Sorafenib For Advanced Hepatocellular Carcinoma Research Articles

The emerging therapies are reshaping the first-line treatment for advanced hepatocellular carcinoma: a systematic review and network meta-analysis.

Given the superior performance of various therapies over sorafenib in advanced hepatocellular carcinoma (HCC) and the absence of direct comparisons, it is crucial to explore the efficacy of these treatments in phase III randomized clinical trials. The goal is to identify which patients are most likely to benefit significantly from these emerging therapies, contributing to more personalized and informed clinical decision-making. Systematic review and network meta-analysis. PubMed, Embase, ClinicalTrials.gov, and international conference databases have been searched from 1 January 2010 to 1 December 2023. After screening, 17 phase III trials encompassing 18 treatments were included. In the whole-population network meta-analysis, the newly first-line tremelimumab plus durvalumab (Tre + Du) was found to be comparable with atezolizumab plus bevacizumab (Atezo + Beva) in providing the best overall survival (OS) benefit [hazard ratio (HR) 1.35, 95% confidence interval (CI): 0.93-1.92]. Concerning OS benefits, sintilimab plus bevacizumab biosimilar (Sint + Beva), camrelizumab plus rivoceranib (Camre + Rivo), and lenvatinib plus pembrolizumab (Lenva + Pemb) appear to exhibit similar effects to Tre + Du and Atezo + Beva. In the context of progression-free survival, Atezo + Beva seemed to outperform Tre + Du (HR: 0.66 CI: 0.49-0.87), while the effects are comparable to Sint + Beva, Camre + Rivo, and Lenva + Pemb. Upon comparison between Asia-Pacific and non-Asia-Pacific cohorts, as well as between hepatitis B virus (HBV)-infected and non-HBV-infected populations, immune checkpoint inhibitor (ICI)-based treatments seemed to exhibit heightened efficacy in the Asia-Pacific group and among individuals with HBV infection. However, combined ICI-based therapies did not show more effectiveness than molecular-targeted drugs in patients without macrovascular invasion and/or extrahepatic spread. As for grades 3-5 adverse events, combined therapies showed comparable safety to sorafenib and lenvatinib. Compared with sorafenib and lenvatinib, combination therapies based on ICIs significantly improved the prognosis of advanced HCC and demonstrated similar safety. At the same time, the optimal treatment approach should be tailored to individual patient characteristics, such as etiology, tumor staging, and serum alpha-fetoprotein levels. With lower incidence rates of treatment-related adverse events and non-inferior efficacy compared to sorafenib, ICI monotherapies should be prioritized as a first-line treatment approach for patients who are not suitable candidates for ICI-combined therapies. PROSPERO, CRD42022288172.

Sorafenib Plus Hepatic Arterial Infusion Chemotherapy in Advanced Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

This meta-analysis aimed to determine whether sorafenib combined with hepatic arterial infusion chemotherapy is beneficial for advanced hepatocellular carcinoma. We searched PubMed, Cochrane Library, and Embase to identify comparative studies evaluating sorafenib plus hepatic arterial infusion chemotherapy versus sorafenib for advanced hepatocellular carcinoma. Overall survival, progression-free survival, objective response rate, rate of progressive disease, and adverse events were evaluated. This meta-analysis included 5 randomized controlled trials (690 patients). Pooled estimates showed that compared with sorafenib, sorafenib plus hepatic arterial infusion chemotherapy was associated with higher overall survival (hazard ratio = 0.52, 95% CI: 0.28-0.95, P = .03), progressionfree survival (hazard ratio = 0.57, 95% CI: 0.33-0.98, P = .04), objective response rate (risk ratio = 3.84, 95% CI: 1.23-12.05, P = .02), as well as higher rates of neutropenia (risk ratio = 7.90, 95% CI: 3.0-20.78, P < .0001) and thrombocytopenia (risk ratio = 2.73, 95% CI: 1.70- 4.36, P < .0001), but had no significant influence for rate of progressive disease (risk ratio = 0.76, 95% CI: 0.43-1.37, P = .37). Sorafenib plus hepatic arterial infusion chemotherapy improved overall survival, progression-free survival, and objective response rate, but it had no effect on the rate of progressive disease. Combination therapy has a survival benefit for advanced hepatocellular carcinoma patients, and adverse events can be accepted. However, more large-scale randomized controlled trials are needed for further investigation.

