TY - JOUR
T1 - Early dermatologic adverse events predict better outcome in HCC patients treated with sorafenib
AU - Reig, Maria
AU - Torres, Ferran
AU - Rodriguez-Lope, Carlos
AU - Forner, Alejandro
AU - Llarch, Neus
AU - Rimola, Jordi
AU - Darnell, Anna
AU - Ríos, José
AU - Ayuso, Carmen
AU - Bruix, Jordi
N1 - Funding Information:
This study has been supported by a grant from the Instituto de Salud Carlos III ( PI11/01830 ). CIBERehd is funded by Instituto de Salud Carlos III . Carlos Rodríguez de Lope is supported by a grant from the Instituto de Salud Carlos III ( FI09/00510 ). Maria Reig was partially supported by a grant from the University of Barcelona ( APIF RD63/2006 ).
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
KW - Clinical marker
KW - Early adverse events
KW - Hepatocellular carcinoma
KW - Overall survival
KW - Sorafenib
UR - http://www.scopus.com/inward/record.url?scp=84904751197&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2014.03.030
DO - 10.1016/j.jhep.2014.03.030
M3 - Article
C2 - 24703956
VL - 61
SP - 318
EP - 324
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 2
ER -