, Modena, Italy. 4. Department of Internal Medicine, Degli Infermi Hospital, Faenza, Italy. 5. Department of Oncology and Haematology, University Hospital of Modena, Modena, Italy. 6. Unit of Radiology, Department of Diagnostic Medicine and Prevention, Sant'Orsola Hospital, University of Bologna, Bologna, Italy.
Abstract
BACKGROUND & AIMS: Sorafenib is associated with multiple adverse events (AEs), potentially causing its permanent interruption. It is unknown how physicians' experience has impacted on the management of these AEs and consequently on clinical outcomes. We aimed to assess whether AE management changed over time and if these modifications impacted on treatment duration and overall survival (OS). METHODS: We analysed the prospectively collected data of 338 consecutive patients who started sorafenib between January 2008 and December 2017 in 3 tertiary care centres in Italy. Patients were divided according to the starting date: Group A (2008-2012; n = 154), and Group B (2013-2017, n = 184). Baseline and follow-up data were compared. In the OS analysis, patients who received second-line treatments were censored when starting the new therapy. RESULTS: Baseline characteristics, AEs, and radiological response were consistent across groups. Patients in Group B received a lower median daily dose (425 vs. 568 mg/day, p <0.001) due to more frequent dose modifications. However, treatment duration was longer (5.8 vs. 4.1 months, p = 0.021) with a trend toward a higher cumulative dose in Group B. Notably, the OS was also higher (12.0 vs. 11.0 months, p = 0.003) with a sharp increase in the 2-year survival rate (28.1 vs. 18.4%, p = 0.003) in Group B. Multivariate time-dependent Cox regression analysis confirmed later period of treatment (2013-2017) as an independent predictor of survival (HR 0.728; 95%CI 0.581-0.937; p = 0.013). Unconsidered confounders were unlikely to affect these results at the sensitivity analysis. CONCLUSIONS: Experience in the management of sorafenib-related AEs prolongs treatment duration and survival. This factor should be considered in the design of future randomised clinical trials including a sorafenib treatment arm, as an underestimate of sample size may derive. LAY SUMMARY: Sorafenib has been the standard frontline systemic treatment for hepatocellular carcinoma for over a decade. Its tolerability is limited by different adverse events, which might lead to its permanent discontinuation in a sizeable proportion of patients. After a careful analysis of potential confounders, we demonstrated that the physicians' experience in managing adverse events related to sorafenib has improved over time, with longer treatment periods and less permanent discontinuation for toxicities. More importantly, these improvements also translated into longer patient survival. Our results have relevant repercussions in clinical practice and in the design of future clinical trials.
BACKGROUND & AIMS:Sorafenib is associated with multiple adverse events (AEs), potentially causing its permanent interruption. It is unknown how physicians' experience has impacted on the management of these AEs and consequently on clinical outcomes. We aimed to assess whether AE management changed over time and if these modifications impacted on treatment duration and overall survival (OS). METHODS: We analysed the prospectively collected data of 338 consecutive patients who started sorafenib between January 2008 and December 2017 in 3 tertiary care centres in Italy. Patients were divided according to the starting date: Group A (2008-2012; n = 154), and Group B (2013-2017, n = 184). Baseline and follow-up data were compared. In the OS analysis, patients who received second-line treatments were censored when starting the new therapy. RESULTS: Baseline characteristics, AEs, and radiological response were consistent across groups. Patients in Group B received a lower median daily dose (425 vs. 568 mg/day, p <0.001) due to more frequent dose modifications. However, treatment duration was longer (5.8 vs. 4.1 months, p = 0.021) with a trend toward a higher cumulative dose in Group B. Notably, the OS was also higher (12.0 vs. 11.0 months, p = 0.003) with a sharp increase in the 2-year survival rate (28.1 vs. 18.4%, p = 0.003) in Group B. Multivariate time-dependent Cox regression analysis confirmed later period of treatment (2013-2017) as an independent predictor of survival (HR 0.728; 95%CI 0.581-0.937; p = 0.013). Unconsidered confounders were unlikely to affect these results at the sensitivity analysis. CONCLUSIONS: Experience in the management of sorafenib-related AEs prolongs treatment duration and survival. This factor should be considered in the design of future randomised clinical trials including a sorafenib treatment arm, as an underestimate of sample size may derive. LAY SUMMARY:Sorafenib has been the standard frontline systemic treatment for hepatocellular carcinoma for over a decade. Its tolerability is limited by different adverse events, which might lead to its permanent discontinuation in a sizeable proportion of patients. After a careful analysis of potential confounders, we demonstrated that the physicians' experience in managing adverse events related to sorafenib has improved over time, with longer treatment periods and less permanent discontinuation for toxicities. More importantly, these improvements also translated into longer patient survival. Our results have relevant repercussions in clinical practice and in the design of future clinical trials.
Authors: Francesco Tovoli; Vincenzo Dadduzio; Stefania De Lorenzo; Lorenza Rimassa; Gianluca Masi; Massimo Iavarone; Fabio Marra; Ingrid Garajova; Maria Pia Brizzi; Bruno Daniele; Franco Trevisani; Carlo Messina; Francesco Di Clemente; Sara Pini; Giuseppe Cabibbo; Alessandro Granito; Mario Domenico Rizzato; Vittorina Zagonel; Giovanni Brandi; Tiziana Pressiani; Piera Federico; Caterina Vivaldi; Irene Bergna; Claudia Campani; Fabio Piscaglia Journal: Liver Cancer Date: 2021-06-15 Impact factor: 11.740
Authors: Matteo Renzulli; Nicolò Brandi; Anna Pecorelli; Luigi Vincenzo Pastore; Alessandro Granito; Giuseppe Martinese; Francesco Tovoli; Mario Simonetti; Elton Dajti; Antonio Colecchia; Rita Golfieri Journal: Diagnostics (Basel) Date: 2022-03-29
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