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Currently, sorafenib is the standard of care for patients with hepatocellular carcinoma (HCC). Prior to the approval of sorafenib, there were no systemic agents for HCC. The multicenter, phase III, double-blind, placebo-controlled SHARP trial, explains Richard Finn, MD, was the pivotal trial designed to test the effects of sorafenib on overall survival and the time to symptomatic progression in HCC. In the trial, 602 patients with advanced HCC who had not received previous systemic treatment were randomized to receive either sorafenib or placebo.
Use of sorafenib resulted in a median overall survival of 10.7 months versus 7.9 months in the placebo group (HR, 0.69; 95% CI, 0.55-0.87; P <.001). Although there was no significant difference between the 2 groups in the median time to symptomatic progression (4.1 months vs 4.9 months, respectively; P = .77), median time to radiologic progression, a secondary endpoint, was 5.5 months with the sorafenib group versus 2.8 months with placebo (P <.001).
The challenge comes when treating a patient with sorafenib who does not fit the perfect paradigm of having well-compensated liver disease, as studied in the SHARP trial, notes Finn. Patients’ liver disease can continue to worsen even if sorafenib successfully controls progression. Outside of the Child-Pugh A population, sorafenib has not been shown to improve survival.
The type of patients more commonly seen in clinics may not be as healthy as those in the study, but there is a role for sorafenib to slow tumor progression, comments Finn. There may not be dramatic shrinkage of tumors in this group of patients, but more typically, sorafenib has led to stable disease or slowing of progression. For this group, who tend to be Child Pugh B patients, clinicians should be more attuned to the potential for side effects. Sorafenib has a very predictable toxicity profile, including GI toxicity, and hand-foot syndrome, which can be treated prophylactically using urea-based creams.
There may be differences in dose reduction and dose re-escalation practices, notes Robert Gish, MD, FAASLD. Some of these differences may be based on personal or professional experience with the medication, he explains. The package insert does not discuss dose re-escalation, although many clinicians are managing dosing modifications comfortably.