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FROM THE LITERATURE
HEPATOCELLULAR CARCINOMA:
Improved Survival Seen In Advanced Disease with Sorafenib
The incidence of HCC is increasing in the U.S. and Europe, and it is the third highest
cause of cancer-related death globally, behind only lung and stomach cancers. No
systemic therapy has improved survival in patients with advanced HCC. A preliminary
study suggested that sorafenib (Nexavar), an oral multikinase inhibitor of the vascular
endothelial growth factor receptor (VEGFR), the platelet-derived growth factor receptor
β (PDGFR-β), and Raf may be effective in HCC. Results of this uncontrolled phase
II trial of a single-agent sorafenib demonstrated a median OS of 9.2 months and
a median time to progression (TTP) of 5.5 months.
On the basis of these data, investigators conducted a large (602 patient) phase
III, randomized, double blind, placebo-controlled trial to assess the efficacy and
safety of sorafenib in patients with advanced HCC who had not received previous
systemic treatment. Patients received either sorafenib 400 mg PO twice daily or
placebo. Primary outcomes were OS and the time to symptomatic progression. Secondary
outcomes were time to radiologic progression and safety.
At the second planned interim analysis, 321 deaths had occurred, and the study was
stopped. Median OS was 10.7 months in the sorafenib group and 7.9 months in placebo
patients (HR in sorafenib group, 0.69; p<0.001). There was no significant difference
between the two groups in the median time to symptomatic progression (4.1 months
vs. 4.9 months; p=0.77). The median time to radiologic progression was 5.5 months
in the sorafenib group and 2.8 months in the placebo group (p<0.001). Seven patients
in the sorafenib group (2%) and two patients in the placebo group (1%) had a partial
response; no patients had a complete response. Diarrhea, weight loss, hand-foot
skin reaction, and hypophosphatemia were more frequent in the sorafenib group.
Conclusions/Summary:
- This study showed that sorafenib prolonged median survival and the
time to progression by nearly 3 months in patients with advanced HCC.
- Future studies are warranted to evaluate sorafenib as an adjuvant
therapy after curative or locoregional therapies.
- Studies are needed to evaluate sorafenib in
combination with other molecular targeted therapies.
Llovet JM, Ricci S, Mazzaferro V, et al. Sorafenib in Advanced Hepatocellular Carcinoma.
N Engl J Med. 2008;378-390.
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