Maria Reig1, Ferran Torres2, Carlos Rodriguez-Lope1, Alejandro Forner1, Neus LLarch1, Jordi Rimola3, Anna Darnell4, José Ríos2, Carmen Ayuso3, Jordi Bruix5. 1. Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain. 2. Biostatistics and Data Management Core Facility, IDIBAPS, Hospital Clínic Barcelona, Spain; Biostatistics Unit, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain. 3. Barcelona Clinic Liver Cancer (BCLC) Group, Radiology Department, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain. 4. Barcelona Clinic Liver Cancer (BCLC) Group, Radiology Department, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain. 5. Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain. Electronic address: jbruix@clinic.ub.es.
Abstract
BACKGROUND & AIMS: There are no clinical data/markers to predict improved survival in patients with hepatocellular carcinoma treated with sorafenib. Majority of sorafenib adverse events appear within the first 60 days of treatment and studies correlating them with outcome are needed. METHODS: We prospectively studied 147 hepatocellular carcinoma patients (97% cirrhotic, 82% Child-Pugh A, BCLC-B 77, BCLC-C 69) treated with sorafenib. Follow-up included monthly clinical and laboratory monitoring and tumor staging at week 4 and every 8 weeks. RESULTS: After a median follow up of 11.6 months (treatment duration 6.7 months), time to progression and overall survival were 5.1 and 12.7 months. All but one patient presented at least one adverse event (median time to appearance 56 days). Time dependent covariate analysis (HR [95% CI]) identified baseline performance status (2.86 [1.75 to 4.55], p<0.001), BCLC (1.69 [1.18 to 2.50], p = 0.005), and dermatologic adverse event requiring dose adjustment within the first 60 days (0.58 [0.36 to 0.92], p = 0.022) as independent predictors of better outcome. Other early adverse events did not have an impact in outcome. The predictive value of dermatologic adverse events for survival was confirmed by the landmark analysis (p = 0.0270). CONCLUSIONS: Development of dermatologic adverse events within 60 days of sorafenib initiation is associated with better survival. Therefore, this should not to be taken as a negative event and discourage treatment maintenance. Likewise, second line clinical trials should be designed and/or evaluated considering this information to avoid significant bias.
BACKGROUND & AIMS: There are no clinical data/markers to predict improved survival in patients with hepatocellular carcinoma treated with sorafenib. Majority of sorafenib adverse events appear within the first 60 days of treatment and studies correlating them with outcome are needed. METHODS: We prospectively studied 147 hepatocellular carcinomapatients (97% cirrhotic, 82% Child-Pugh A, BCLC-B 77, BCLC-C 69) treated with sorafenib. Follow-up included monthly clinical and laboratory monitoring and tumor staging at week 4 and every 8 weeks. RESULTS: After a median follow up of 11.6 months (treatment duration 6.7 months), time to progression and overall survival were 5.1 and 12.7 months. All but one patient presented at least one adverse event (median time to appearance 56 days). Time dependent covariate analysis (HR [95% CI]) identified baseline performance status (2.86 [1.75 to 4.55], p<0.001), BCLC (1.69 [1.18 to 2.50], p = 0.005), and dermatologic adverse event requiring dose adjustment within the first 60 days (0.58 [0.36 to 0.92], p = 0.022) as independent predictors of better outcome. Other early adverse events did not have an impact in outcome. The predictive value of dermatologic adverse events for survival was confirmed by the landmark analysis (p = 0.0270). CONCLUSIONS: Development of dermatologic adverse events within 60 days of sorafenib initiation is associated with better survival. Therefore, this should not to be taken as a negative event and discourage treatment maintenance. Likewise, second line clinical trials should be designed and/or evaluated considering this information to avoid significant bias.
Authors: R Diaz-Beveridge; G Bruixola; D Lorente; J Caballero; E Rodrigo; Á Segura; D Akhoundova; A Giménez; J Aparicio Journal: Clin Transl Oncol Date: 2017-08-11 Impact factor: 3.405
Authors: Li Gong; Marilyn M Giacomini; Craig Giacomini; Michael L Maitland; Russ B Altman; Teri E Klein Journal: Pharmacogenet Genomics Date: 2017-06 Impact factor: 2.089