Sorafenib Era Research Articles

Outcomes of hepatocellular carcinoma patients treated in the lenvatinib and immunotherapy era (2018-2021) compared to the sorafenib era (2008-2018).

Lenvatinib (LEN) and atezolizumab + bevacizumab (A + B) have drastically changed the treatment paradigm for advanced hepatocellular carcinoma (HCC). Before these landmark trials, sorafenib (SOR) served as the standard first-line treatment for a decade. Our study aimed to assess the outcomes of HCC patients treated during the SOR era (2008-2018) in contrast to those in the post-SOR era (2018-2021), of which the predominant first-line treatments were LEN or A + B. Inclusion criteria of the study were all HCC patients in the Canadian province of Alberta who started first-line systemic therapy at cancer centers between 1 January 2008 and 31 December 2021. Survival outcomes, including overall survival (OS) and progression-free survival (PFS), along with clinician-assessed response rate (RR), were subject to retrospective analysis. Of 372 total patients, 230 received treatment in the SOR era and 142 in the post-SOR era. The demographic and clinical characteristics for the SOR era and post-SOR era groups are as follows, respectively: the median age was 63 and 64 years, 80% and 81% were male, and 24% and 11% were of East Asian ethnicity. Before receiving systemic treatment, 40% and 33% received TACE, 7% and 9% received TARE, and 3% and 14% received SBRT in the two eras, respectively. In the post-SOR era, patients received A + B (23%), LEN (51%), and SOR (23%) as first-line treatment. There was a statistically significant improvement in RR (15% vs. 26%; p = 0.02), median PFS (3.8 months vs. 7.9 months; p < 0.0001), and median OS (9.8 months vs. 17.0 months; p < 0.0001). In this retrospective multicenter real-world study, HCC patients treated in the post-SOR era, where LEN and A + B were commonly used first-line treatments, exhibited superior OS, PFS, and RR compared to patients treated in the SOR era. The findings of this study affirm the tangible progress achieved in the real world in enhancing outcomes for HCC patients through advancements in treatments over the past 15 years.

Outcomes of patients with hepatocellular carcinoma (HCC) treated in the lenvatinib (LEN) and immunotherapy era (2018-2021) compared to the sorafenib (SOR) era (2008-2018).

553 Background: SOR was the standard first-line treatment for HCC for about a decade until the approval of LEN. Subsequently, atezolizumab + bevacizumab (A+B) were shown to have superior efficacy outcomes. The aim of this study was to compare effectiveness outcomes of HCC patients treated in the SOR era compared to the post-SOR era, when most HCC patients received first-line LEN or A+B. Methods: All HCC patients who started first-line systemic therapy at cancer centres in the Canadian province of Alberta between January 1, 2008 and December 31, 2021 were included in this study. Overall survival (OS), progression-free survival (PFS), and clinician-assessed response rate (RR) were retrospectively analyzed. Since LEN was first available to patients in Canada in August 2018, patients who started first-line systemic therapy between January 2008 to July 2018 were classified as treated in the “SOR era”, while patients treated from August 2018 to December 2021 were classified as being treated in the “post-SOR era”. Results: Of 372 total patients included, 230 were treated in the SOR era and 142 in the post-SOR era. Demographic and clinical characteristics are as follows for the SOR era and post-SOR era groups, respectively: median age was 63 and 64 years, 80% and 81% were male, 24% and 11% were of East Asian ethnicity. Most patients were ECOG 0-1 (85% and 91%), Child-Pugh A (84% and 85%), and ALBI grade 1 or 2 (96% and 98%) prior starting first-line therapy. Most common causes of liver disease included excess alcohol use (24% and 30%), Hepatitis C (37% and 48%), and Hepatitis B (27% and 15%). Most patients had advanced (BCLC C) stage disease in both groups (91% and 87%). Prior to systemic treatment 40% and 33% received TACE, 7% and 9% received TARE, and 3% and 14% received SBRT respectively. See table for first-line treatments received and outcomes. Median treatment duration was 3.2 months and 4.8 months, and median follow-up time was 9.6 and 11.0 months for SOR era and post-SOR era, respectively. Conclusions: In this real-world multicenter retrospective study, patients treated in the post-SOR era, where LEN and A+B were the more common first-line treatments, had superior overall survival, first-line response rates and progression-free survival. This study confirms the real-world progress that has been made in improving outcomes of HCC patients through systemic treatment advancements over the last 15 years.[Table: see text]

Presentation and Outcomes of Hepatocellular Carcinoma in the Arabian Peninsula: A Review of a Single Institution Experience in the Sorafenib Era.