Efficacy of Sodium Alginate Microsphere Interventional Embolization Combined with Sorafenib in Advanced Hepatocellular Carcinoma

To explore the efficacy of sodium alginate microsphere (SAM) transcatheter arterial chemoembolization (TACE) combined with sorafenib in liver cancer (LC), 118 patients with advanced LC were enrolled in the study. Patients were randomized into c-TACE and SAM-TACE groups; in addition to TACE, the SAM-TACE group was treated with SAM and oral sorafenib. The physical properties and cytotoxicity of SAM were investigated in vitro. Liver function, tumor markers, the extent of solid tumor remission, adverse events, and survival rates were compared between the two groups during a 2-year follow-up period. The diameter of SAM was approximately 180–250 μm and the swelling rate of the microspheres was good, especially at pH 7.4. SAMs did not reduce 3T3-L1 and ECV-304 cell activities and was biocompatible. SAM-TACE was effective in protecting liver function in patients and, when combined with sorafenib, reduced tumor marker levels and cancer volumes, resulting in improved patient survival rates. SAM-TACE combined with sorafenib did not increase the rate of adverse reactions. Therefore, SAM-TACE combined with sorafenib has great potential in the treatment of advanced LC.

The ROWAN study: Safety and efficacy of transarterial radioembolization with Y-90 glass microspheres and the STRIDE regimen in hepatocellular carcinoma.

TPS622 Background: In patients with early and intermediate hepatocellular carcinoma (HCC) who are ineligible for resection, thermal ablation, or liver transplant, transarterial radioembolization (TARE) with yttrium-90 glass microspheres has shown superior efficacy compared to transarterial chemoembolization; a subset of patients progress despite effective local therapy. Immunotherapy using the single tremelimumab regular interval durvalumab (STRIDE) regimen has demonstrated superior overall survival to sorafenib in advanced HCC. Recent work showed that TARE upregulates both the innate and adaptive immune systems. The possibility for TARE and STRIDE to have additive or synergistic effects when combined is of current scientific and clinical interest. The primary objective of the Phase II ROWAN Study is to assess the objective response rate and durability of local tumor control with TARE followed by STRIDE vs. TARE alone. Methods: ROWAN is a global, open-label, prospective, multicenter randomized controlled trial comparing treatment with TARE using glass microspheres followed by the STRIDE regimen (a single dose of 300 mg tremelimumab combined with 1500 mg monthly dose of durvalumab for 18 months) to TARE alone in HCC. ROWAN will include 150 patients across approximately 20 study sites in North America and Europe. Key inclusion criteria: HCC, diagnosed by radiographic imaging or histology; ineligible for or declined liver resection, thermal ablation, or transplantation; Child-Pugh A; ECOG 0; life expectancy ≥6 months; treatment naïve; unilobar tumor; measurable by mRECIST; tumor volume ≤25% of whole liver volume; and untreated future liver remnant volume ≥30% of whole liver volume. Key exclusion criteria: extrahepatic metastases; shunt fraction with a lung dose of &gt;30 Gy; macrovascular invasion; infiltrative disease not evaluable by mRECIST; history of any organ allograph; autoimmune or inflammatory disorder; current use of immunosuppressive medication; history of malignancy other than HCC within past 3 years; and active infection. Patients will be randomized in a 1:1 ratio to two study arms (TARE followed by STRIDE or TARE alone) using two stratification factors (TARE treatment goal [ablative vs. non-ablative] and alpha fetoprotein level [&gt;400 vs. ≤400 ng/mL]). Tumor and blood samples will be collected for correlative studies. Co-primary efficacy endpoints are objective response rate and duration of response (localized mRECIST). The primary safety endpoint is the number of adverse events (AEs) and serious AEs. Interim statistical analyses will be conducted after 25 patients have been randomized to each arm and completed the second imaging assessment 6 months post-randomization; final analysis will be after the last evaluable patient has completed the 18 months follow-up visit post-randomization or discontinued treatment. Clinical trial information: 05063565 .

