title: Predictors of survival in patients with advanced hepatocellular carcinoma who permanently discontinued sorafenib.
abstract: Treatment with sorafenib of patients with advanced hepatocellular carcinoma is challenged by anticipated discontinuation due to tumor progression, liver decompensation, or adverse effects. While postprogression survival is clearly determined by the pattern of tumor progression, understanding the factors that drive prognosis in patients who discontinued sorafenib for any reason may help to improve patient management and second-line trial design. Patients consecutively admitted to three referral centers who were receiving best supportive care following permanent discontinuation of sorafenib for any reason were included. Postsorafenib survival (PSS) was calculated from the last day of treatment to death or last visit available. Two hundred and sixty patients were included in this prospective study, aged 67 years, 60% with hepatitis C, 51% Child-Pugh A, 83% performance status (PS) ≥1, 41% with macroscopic vascular invasion, and 38% with extrahepatic tumor spread. Overall, median PSS was 4.1 (3.3-4.9) months, resulting from 4.6 (3.3-5.7) months for 123 progressors, 7.3 (6.0-10.0) months in 77 with adverse effects, and 1.8 (1.6-2.4) months in 60 decompensated patients (P < 0.001). Postsorafenib survival was independently predicted by PS, prothrombin time, extrahepatic tumor spread, macrovascular invasion, and reason for discontinuation. Two hundred patients potentially eligible for second-line therapy had a PSS of 5.3 (4.6-7.1) months, which was dependent on reasons of discontinuation (P = 0.004), PS (P < 0.001), macrovascular invasion (P < 0.001), and extrahepatic metastases (P < 0.002).
  
  
  CONCLUSIONS
  Discontinuation due to adverse effects in the absence of macrovascular invasion, extrahepatic metastases, and deteriorated PS predicts the best PSS in compensated patients, thereby setting the stage for both improved patient counseling and selection for second-line therapy.
authors: A.M.&A. Migliavacca Center for Liver Disease, 1st Division of Gastroenterology, Fondazione IRCCS Ca' Granda Maggiore Hospital, University of Milan, Milan, Italy.
authors: Massimo
authors: M
authors: Iavarone
authors: Sezione di Gastroenterologia, DIBIMIS, University of Palermo, Palermo, Italy.
authors: Giuseppe
authors: G
authors: Cabibbo
authors: Institute of Internal Medicine, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
authors: Marco
authors: M
authors: Biolato
authors: A.M.&A. Migliavacca Center for Liver Disease, 1st Division of Gastroenterology, Fondazione IRCCS Ca' Granda Maggiore Hospital, University of Milan, Milan, Italy.
authors: Cristina
authors: C
authors: Della Corte
authors: Sezione di Gastroenterologia, DIBIMIS, University of Palermo, Palermo, Italy.
authors: Marcello
authors: M
authors: Maida
authors: University of Palermo, Palermo, Italy.
authors: Marco
authors: M
authors: Barbara
authors: Institute of Internal Medicine, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
authors: Michele
authors: M
authors: Basso
authors: A.M.&A. Migliavacca Center for Liver Disease, 1st Division of Gastroenterology, Fondazione IRCCS Ca' Granda Maggiore Hospital, University of Milan, Milan, Italy.
authors: Sara
authors: S
authors: Vavassori
authors: Sezione di Gastroenterologia, DIBIMIS, University of Palermo, Palermo, Italy.
authors: Antonio
authors: A
authors: Craxì
authors: Institute of Internal Medicine, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
authors: Antonio
authors: A
authors: Grieco
authors: Sezione di Gastroenterologia, DIBIMIS, University of Palermo, Palermo, Italy.
authors: Carlo
authors: C
authors: Cammà
authors: A.M.&A. Migliavacca Center for Liver Disease, 1st Division of Gastroenterology, Fondazione IRCCS Ca' Granda Maggiore Hospital, University of Milan, Milan, Italy.
authors: Massimo
authors: M
authors: Colombo
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007558:Italy; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018579:Patient Selection; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015203:Reproducibility of Results; D018570:Risk Assessment; D000077157:Sorafenib; D016019:Survival Analysis; D028761:Withholding Treatment / Q000706:statistics & numerical data*
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib