DERMATOLOGIC ADVERSE EVENTS WITHIN THE FIRST 60 DAYS OF SORAFENIB TREATMENT ARE ASSOCIATED WITH BETTER OVERALL SURVIVAL (OS) IN PATIENTS WITH HEPATOCELLULAR CARCINOMA (HCC)

Background: Sorafenib [Sor] improves the OS of patients with
advanced HCC. Currently, there are no clinical data or markers to
predict better survival. The majority of Sor adverse events (AEs)
[dermatologic, gastrointestinal or cardiovascular], appear within
the first 60 days of treatment and they may influence patients
management and outcome.
Aim: To analyze in a cohort of HCC patients treated with Sor the
association of dermatologic AEs emerging within the first 60 days
(AED60) with the outcome in terms of time to progression (TTP)
and OS.
Methods: We prospectively included patients Child–Pugh
A/B7 without ascites/encephalopathy, PS 0–1, and without
contraindication or risk for Sor. Follow-up included monthly clinical
and laboratory monitoring and tumor staging at week 4 and every
8 weeks.
Results: We included 147 patients [Oct. 2007-Jul. 2011] (97%
cirrhotic, 46% HCV+, 64yrs, 82% Child–Pugh A, PS 0 84%, BCLC-B 78,
BCLC-C 69. With a median follow up of 11.6 months and a treatment
duration (mTD) of 6.7 months, TTP and OS were 5.1 months
and 12.7 months, respectively. 79 patients presented AED60 and
37 patients needed Sor dose modification due to AED60. Median
TTP (6.3 vs. 2.7; p = 0.02) and OS (18.2 vs. 9.9; p < 0.001) were
significantly better in patients with AED60, while mTD was similar
[EAD60: 7.6 vs. noEAD60: 5.5; p=NS]. However, patients with EAD60
presented more dose modifications [3 vs. 2 (p = 0.006)]. Results
were similar when excluding the 8 patients that died during the
first 60 days. Other early AEs categories did not have an impact in
outcome. Baseline PS (p < 0.001), BCLC (p = 0.009) and EAD60 of any
grade (p = 0.04) were associated with better OS in the multivariate
analysis of the whole cohort. Nevertheless, when excluding early
deaths, the predictive value was restricted to EAD60 > grade I which
determines Sor dose modification (p = 0.03).
Conclusion: 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, 2nd line clinical trials
should be designed and/or evaluated considering this information
to avoid significant bias