There is a growing evidence showing that there are geographic differences in hepatocellular carcinoma (HCC). Little is known about the characteristics of hepatocellular carcinoma in the Arabian Peninsula. The present study examines the presentation and outcomes of HCC in a single institution. A retrospective chart review of patients presented with advanced-stage HCC to Kuwait Cancer Control Center (KCCC) between 2008 and 2018 was conducted. Data collected included patients demographics, HCC risk factors, performance status, Child-Pugh score, pick up of sorafenib, and survival. About 111 cases were analyzed. The mean age of the cohort was 61.8 ± 11.4 years and 94 patients (84.7%) were males. HCV and diabetes were the most common risk factors for HCC and presented in 60 patients (54.1%) and 45 patients (40.5%), respectively. About 78 (70.3%) patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 at presentation. Only 29 (26.1%) patients presented with Child-Pugh class A, while 42 (40.4%) patients received sorafenib. The median overall survival was only 3 months. In our cohort, HCV and diabetes were the main risk factors for HCC. The majority of patients was not amenable to sorafenib treatment and carries a very poor prognosis.

Survival differences among patients with hepatocellular carcinoma based on the stage of disease and therapy received: pre and post sorafenib era.

The incidence of hepatocellular carcinoma (HCC) is increasing. Development of newer therapeutic modalities has changed the paradigm of HCC treatment in recent years. So, the aim of our study is to analyze the impact of these treatment modalities into the survival of HCC patients, based on the stage of HCC in real life practice. We analyzed the data from the SEER database: Incidence - SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2015 Sub (1973-2013 varying). Relative survival rates (RSRs) and hazard ratios (HRs) were measured for patients diagnosed with HCC between 2001 and 2013. Rates were compared between pre sorafenib [2001-2007] and post sorafenib [2008-2013] eras. A total of 50,088 patients (21,435 in pre sorafenib era and 28,653 in the post-sorafenib era) were included with HCC from SEER database. The median relative survival for the entire population was 14 months with 5-year RSR of 21.20%; 11 months for those diagnosed in 2001-2007 with 5-year RSR 19.30% and 17 months for those diagnosed in 2008-2013 with 5-year RSR 22.40% (P<0.01). This survival improvement was largely limited to HCC patients with single nodule (5-year RSR; 35.1% vs. 37.00% for pre and post sorafenib era respectively; P value <0.01) and multiple nodules without vascular invasion (5-year RSR; 19.90% vs. 22.60% for pre and post sorafenib era respectively; P value <0.01). RSR remained extremely poor with no significant improvement for advanced stage HCC who had vascular invasion (P=0.37) or distant metastasis (P=0.10), respectively for pre and post sorafenib era in each category. Survival improved since 2008, for HCC patients who received either no surgical intervention (P<0.01) or received tumor-directed therapy (P<0.01), however, it remained significantly poor compared to the patients who received lobectomy or hepatectomy and transplant. Approximately 70% of patients from our study population did not receive any HCC directed surgical intervention and among this, more than 40% of patients were with single nodule in the liver. Survival in patients with HCC has improved since 2008, which is limited to early stage HCC. Survival of advanced stage HCC patients is extremely poor and has not shown any significant improvement since the approval of sorafenib, emphasizing the need for better therapeutic options. Not receiving any surgical intervention is associated with significantly poor prognosis. Large numbers of early stage HCC patients were not able to receive surgical interventions. This can impose a significant financial burden, as these patients would progress on to the advanced stage, where treatment options are very limited and not as cost-effective. This emphasizes the need for further research to identify various barriers and the possible need for healthcare policy changes.