Survival Trends in Sorafenib for Advanced Hepatocellular Carcinoma: A Reconstructed Individual Patient Data Meta-Analysis of Randomized Trials

Background: Emerging data suggest that outcomes for advanced hepatocellular carcinoma (HCC) treated with sorafenib may have improved over time. We aimed to provide robust, time-to-event estimates of survival outcomes for sorafenib in advanced HCC. Summary: In this systematic review and individual patient data meta-analysis of randomized-controlled trials (RCTs), we searched MEDLINE and Embase from inception till September 2022 for RCTs that provided data for overall survival (OS) and progression-free survival (PFS) for sorafenib monotherapy as first-line systemic therapy for advanced HCC. We performed a pooled analysis using reconstructed individual participant data from published Kaplan-Meier curves to obtain robust estimates for OS and PFS. Of 1,599 articles identified, 29 studies (5,525 patients) met the inclusion criteria. Overall, the median OS was 10.4 (95% CI: 9.6–11.4) months. Median OS increased over time, from 9.8 (95% CI: 8.8–10.7) months in studies before 2015 to 13.4 (95% CI: 11.03–15.24) months in studies from 2015 onwards (p < 0.001). OS did not differ by trial phase, geographical region, or study design. The overall median PFS was 4.4 (95% CI: 3.9–4.8) months, but PFS did not improve over time. Sensitivity analysis of studies from 2015 and onwards to account for the introduction of direct-acting antivirals determined that hepatitis C virus was associated with reduced mortality (p < 0.001). There was minimal heterogeneity in the estimates for OS (all I² ≤ 33). Key Messages: Survival outcomes for sorafenib in advanced HCC have improved over time. These data have important implications for clinical trial design.

Issue on combined locoregional and systemic treatment for hepatocellular carcinoma

Treatment for hepatocellular carcinoma (HCC) has been challenging as most patients present with late, advanced disease, where curative options are limited. For years, locoregional therapy (LRT) has been the first-line therapy for intermediate-stage HCC and sorafenib for advanced HCC. However, these treatments are often palliative since they are plagued by tumor recurrence or progression. Therefore, there is growing interest in combined therapy to utilize their respective strengths to produce synergistic effects. This review outlines past and current research on the efficacy and safety of combined LRT and systemic therapy.

Synergistic antitumor activity of sorafenib and MG149 in hepatocellular carcinoma cells

Advanced hepatocellular carcinoma (HCC) is among the most challenging cancers to overcome, and there is a need for better therapeutic strategies. Among the different cancer drugs that have been used in clinics, sorafenib is considered the standard first-line drug for advanced HCC. Here, to identify a chemical compound displaying a synergistic effect with sorafenib in HCC, we screened a focused chemical library and found that MG149, a histone acetyltransferase inhibitor targeting the MYST family, exhibited the most synergistic anticancer effect with sorafenib on HCC cells. The combination of sorafenib and MG149 exerted a synergistic anti-proliferation effect on HCC cells by inducing apoptotic cell death. We revealed that cotreatment with sorafenib and MG149 aggravated endoplasmic reticulum (ER) stress to promote the death of HCC cells rather than adaptive cell survival. In addition, combined treatment with sorafenib and MG149 significantly increased the intracellular levels of unfolded proteins and reactive oxygen species, which upregulated ER stress. Collectively, these results suggest that MG149 has the potential to improve the efficacy of sorafenib in advanced HCC via the upregulation of cytotoxic ER stress. [BMB Reports 2022; 55(10): 506-511].

Hepatectomy versus sorafenib for advanced hepatocellular carcinoma with macroscopic portal vein tumor thrombus: A bi-institutional propensity-matched cohort study.

Sorafenib was previously considered a first-line treatment for hepatocellular carcinoma (HCC) patients with macroscopic portal vein tumor thrombus (PVTT). This case-matched analysis was performed to evaluate the best first-line treatment for HCC in patients with macroscopic PVTT. The HCC patients with Vp2 (PVTT invaded into a second-order portal branch), Vp3 (first-order portal branch), and Vp4 (main trunk or contralateral portal vein) PVTT who underwent hepatectomy and those treated with sorafenib were included. Treatment results were compared between the two modalities for each PVTT category, and a propensity analysis was performed for patients with Vp3 and Vp4 (Vp3/4). The median survival times (MSTs) of patients with Vp2, Vp3, and Vp4 PVTT who underwent hepatectomy were 21.4, 13.6, and 14.9months, respectively; the MSTs for those with Vp2, Vp3, and Vp4 PVTT who received sorafenib treatment were 6.9, 5.5, and 3.6months, respectively, with a significant difference. In a propensity-matched cohort of patients with Vp3/4 PVTT (36 patients in each), the MST of patients who underwent hepatectomy (15.1months) was significantly better than the patients treated with sorafenib (4.5months). Hepatectomy can be associated with prolonged survival in HCC patients with macroscopic PVTT.

Expanding Sorafenib Treatment for Hepatocellular Carcinoma Beyond Barcelona Clinic Liver Cancer Stage C Patients: A National Study

Background/Aim: The reimbursement criteria of sorafenib for advanced hepatocellular carcinoma (HCC) were expanded in 2016 by Taiwan’s National Health Insurance (NHI) to include patients without macrovascular invasion or extrahepatic spread. This study explored sorafenib treatment outcomes before and after this expansion. Patients and Methods: The NHI database was searched for patients who initiated sorafenib treatment between January 1, 2013, and December 31, 2017. Clinical variables were retrieved from the Taiwan Cancer Registry database. Overall survival (OS) and time to treatment discontinuation (TTD) were calculated as the times from the first sorafenib prescription date until death and the final prescription date, respectively. Results: A total of 13,862 patients were included. The median age was 64 years, 78.1% of patients were male. Approximately a quarter of patients (25.1%) received sorafenib after the criteria expansion and exhibited significantly longer OS (median 7.9 vs. 6.6 months, p&lt;0.001) and TTD (median 3.0 vs. 2.6 months, p=0.003) compared with patients who started before. These results were verified in patients with available data regarding clinical prognostic factors (n=9,378, 67.7% of the entire study population). In the multivariate analysis, sorafenib prescription after criteria expansion remained an independent predictor of longer OS [hazard ratio (HR)=0.87, p&lt;0.001] and TTD (HR=0.93, p=0.004). In the subgroup analysis, these trends were consistently observed across different patient subgroups. Conclusion: Patients with HCC who received sorafenib treatment after the reimbursement criteria expansion exhibited longer OS and TTD.

Cabozantinib plus atezolizumab in advanced hepatocellular carcinoma and the role of adjuvant antiviral therapy.

The treatment landscape for advanced hepatocellular carcinoma has changed greatly with the introduction of immune checkpoint inhibitors in addition to novel molecularly targeted agents such as anti-PD-1, anti-PD-L1, and anti-VEGF agents. 1 Llovet JM Castet F Heikenwalder M et al. Immunotherapies for hepatocellular carcinoma. Nat Rev Clin Oncol. 2022; 19: 151-172 Crossref PubMed Scopus (139) Google Scholar In phase 3 studies, anti-PD-1 and anti-PD-L1 in combination with anti-VEGF or anti-CTLA4 therapies have shown significantly better outcomes as first-line therapies compared with sorafenib. 2 Finn RS Qin S Ikeda M et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020; 382: 1894-1905 Crossref PubMed Scopus (2022) Google Scholar , 3 Ren Z Xu J Bai Y et al. Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study. Lancet Oncol. 2021; 22: 977-990 Summary Full Text Full Text PDF PubMed Scopus (153) Google Scholar , 4 Abou-Alfa GK Chan SL Kudo M et al. Phase 3 randomized, open-label, multicenter study of tremelimumab (T) and durvalumab (D) as first-line therapy in patients (pts) with unresectable hepatocellular carcinoma (uHCC): HIMALAYA. Proc Am Soc Clin Oncol. 2022; 40 (abstr).: 379 Crossref Google Scholar Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312): a multicentre, open-label, randomised, phase 3 trialCabozantinib plus atezolizumab might be a treatment option for select patients with advanced hepatocellular carcinoma, but additional studies are needed. Full-Text PDF Open Access

Efficacy and safety of radiotherapy plus anti-PD1 versus transcatheter arterial chemoembolization plus sorafenib for advanced hepatocellular carcinoma: a real-world study

BackgroundThe combination of transcatheter arterial chemoembolization (TACE) plus sorafenib prolonged progression-free survival (PFS) and overall survival (OS) than sorafenib or TACE monotherapy for patients with hepatocellular carcinoma (HCC). This study assessed the efficacy and safety of radiotherapy (RT) plus monoclonal antibody against programmed cell death 1 (anti-PD1) versus TACE plus sorafenib for patients with advanced HCC.MethodsPatients with advanced HCC who treated with RT plus anti-PD1 and TACE plus sorafenib were enrolled. Objective response rate (ORR), PFS, disease control rate (DCR) and OS were calculated to assess the antitumor response and the treatment-related adverse events to the safety.ResultsBetween January 2018 to March 2021, 37 patients underwent RT plus anti-PD1 and 41 patients underwent TACE plus sorafenib. The baseline characteristics between the two groups were comparable. The ORR and DCR were significantly higher in the RT + PD1 group than the TACE plus sorafenib group according to RECIST 1.1 (54.05% vs. 12.20%, P < 0.001; 70.27% vs. 46.37%, P = 0.041; respectively) and according to mRECIST (56.76% vs. 31.71%, P = 0.039; 70.27% vs. 46.37%, P = 0.041; respectively). RT plus anti-PD1 provided significantly better PFS (HR, 0.51; 95% CI 0.30–0.86; P = 0.017) than TACE plus sorafenib. Moreover, patients with RT plus anti-PD1 had significantly higher 3-, 6-, and 9-month OS rates than those with TACE plus sorafenib(97.3% vs. 92.30%, P < 0.001; 91.89% vs. 68.60%, P < 0.001; 75.5% vs. 60.60%, P < 0.001; respectively). The median OS was more favorable 17.4 months for the RT + PD1 group and 11.9 months for the TACE plus sorafenib group. No treatment-related death was observed. Grade 3 or more treatment-related adverse events (TRAEs) occurred significantly less in patients in the RT + PD1 group than the TACE plus sorafenib group (29.7% vs. 75.6%, P < 0.001), and all TRAEs were manageable.ConclusionsIn this real-world study, RT plus anti-PD1 showed significantly promising efficacy and manageable safety than TACE plus sorafenib in patients with advanced HCC. Toxicities were manageable, with no unexpected safety signals. The study provides evidence on a new therapeutic method in the treatment of advanced HCC.

Efficacy and safety of low-dose apatinib in advanced hepatocellular carcinoma.

