Efficacy of Sorafenib in Intermediate-Stage Hepatocellular Carcinoma Patients Refractory to Transarterial Chemoembolization

Abstract

Objective: We compared the benefits of sorafenib therapy with continued transarterial chemoembolization (TACE) in TACE-refractory patients with intermediate-stage hepatocellular carcinoma (HCC). Methods: This retrospective study reviewed intermediate-stage HCC patients who underwent the first TACE. Patients were defined as TACE-refractory and divided into two cohorts: (1) patients who switched from TACE to sorafenib and (2) those who continued TACE. We evaluated the patient overall survival (OS) and time to disease progression (TTDP; the time patients reached Child-Pugh C or developed advanced-stage HCC). Results: A total of 509 patients with HCC underwent TACE. Of 249 intermediate-stage HCC patients undergoing the first TACE, 122 were deemed refractory. At the time they were identified as refractory, 20 patients converted to sorafenib, whereas 36 patients continued TACE. We excluded patients with Child-Pugh scores of ≥8, those with advanced-stage HCC, those who had undergone hepatic arterial infusion chemotherapy or other systemic therapy, and those treated with best supportive care alone. The median TTDP and OS were 22.3 and 25.4 months, respectively, in the conversion group, and 7.7 and 11.5 months, respectively, in the continued group (p = 0.001 and p = 0.003, respectively). Conclusions: It is possible that sorafenib conversion might prolong OS and TTDP in TACE-refractory patients with intermediate-stage HCC.

The Overall Survival of Patients with Hepatocellular Carcinoma Correlates with the Newly Defined Time to Progression after Transarterial Chemoembolization

“…Another possible reason is that post-cTACE treatment might have been effective, thereby contributing to the long OS observed in some cases with a short TTTP. For example, the use of sorafenib to treat patients with TACErefractory disease and a short TTTP actually prolongs OS [9,10] . However, in general we found that OS correlated with TTTP in patients with B1 or B2 substage HCC.…”

“…Currently, sorafenib is the only treatment strategy available after failure of TACE [9,10] . However, in clinical practice, "progression" is not determined by development of a new small lesion, and switching from TACE to sorafenib or other therapies does not necessarily happen at this point.…”

Current status and future prospects of chemotherapy for advanced hepatocellular carcinoma

“…In the SHARP trial sub-analyses [14], the hazard ratio of sorafenib against placebo was best in BCLC intermediate stage. When Ogasawara et al [18] and Arizumi et al [19] retrospectively compared two groups that satisfied the definition of TACE refractory, one group that continued with TACE and another group that changed to sorafenib, they reported that the sorafenib group had a significantly longer survival period. Therefore, we consider it important to understand the optimal timing for switching to sorafenib.…”

Early sorafenib induction after transarterial chemoembolization for unresectable hepatocellular carcinoma: Can sorafenib after TACE improve loco‑regional control?

“…TACE is a palliative rather than curative treatment. It can be carried out repeatedly for unresectable HCC, but if the effect is judged to be poor, or TACE-refractory, introduction of sorafenib is considered (5,6). However, the safety and efficacy of early sorafenib induction after TACE has yet to be established.…”