Survival of elderly patients with advanced hepatocellular carcinoma with distant metastasis in pre- and post- sorafenib era: A population based study.

e15643 Background: Sorafinib was approved for advanced hepatocellular carcinoma in 2007. This study was conducted to study relative survival in elderly patients with advanced hepatocellular carcinoma in presorafinib and sorafinib era. Methods: We selected elderly patients (age ≥ 65 years) with advanced hepatocellular carcinoma (distant metastasis based on SEER’s LRD staging) from the Surveillance, Epidemiology, and End Results (SEER) database diagnosed during January 2000 to December 2013. We calculated one year and five year relative survival rates in pre- (2000-2006) and post- sorafinib (2008-2013) era by sex and ethnicity (Caucasians, African-Americans (AA) &amp; Other) using SEER*Stat software. Results: There were total of 1533 patients in presorafinib era and 1694 patients in postsorafinib era. Of the total population, 71.30% were male and 28.70% female, 71% were Caucasian, 10% African-American and 19% were other race. Median age of patients was 73 years (65-99 years) and medial follow up period was 3 months (0-167 months) Survival rates improved significantly from pre- to post- sorafenib era (1 year RS: 10.60% ±0.80% vs 12.10±0.90%, p value = 0.001; 5 year RS: 1.10%±0.30% vs 1.8%±0.6%, p value = 0.001 ). The survival rate improved significantly for male (1 year RS: 11.60%±1.00% vs 12.30%±1.00%, p value = 0.006; 5 year RS: 1.00%±0.40% vs 1.3%± 0.6% , p value = 0.007) and Caucasian (1 year RS: 10.60%±1.00% vs 12.60%±1.10%, p value = 0.0008; 5 year RS: RS = 1.20%±0.40% vs 1.4%±0.7%, P value = 0.001) patients in post sorafenib era. There was no significant difference in the survival rates among any other cohorts examined.However in black (N = 153 vs 158 , RS = 6.80%±2.10% vs 7.80%±2.40% , p value = 0.77) or other races (N = 311 vs 311, RS = 12.20%±1.90% vs 12.80%±2.10%, p value = 0.30 ) , no significant improvement in survival was noted. Conclusions: Our study showed that relative survival rates of elderly patients with advanced hepatocellular carcinoma with distant metastasis has improved in the post-sorafenib compared to pre-sorafenib era. The improvement in survival is limited to male and Caucasian patients.

Hepatocellular carcinoma (HCC): beyond sorafenib-chemotherapy.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with poor prognosis. The incidence of HCC and HCC-related deaths have increased over the last several decades. However, the treatment options for advanced HCC are very limited. Sorafenib remains the only drug approved for systemic treatment for advanced HCC. However, prior to sorafenib era conventional cytotoxic chemotherapies have been studied in advanced HCC. In this review, clinical studies of systemic chemotherapy for advanced HCC will be summarized and discussed.

Survival difference among patients with hepatocelluar carcinoma (HCC) based on stage of disease: The pre- and post-sorafenib era.

411 Background: Sorafenib was approved for unresectable and metastatic HCC in 2007. We conducted this retrospective study using U.S. Surveillance, Epidemiology and End results (SEER) database to evaluate the relative survival rates of HCC patients before and after the approval of sorafenib. Methods: We analyzed SEER database: Incidence - SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2015 Sub (1973-2013 varying). Relative survival at 12,24,36,48 and 60 months interval was measured for patients diagnosed with HCC between 2001 and 2013. Relative survival rates were compared between pre sorafenib (2001-2007) and post sorafenib (2008-2013) eras. Results: A total of 54,901 patients (23,963 in pre sorafenib era and 30,938 in post-sorafenib era) were reported with HCC in SEER database. Relative survival at 5-years significantly improved for HCC patients diagnosed after 2007 (16.00±0.30% vs 18.90±0.30% for pre and post sorafenib era respectively; P-value &lt; 0.001). Relative survival for HCC patients with the solitary tumor was significantly improved (33.10±0.80% vs 35.40±0.90% survival at 5 years for pre and post sorafenib era respectively; P-value &lt; 0.001). Similarly, survival was found to be significantly improved for patients with multiple tumors without vascular invasion (17.10±0.70% vs 19.40±0.80% survival at 5 years for pre and post sorafenib era respectively; p-value &lt; 0.001). Relative survival continued to be poor with no statistically significant difference at any intervals for patients with tumor with vascular invasion (P-value 0.748) or distant metastasis (P-value 0.055). Survival difference was not significant among different age groups and gender between pre and post sorafenib eras. Conclusions: While relative survival significantly improved in post sorafenib era, it is largely limited to patients with the localized disease with the solitary tumor or multiple tumors without any vascular invasion or metastasis. Survival in patients with advanced stage HCC remains poor and has not shown significant improvement since the approval of sorafenib. The study shows better alternatives are needed for advanced-stage unresectable HCC patients.

Outcome and cause of death of hepatocellular carcinoma patients with extrahepatic metastases.

456 Background: Sorafenib is an orally active multi-kinase inhibitor that has been approved for the treatment of advanced hepatocellular carcinoma (HCC). Advanced HCC patients often exhibit two co-existing and life-threatening factors, cancer and cirrhosis, complicating prognostic evaluations. The present study investigated the survival and causes of death of HCC patients with extrahepatic metastases in the sorafenib era. Methods: We retrospectively analyzed 72 HCC patients with extrahepatic metastases who had received sorafenib. The causes of death among the HCC patients were classified as either hepatic causes (HC) or non-hepatic causes (NHC). Each cause of death was analyzed in the two subgroups. We then compared and assessed their clinical features and outcomes using the Chi square test, the Kaplan-Meier method, and a multivariate analysis. Results: Of the 72 HCC patients (female/male, 12/60), 50 patients had died at the time of the analysis. The median age was 66 (range, 30-84) years. At the time when sorafenib was started, the number of patients with a performance status of 0, 1, or 2 was 63 (88%), 8 (11%), and 1 (1%), respectively, and the number of patients with Child-Pugh class A, and B were 67 (93%), and 5 (7%), respectively. The median survival time and the 1-year survival rate were 11.8 (95% confidence interval 5.3-18.3) months and 49.7%, respectively. The incidence of HC and NHC was 29 (58%) and 21 (42%), respectively. Differences between the HC group and the NHC group were examined according to the patient characteristics, and the following significant differences were observed: main portal vein invasion (P&lt;.05), intrahepatic tumor stage (P&lt;.05), alpha-fetoprotein (AFP) (P&lt;.05), and the des-gamma-carboxy-prothrombin level (P&lt;.05). A multivariate analysis showed that portal vein invasion (hazard ratio [HR] = 2.29, P&lt;.05), a Child-Pugh B status (HR = 7.19, P&lt;.01), and high serum levels of AFP (HR = 2.18, P&lt;.05) were independent predictors of a poor outcome, respectively. Conclusions: This study revealed differences in the clinical characteristics at the time of the start of sorafenib between patients with HC and NHC death. The present results may be useful in the design and analysis of future clinical trials.

Hepatocellular cancer (HCC) patients on phase I clinical trials in sorafenib era: Analysis of a single institution experience in last 10 years.

e15134 Background: Sorafenib is the only approved systemic therapy in HCC. Clinical trials in HCC often exclude patients with Child-Pugh Stage (CPS) B/C cirrhosis. Furthermore, limited information on outcomes specific to HCC population are reported from early clinical trials. We evaluated the efficacy and safety of early phase clinical trial agents in HCC. Methods: We analyzed 53 Phase I clinical trials that enrolled HCC patients at our institution between 2003–2013. Median progression free survival (mPFS) and overall survival (mOS) were estimated from Kaplan-Meier curves along with medians and groups were compared with the log rank test. The magnitude of association and survival was estimated with the hazard ratio (HR). Results: Median age 63 (33–84), males 75 %, ECOG PS 0–1 92%, CPS A 19%, B 71.7% and C 9.4%. 41.5% subjects were treated with prior Sorafenib. Class of agents used included cytotoxics such as microtubule inhibitors (26.4%), anti-folates (5.7%), alkylators (1.9%), topoisomerase inhibitors (...

Clinical factors related to recurrence after hepatic arterial concurrent chemoradiotherapy for advanced but liver-confined hepatocellular carcinoma

Before the sorafenib era, advanced but liver-confined hepatocellular carcinoma (HCC) was treated by liver-directed therapy. Hepatic arterial concurrent chemoradiotherapy (CCRT) has been performed in our group, giving substantial local control but frequent failure. The aim of this study was to analyze patterns of failure and find out predictive clinical factors in HCC treated with a liver-directed therapy, CCRT. A retrospective analysis was done for 138 HCC patients treated with CCRT between May 2001 and November 2009. Protocol-based CCRT was performed with local radiotherapy (RT) and concurrent 5-fluorouracil (5-FU) hepatic arterial infusion chemotherapy (HAIC), followed by monthly HAIC (5-FU and cisplatin). Patterns of failure were categorized into three groups: infield, intrahepatic-outfield and extrahepatic failure. Treatment failure occurred in 34.0% of patients at 3 months after RT. Infield, intrahepatic-outfield and extrahepatic failure were observed in 12 (8.6%), 26 (18.7%) and 27 (19.6%) patients, respectively. Median progression-free survival for infield, outfield and extrahepatic failure was 22.4, 18 and 21.5 months, respectively. For infield failure, a history of pre-CCRT treatment was a significant factor (P = 0.020). Pre-CCRT levels of alpha-fetoprotein and prothrombin induced by vitamin K absence or antagonist-II were significant factors for extrahepatic failure (P = 0.029). Treatment failures after CCRT were frequent in HCC patients, and were more commonly intrahepatic-outfield and extrahepatic failures than infield failure. A history of pre-CCRT treatment and levels of pre-CCRT tumor markers were identified as risk factors that could predict treatment failure. More intensified treatment is required for patients presenting risk factors.

Survival trends among patients with advanced hepatocellular carcinoma in the United States.

329 Background: Sorafenib was approved by FDA for treatment of HCC in 2007. This study was conducted to evaluate survival outcome in advanced HCC during 2005-2006 and 2008-2009 using U.S. Surveillance, Epidemiology, and End Results (SEER) cancer registry database.Methods: We analyzed the Surveillance, Epidemiology, and End Results (SEER*Stat) database: Incidence - SEER 18 Regs Research Data + Hurricane Katrina Impacted Louisiana Cases, Nov 2011 Sub (1973-2009 varying) using MP-SIR session. We analysed 1 year relative survival rates among stage IV HCC patients between pre- sorafenib (2005- 2006) and post- sorafenib (2008- 2009) eras. We used seer Z test to compare relative survival rates among cohorts of patients categorized by gender and age groups (&lt;50 and &gt;50 years). Results: There were 2,497 (1,180 in pre-sorafenib era and 1,317 in post-sorafenib era) stage IV HCC patients reported in seer database. Overall 1 year relative survival rates ± standard error (SE) were: 12.5±0.7% (12.5±1% in pre sorafenib era vs 13.1±1.1% in post sorafenib era, Z score= 0.481, p value=0.63). Overall Relative survival rates among men and women were 12.9±0.8% (12.7±1.1% in pre vs 13.4±1.2 in post sorafenib era, Z score=0.254, p value=0.79) and 11.8±1.6% (11.7±2.2% in pre vs 11.5±2.5 post sorafenib era, Z score=0.469, p value=0.63) respectively. There was no significant differences between 1 year relative survival rates by age groups (&lt;50 and &gt;50 years). Conclusions: This study showed no significant difference in 1-year relative survival rates during 2008-2009 as compared to 2005-2006. More studies are required to find out why the findings of SHARP trial have not translated to population-based settings.[Table: see text]

Screening for extrahepatic metastases by additional staging modalities is required for hepatocellular carcinoma patients beyond modified UICC stage T1.

Accurate staging of hepatocellular carcinoma (HCC) is critical for guiding optimal treatment, and the presence of extrahepatic metastases (EHM) can seriously affect the optimal choice of treatment in the sorafenib era. However, there is limited data about when and how to screen EHM for newly diagnosed HCC patients, especially for patients without symptoms or signs of EHM. We analyzed 314 newly diagnosed HCC patients who had no symptoms or signs of EHM and who had undergone additional modalities. EHM was found in 50 of 314 patients (15.9%). Fifteen of 50 EHM (30%) were missed by conventional modalities but revealed by additional modalities. The frequency of EHM were 0% (0/26), 7.6% (10/131), 25.0% (30/120) and 27.0% (10/37) for the modified UICC stages T1, T2, T3 and T4, respectively (p<0.001). The proportions of EHM detected by additional modalities were 50% (5/10 EHM), 33% (10/30 EHM) and 0% (0/10 EHM) for modified UICC stages T2, T3 and T4, respectively. Application of additional staging modalities resulted in change of HCC stage in a significant proportion of HCC patients beyond modified UICC stage T1 by revealing EHM that had not been detected by conventional modalities.

