Sorafenib shows favourable clinical efficacy, improved survival benefit in HCC
The addition of the multikinase inhibitor sorafenib to FOLFOX* or transarterial chemoembolization (TACE) demonstrated favourable clinical efficacy and improved survival outcomes in hepatocellular carcinoma (HCC), according to several studies presented at the ASCO Gastrointestinal Cancers Symposium 2018 (ASCO GI 2018).
A single-arm, phase II study on 40 individuals (median age 65 years, 85 percent male) with advanced HCC revealed a median time to progression (TTP) of 8.8 months (95 percent confidence interval [CI], 6.5–11.2), an overall response rate (ORR) of 18 percent, and a stable disease rate of 55 percent after administration of twice-daily sorafenib 400 mg followed by a concurrent modified FOLFOX regimen. [ASCO GI 2018, abstract 270]
“[Sorafenib plus FOLFOX] demonstrated encouraging clinical efficacy … for first-line treatment of advanced HCC,” said the researchers, adding that the findings outdid the results of the SHARP** trial which showed a median TTP of 5.5 months and an ORR of 2 percent with sorafenib use. [N Engl J Med 2008;359:378-390]
The researchers postulated that the prolonged TTP could be attributed to the low baseline plasma levels of s-VEGF# receptor 1, VEGF-C, and bFGF##.
The randomized phase II TACTICS### trial further underscored the potential of sorafenib in prolonging median TTP when added to TACE as opposed to receiving TACE alone in unresectable HCC (24.1 vs 13.5 months, hazard ratio [HR], 0.56, 95 percent CI, 0.38–0.83; p=0.004). [ASCO GI 2018, abstract 206]
Median progression-free survival (PFS; 25.2 vs 13.5 months, HR, 0.59, 95 percent CI, 0.41–0.87; p=0.006) and time to untreatable progression (26.7 vs 20.6 months, HR, 0.57, 95 percent CI, 0.35–0.92; p=0.02) were also significantly improved with TACE plus sorafenib vs TACE alone.
A retrospective study on 232 patients with advanced HCC (mean age 71 years, 77 percent male) also demonstrated favourable results with sorafenib use, with overall survival (OS) rates of 72.4 percent, 53.6 percent, and 41.9 percent at 6, 12, and 18 months, respectively. [ASCO GI 2018, abstract 497]
“Sorafenib is the only approved first-line agent … [for] advanced HCC … Therefore, it is very important to maintain sorafenib therapy until sorafenib resistance occurs,” said the researchers of the retrospective analysis.
Given the encouraging survival and safety profile observed with regorafenib, patients who progress after sorafenib could receive regorafenib as a second-line treatment, they added. [World J Clin Oncol 2017;8:203-213]
Taken together, these findings support the favourable clinical efficacy and survival benefit associated with sorafenib, given its potential in delaying disease progression by targeting key pathways in the pathogenesis of HCC. [N Engl J Med 2008;359:378-390]