4104 Background: Apatinib, a tyrosine kinase inhibitor, has shown promising effects on advanced hepatocellular carcinoma (HCC) recently. However, studies on its efficacy and safety are limited with controversial findings. Therefore, this study aimed to reveal the efficacy and safety of low-dose apatinib for the treatment of advanced HCC in the real world. Methods: Between January 2017 and August 2020, 178 patients with advanced HCC treated with apatinib at three different institutions were included for the present study. 174 patients received oral apatinib 250 mg daily and 4 received 500 mg daily until disease progression. 25 and 103 patients were also treated with immunotherapy and transcatheter arterial chemoembolization (TACE) at least once, respectively. Tumor response and adverse reactions were evaluated according to RECIST 1.1 and CTCAE 5.0 respectively. Survival curves were analyzed using the Kaplan-Meier method. Cox proportional hazards model was used to determine the prognostic value of variables in a univariate and multivariate setting. Results: During the 24-month follow-up period, 0 (0%), 28 (15.73%), 103 (57.87%) and 47 (26.40%) patients achieved a compete response (CR), partial response (PR), stable disease (SD), and progressive disease (PR), respectively. The overall response rate (ORR) and disease control rate (DCR) were 15.73% and 73.60% respectively. Interestingly, among the 28 patients with PR, 27 received apatinib as the first or second line treatment and 21 received immunotherapy or TACE as a combined treatment, indicating early application of apatinib and combination treatment could provide better efficacy. Kaplan-Meier analysis revealed the median overall survival (OS) and progressive-free survival (PFS) were 16.0 and 7.0 months respectively, which are significantly higher than previously reported survival of sorafenib in advanced HCC. Univariate Cox analysis indicated medication lines, distant metastasis, aplpha fetoprotein (AFP) level, portal vein tumor thrombus (PVTT) and combination therapy significantly affected OS and PFS. Multivariate Cox analysis confirmed third-line treatment (HR = 3.21; 95%CI = 1.54–6.68; p= 0.002), and PVTT (HR = 1.75; 95%CI = 1.13–2.70; p= 0.011) were independently associated with worse PFS. In contrast, apatinib combined with immunotherapy (HR = 0.52; 95%CI = 0.32–0.83; p= 0.008) or TACE (HR = 0.27; 95%CI = 0.18–0.40; p&lt; 0.001) were independently associated with better PFS. Similar findings were also present on OS. The most common treatment-related adverse events were hypertension (29.21%), fatigue (16.85%), hand and foot syndrome (16.29%), vomiting (14.04%), liver dysfunction (6.18%), and proteinuria (6.74%). No severe (grade ≥3) adverse events were observed. Conclusions: Low-dose apatinib is able to provide effective and safe treatment for advanced HCC. Early application of apatinib and combination treatment could provide even better efficacy.

Expanding the immunotherapy roadmap for hepatocellular carcinoma.

In a recent Lancet Oncology article, Yau etal. report the CheckMate 459 trial results. This is the first phase III trial comparing the single-agent anti-programmed death protein 1 (PD-1) therapy nivolumab to the tyrosine kinase inhibitor sorafenib for treatment-naive patients with advanced hepatocellular carcinoma.

Anti-PD-1 combined sorafenib versus anti-PD-1 alone in the treatment of advanced hepatocellular cell carcinoma: a propensity score-matching study

BackgroundVascular endothelial growth factor (VEGF) plays a role in the tumor microenvironment. Sorafenib, which inhibits the VEGF pathway, has an immune-modulation function but lacks substantial clinical data. This study aims to explore the efficacy of anti-PD-1 combined sorafenib in advanced hepatocellular carcinoma (HCC).MethodsHCC patients who underwent anti-PD-1 treatment at Taipei Veterans General Hospital (Taipei, Taiwan) between January 2016 and February 2019 were reviewed. The efficacy was compared between groups after propensity-score matching.ResultsThere were 173 HCC patients receiving anti-PD-1. After excluding unsuitable cases, 140 patients were analyzed, of which 58 received combination therapy and 82 received anti-PD-1 alone. The combination therapy had a trend of higher CR rate (8.6% vs. 4.9%, ns.), ORR (22.4% vs. 19.5%, ns.) and significantly higher DCR (69.0% vs. 37.8%, p < 0.05) comparing to anti-PD-1 alone. After matching, combination group achieved longer progression-free survival (3.87 vs. 2.43 months, p < 0.05) and overall survival (not reached vs. 7.17 months, p < 0.05) than anti-PD-1 alone, without higher grade 3/4 AE (10.3% vs. 7.1%, p = 0.73). The tumor response varied among different metastatic sites, with high responses in adrenal glands, peritoneum and lungs. The more AFP declined (> 10, > 50 and > 66%), the higher the ORR (70, 80 and 92%) and CR rates (30, 35 and 58%) were achieved at day 28.ConclusionsThis is the first study to demonstrate the combination of anti-PD-1 and sorafenib had better efficacy and survival benefit. A prospective randomized study is needed to confirm this finding.