Novel antiangiogenic therapies against advanced hepatocellular carcinoma (HCC)

Angiogenesis is a cornerstone in the process of hepatocarcinogenesis. In the sorafenib era, other antiangiogenic targeted drugs, such as monoclonal antibodies and a new generation of tyrosine kinase inhibitors, have been shown in phase II trials to be safe and effective in the treatment of advanced hepatocellular carcinoma. Several currently active phase III trials are testing these drugs, both in first- and second-line settings. Strategies to overcome primary and acquired resistance to antiangiogenic therapy are urgently needed. Novel biomarkers may help in improving the efficacy of drugs targeting angiogenesis.

Recurrent hepatocellular carcinoma in liver transplant recipients: Parameters affecting time to recurrence, treatment options and survival in the sorafenib era

A growing number of patients with hepatocellular carcinoma undergo liver transplantation, but there is little data on recurrence and its treatment in the posttransplant setting. This article presents a retrospective analysis of adult hepatocellular carcinoma patients. The aim of the study was to characterize the clinical pattern of posttransplant hepatocellular carcinoma recurrence, treatment options in recurrence and overall survival after liver transplantation and after recurrence. A total of 139 patients with histological proven hepatocellular carcinoma was included in the study. The median follow-up after liver transplantation was 37.2 months. Twenty-four of 139 patients experienced a recurrence. In 72.7% of the cases, the hepatocellular carcinoma recurred outside the transplant. Median overall survival after recurrence was 23.1 months. A total of 68.2% of patients received a mean of 2.2 treatments for posttransplant hepatocellular carcinoma recurrence. While on treatment with sorafenib, the use of mTOR inhibitors and radiotherapy had no statistically significant effect on overall survival, complete surgical resection of metastatic lesions significantly improved overall survival. Non-resectable patients with isolated hepatic relapse also benefited from local control strategies. Posttransplant hepatocellular carcinoma recurrence frequently is located outside the transplant, and despite the proven efficacy of sorafenib, complete surgical resection of metastatic lesions remains the hallmark of treatment.

Sorafenib versus cytotoxic chemotherapy for patients with advanced hepatocellular carcinoma: A retrospective, single-institution study.

339 Background: Prior to the sorafenib era, most of the advanced hepatocellular carcinoma (HCC) patients had to rely only on conventional cytotoxic chemotherapy. But the introduction of sorafenib in 2008 had given HCC patients additional option for their treatment. However, given that sorafenib has been a nonreimbursable drug under the Korea public health system, most of treatment strategy has largely been determined by patients' affordability of the drug rather than by difference in efficacy and toxicity of the two treatments. Therefore, we compared the efficacy and toxicity of the two treatments by observing HCC patients. Methods: From January 2002 to December 2009, 173 patients with unresectable HCC had been retrospectively analyzed. Among them, 44 (25.4%) had been treated with sorafenib and the remaining had received cytotoxic chemotherapy. We evaluated objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and toxicity profiles. Results: The median OS of sorafenib group was 23.0 weeks (95% CI, 8.1-37.9) vs. 43.6 weeks (95% CI, 34.0-37.9) for cytotoxic chemotherapy group. The median PFS for sorafenib group was 11.1 weeks (95% CI, 6.5-15.8) versus 12.4 weeks (95% CI, 8.1-16.7) for cytotoxic chemotherapy group. However, the difference in both findings had not been statistically significant (p=0.105 and p=0.496, respectively). ORR and DCR for sorafenib group were 2.3% and 52.3% versus 6.2% and 43.4% for cytotoxic chemotherapy group, respectively. Patients treated with chemotherapy had shown higher frequencies of grade 3 or 4 neutropenia, 19.7%, (vs. 0% for sorafenib). However, the group with sorafenib had reported a higher rate of all grade dermatologic toxicities such as hand-foot skin reaction, rash and pruritus. Conclusions: Our analysis indicates that efficacy of conventional chemotherapy is not inferior to that of sorafenib. Further research including novel target agent and cytotoxic chemotherapy is needed to improve clinical outcomes for advanced HCC. No significant financial relationships to disclose.