Early dermatologic adverse events predict better outcome in HCC patients treated with sorafenib.
OBJECTIVE
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.
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.
Maria
M
Reig
Biostatistics and Data Management Core Facility, IDIBAPS, Hospital Clínic Barcelona, Spain; Biostatistics Unit, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Ferran
F
Torres
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.
Carlos
C
Rodriguez-Lope
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.
Alejandro
A
Forner
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.
Neus
N
LLarch
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.
Jordi
J
Rimola
Barcelona Clinic Liver Cancer (BCLC) Group, Radiology Department, Hospital Clínic Barcelona, IDIBAPS, University of Barcelona, Barcelona, Spain.
Anna
A
Darnell
Biostatistics and Data Management Core Facility, IDIBAPS, Hospital Clínic Barcelona, Spain; Biostatistics Unit, School of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
José
J
Ríos
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.
Carmen
C
Ayuso
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.
Jordi
J
Bruix
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000009:adverse effects*; D011446:Prospective Studies; D012867:Skin / Q000187:drug effects*; D000077157:Sorafenib
D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
Clinical marker; Early adverse events; Hepatocellular carcinoma; Overall survival; Sorafenib