Nivolumab and sorafenib in hepatocellular carcinoma: lessons from the CheckMate 459 study.

The increasing number of new options in each line of systemic treatment for hepatocellular carcinoma is associated with the challenge of how to extrapolate the clinical trials results into clinical practice. 1 Bruix J Chan SL Galle PR Rimassa L Sangro B Systemic treatment of hepatocellular carcinoma: an EASL position paper. J Hepatol. 2021; 75: 960-974 Summary Full Text Full Text PDF PubMed Scopus (49) Google Scholar The design of the multicentre, phase 3 CheckMate 459 trial, comparing nivolumab with sorafenib in patients with advanced hepatocellular carcinoma, was precise and robust, but it produced negative results, with no differences in overall survival (primary outcome; p=0·075) or progression-free survival. 2 Yau T Park J-W Finn RS et al. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial. Lancet Oncol. 2021; (published online Dec 13.)https://doi.org/10.1016/S1470-2045(21)00604-5 Summary Full Text Full Text PDF Google Scholar The authors suggest that these negative results could derive from the high proportion of patients treated with sorafenib who received immuno-oncology agents after discontinuing the study drug. Any further hypothesis to explain the results would be speculation. However, the CheckMate 459 study has some lessons that can be readily identified by the scientific community. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trialFirst-line nivolumab treatment did not significantly improve overall survival compared with sorafenib, but clinical activity and a favourable safety profile were observed in patients with advanced hepatocellular carcinoma. Thus, nivolumab might be considered a therapeutic option for patients in whom tyrosine kinase inhibitors and antiangiogenic drugs are contraindicated or have substantial risks. Full-Text PDF

HEPANOVA: Final Efficacy and Safety Results from a Phase 2 Study of Tumor Treating Fields (TTFields, 150 kHz) Concomitant with Sorafenib in Advanced Hepatocellular Carcinoma (HCC)

Introduction: TTFields are an anti-mitotic, regional therapy delivering non-invasive, low-intensity, alternating electric fields to a tumor using a portable medical device. TTFields are FDA-approved for treatment of glioblastoma and malignant pleural mesothelioma. In vitro and in vivo TTFields reduced HCC cell lines’ proliferative potential. If loco-regional treatment fails, most HCC patients are treated with best supportive care. Sorafenib is National Comprehensive Cancer category 1 treatment option for HCC patients with Child-Turcotte-Pugh class A.

P-285 Treatment outcomes with sorafenib in advanced hepatocellular carcinoma: A single-center retrospective study

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death globally. Sorafenib, an oral multikinase inhibitor, was the first to show improvement in the treatment of patients with advanced HCC. Until recently, it was the standard of care in the first-line treatment of advanced disease for more than a decade. Here, we present our real-world data on the treatment of advanced HCC with sorafenib.

O-16 HEPANOVA: Final efficacy and safety results from a phase 2 study of Tumor Treating Fields (TTFields, 150 kHz) concomitant with sorafenib in advanced hepatocellular carcinoma

Tumor Treating Fields (TTFields) are an anti-mitotic, regional treatment modality, utilizing low intensity alternating electric fields delivered non-invasively to the tumor using a portable medical device. TTFields are approved by the FDA for the treatment of glioblastoma and malignant pleural mesothelioma. In vitro and in vivo TTFields at 150 kHz reduced the proliferative potential of hepatocelluar carcinoma (HCC) cell lines. In patients with Barcelona clinic liver cancer (BCLC) stage C or stage B following failure of loco-regional treatments, systemic therapies are the standard of care in eligible patients.

