Regorafenib as Second-Line Systemic Therapy May Change the Treatment Strategy and Management Paradigm for Hepatocellular Carcinoma

Prognostic Factors Associated with Postprogression Survival in Advanced Hepatocellular Carcinoma Patients Treated with Sorafenib Not Eligible for Second-Line Regorafenib Treatment

“…Thus, in patients refractory to so­ra­fenib, postprogression survival (PPS) is expected to improve by switching from sorafenib to regorafenib [2, 3]. However, not all patients who have confirmed radiological PD can switch to regorafenib therapy, because the efficacy and safety of regorafenib administration in patients who do not meet the eligibility criteria for the RESORCE trial have not been verified [4].…”

Cabozantinib as a Second-Line Agent in Advanced Hepatocellular Carcinoma

“…2). The trial design was not as sophisticated as that of the RESORCE trial [2, 20]. For example, vascular invasion and/or extrahepatic spread was included as a stratification factor, which may result in an unfavorable imbalance regarding patients with vascular invasion.…”

“…The RESORCE trial led to the inclusion of vascular invasion as an independent stratification factor and alpha-fetoprotein as a stratification factor in the design of trials of second-line drugs [21]. However, the CELESTIAL trial had a conventional design with few strategic elements (Table 6) and did not even exclude sorafenib-intolerant patients as in the RESORCE trial [2, 20, 21]. The only inclusion criteria regarding prior treatment were (a) prior sorafenib treatment, (b) progression following at least 1 prior systemic treatment for HCC, and (c) up to 2 prior systemic regimens for advanced HCC; the exact number of sorafenib-intolerant patients enrolled remains unclear.…”

Molecular Targeted Agents for Hepatocellular Carcinoma: Current Status and Future Perspectives

“…In fact, this actually happened in a clinical trial of brivanib as second-line therapy (Table 3) [13]. In the RESORCE trial, which reported a positive outcome, patients were stratified separately by vascular invasion and by extrahepatic spread [19]. …”

“…This analysis revealed that OS in the axitinib arm was much better than in the placebo arm when patients who discontinued therapy due to adverse events were excluded [22]. Taking this into consideration, clinical trials of second-line agents should enroll only those patients unresponsive to sorafenib, as was done in the RESORCE study [19]. …”