The safety and efficacy of transarterial chemoembolization combined with sorafenib and sorafenib mono-therapy in patients with BCLC stage B/C hepatocellular carcinoma

Abstract

BackgroundSorafenib and transarterial chemoembolization (TACE) are recommended therapies for advanced hepatocellular carcinoma (HCC), but their combined efficacy remains unclear.MethodsBetween August 2004 and November 2014, 104 patients with BCLC stage B/C HCC were enrolled at the Affiliated Tumor Hospital of Guangxi Medical University, China. Forty-eight patients were treated with sorafenib alone (sorafenib group) and 56 with TACE plus sorafenib (TACE + sorafenib group). Baseline demographic/clinical data were collected. The primary outcomes were median overall survival (OS) and progression-free survival (PFS). Secondary outcomes were overall response rate (ORR) and sorafenib-related adverse events (AEs). Baseline characteristics associated with disease prognosis were identified using multivariate Cox hazards regression.ResultsThe mean age of the 104 patients (94 males; 90.38%) was 49.02 ± 12.29 years. Of the baseline data, only albumin level (P = 0.028) and Child-Pugh class (P = 0.017) differed significantly between groups. Median OS did not differ significantly between the sorafenib and TACE + sorafenib groups (18.0 vs. 22.0 months, P = 0.223). Median PFS was significantly shorter in the sorafenib group than that in the TACE + sorafenib group (6.0 vs. 8.0 months, P = 0.004). Six months after treatments, the ORRs were similar between the sorafenib and TACE + sorafenib groups (12.50% vs. 18.75%, P = 0.425). The rates of grade III–IV adverse events in sorafenib and TACE + sorafenib groups were 29.2% vs. 23.2%, respectively. TACE plus sorafenib treatment (HR = 0.498, 95% CI = 0.278–0.892), no vascular invasion (HR = 0.354, 95% CI = 0.183–0.685) and Child-Pugh class A (HR = 0.308, 95% CI = 0.141–0.674) were significantly associated with better OS, while a larger tumor number was predictive of poorer OS (HR = 1.286, 95% CI = 1.031–1.604). TACE plus sorafenib treatment (HR = 0.461, 95% CI = 0.273–0.780) and no vascular invasion (HR = 0.557, 95% CI = 0.314–0.988) were significantly associated with better PFS.ConclusionsCompared with sorafenib alone, combining TACE with sorafenib might prolong survival and delay disease progression in patients with advanced HCC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3545-5) contains supplementary material, which is available to authorized users.

The combination therapy of transarterial chemoembolisation and sorafenib is the preferred palliative treatment for advanced hepatocellular carcinoma patients: a meta-analysis

“…Our result, that the OS of patients with advanced HCC treated with combination therapy was superior to that of those patients treated with sorafenib alone, maps to the conclusions of 4 retrospective studies [19,31,56,57] but is in contrast to a clinical trial by Zhang and colleagues in 2015 [43]. In this study, despite a numerically greater median OS in the combined-therapy group than in the sorafenib-alone group (7.3 months vs. 6.0 months), no difference was observed between the two groups (P = 0.924).…”

“…Our results mirror the findings from two metaanalyses in which both corroborate the improved tumour regression and disease control of patients with advanced HCC after combination therapy compared to TACE monotherapy [55,58]; however, the combined treatment may not be superior to TACE alone to increase the ORR and curtail the DPR in patients with early-to-intermediate HCC [59]. In this present analysis, we moreover demonstrate the better ORR in the combination therapy arm than that in the sorafenib-alone arm, but the conclusions of three key clinical trials in this context are contradictory [19,39,60]. One explanation is that one of them classified patients with advanced HCC into a BCLC-B stage group and a BCLC-C stage group and demonstrated that the superiority of combination therapy compared to sorafenib monotherapy was manifested only in the former group but not in the latter group, whereas the other studies did not implement this subgroup analysis.…”

Role of locoregional therapies in the wake of systemic therapy

“…A single-centre retrospective study in 104 patients with advanced HCC, with or without PVT, found that sorafenib combined with TACE was associated with improved OS compared to sorafenib alone (HR 0.498; 95% CI 0.278-0.892). 44 Similarly, in a retrospective study of 658 patients with advanced HCC, Ha et al compared treatment with sorafenib alone, c-TACE combined with sorafenib, and c-TACE followed by sorafenib. On subgroup analysis they identified that patients with portal invasion benefited significantly from the combination (median OS for sorafenib monotherapy 5.5 months; for c-TACE followed by sorafenib 14.0 months, p = 0.030; for the combination 25.7 months, p = 0.002).…”

Effectiveness of Particle Radiotherapy in Various Stages of Hepatocellular Carcinoma: A Pilot Study

“…Sorafenib or another chemotherapeutic was usually chosen for advanced-stage HCC (group C) with or without extrahepatic progression, but the local control rate was very low [26]. Regarding the effect of PRT on portal tumor thrombi and extrahepatic metastasis, the local tumor control rates were unexpectedly high in group C (Table 2).…”

“…Another study showed that 6 months after treatment for BCLC stage B/C HCCs, the overall response rate was 12.50% in the sorafenib monotherapy group and 18.75% in the TACE + sorafenib group [26]. When patients with early-stage HCC (groups A and B) could not undergo radical therapies because of comorbidities, they usually underwent a less curative therapy, such as TACE or possibly sorafenib-based chemotherapy.…”