Sorafenib is associated with a reduced rate of tumour growth and liver function deterioration in HCV-induced hepatocellular carcinoma

Sorafenib has been the standard of care for patients with advanced hepatocellular carcinoma and although immunotherapeutic approaches are now challenging this position, it retains an advantage in HCV-seropositive patients. We aimed to quantify the rate of tumour progression in patients receiving sorafenib and relate this figure to survival, both overall, and according to viral status. Using serial data from an international clinical trial we applied a joint model to combine survival and progression over time in order to estimate the rate of tumour growth as assessed by tumour burden and serum alpha-fetoprotein, and the impact of treatment on liver function. High tumour burden at baseline was associated with an increased risk of death. In patients still alive at the end of the study, the progression in relation to tumour burden was very low compared to those who died within the study. Overall, the change in mean tumour burden was 0.12mm per day or an absolute growth rate of 3.6mm/month. Median doubling time was 665 days. For those who progressed above 0.12mm per day or the 12% rate, median survival was 234 days compared to 384 days if the rate was below 12%. Tumour growth rate and serum alpha-fetoprotein rise were significantly lower in those who were HCV seropositive as was the rate of decline in liver function. These results were replicated in 2 independent patient groups. Our analysis suggests that sorafenib treatment is associated with improved survival in patients with advanced hepatocellular carcinoma mainly by decreasing the rate of tumour growth and liver function deterioration among patients with HCV infection. Among patients receiving sorafenib for advanced hepatocellular carcinoma the rate of tumour growth (as assessed by changes in tumour size and the biomarker alpha-fetoprotein) and the deterioration of liver function is less in those who have the hepatitis C virus, than in those who do not.

Hepatic Arterial Infusion Chemotherapy of Oxaliplatin, Fluorouracil, and Leucovorin With or Without Sorafenib as Initial Treatment for Advanced Hepatocellular Carcinoma.

PurposeOur previous study showed that hepatic arterial infusion chemotherapy (HAIC) using oxaliplatin, fluorouracil, and leucovorin (FOLFOX) plus sorafenib provided a significant survival benefit over sorafenib for advanced hepatocellular carcinoma. However, it is unclear whether the survival benefit should be attributed to the synergism between HAIC and sorafenib or just HAIC alone. We aim to compare HAIC using FOLFOX plus sorafenib with HAIC alone in patients with advanced hepatocellular carcinoma.Materials and MethodsThis was a retrospective study including 225 eligible patients treated with HAIC using FOLFOX (HAIC alone group, n=126, oxaliplatin 85 mg/m², leucovorin 400 mg/m², fluorouracil bolus 400 mg/m² and 2400 mg/m² for 46 hours, every 3 weeks) alone or HAIC plus sorafenib (soraHAIC group, n=99, sorafenib 400 mg twice daily). Survival curves were calculated by the Kaplan-Meier method, and propensity-score matching was used to reduce bias.ResultsThe soraHAIC group showed a longer overall survival (12.9 [95% CI, 10.4-15.4] vs. 10.5 [95% CI, 9.5-11.5] months, HR=0.71 [95% CI, 0.53-0.96]; P=0.025), a better progression free survival (7.0 [95% CI, 5.3-8.8] vs. 5.3 [95% CI, 3.5-7.1] months, HR=0.76 [95% CI, 0.58-0.99]; P=0.046), and a higher disease control rate (RECIST 1.1: 74.8% vs. 61.1%, P=0.030) than the HAIC alone group. In multivariate analysis, soraHAIC was an independent favor factor for survival. In terms of the grade 3/4 adverse event, hand–foot skin reaction was more frequent in the soraHAIC group than the HAIC alone group. In the propensity-score matched cohorts (93 pairs), the overall survival, the progression free survival and disease control rates in the soraHAIC group were also better than those in the HAIC group (P<0.05).ConclusionHAIC plus sorafenib may improve overall survival and progression free survival compared with HAIC alone as initial treatment for advanced hepatocellular carcinoma.