Current Role of Atezolizumab Plus Bevacizumab Therapy in the Sequential Treatment of Unresectable Hepatocellular Carcinoma

Abstract Background Atezolizumab plus bevacizumab therapy is the new standard treatment option for advanced hepatocellular carcinoma (HCC). The clinical details and sequential course after atezolizumab plus bevacizumab therapy remain to be determined. Methods From October 2020 to June 2021, 34 consecutive patients who received atezolizumab plus bevacizumab therapy were evaluated. Their clinical outcomes were assessed according to liver function classified by modified albumin-bilirubin (ALBI) grade 1 and 2a (1/2a) versus 2b and treatment line (first-line versus second- or later-line). Furthermore, the treatment sequence after atezolizumab plus bevacizumab therapy was also assessed. Results The objective response and disease control rates were 15.6% and 93.8%, respectively. The median proportions of ALBI scores at 1, 2, and 3 months relative to the baseline scores were 0.94, 0.97, and 0.93, respectively. The median proportions of α-fetoprotein (AFP) scores at 1, 2, and 3 months relative to the baseline scores were 0.98, 1.12, and 1.83, respectively. There were no significant differences in the changes in the proportions of AFP and ALBI scores according to both liver function and treatment line. Twelve patients were administered lenvatinib treatment after the failure of atezolizumab plus bevacizumab therapy. The proportions of AFP and ALBI scores at 1 month relative to the baseline scores were 0.55 and 0.81, respectively. Conclusions Atezolizumab plus bevacizumab therapy can be administered effectively for advanced HCC irrespective of patients’ liver function and treatment line. Lenvatinib administration after atezolizumab plus bevacizumab therapy can be effective, although special attention should be paid to the deterioration of liver function.

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Potential of Lenvatinib for an Expanded Indication from the REFLECT Trial in Patients with Advanced Hepatocellular Carcinoma

Liver Cancer ◽

10.1159/000507022 ◽

2020 ◽

Vol 9 (4) ◽

pp. 382-396 ◽

Cited By ~ 3

Author(s):

Susumu Maruta ◽

Sadahisa Ogasawara ◽

Yoshihiko Ooka ◽

Masamichi Obu ◽

Masanori Inoue ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Function ◽

Objective Response ◽

Dose Intensity ◽

Advanced Hepatocellular Carcinoma ◽

First Line ◽

High Burden ◽

Advanced Hcc ◽

Class B ◽

Pugh Class

Background: The present study aimed to assess the efficacy and safety of lenvatinib and verify the possibility of lenvatinib for the expanded indication from the REFLECT trial in patients with advanced hepatocellular carcinoma (HCC) in real-world practice, primarily focusing on the population that was excluded in the REFLECT trial. Methods: We retrospectively collected data on patients with advanced HCC who were administered lenvatinib in 7 institutions in Japan. Results: Of 152 advanced HCC patients, 95 and 57 patients received lenvatinib in first-line and second- or later-line systemic therapies, respectively. The median progression-free survival in Child-Pugh class A patients was nearly equal between first- and second- or later-line therapies (5.2 months; 95% CI 3.7–6.9 for first line, 4.8 months; 95% CI 3.8–5.9 for second or later line, p = 0.933). According to the modified Response Evaluation Criteria in Solid Tumors, the objective response rate of 27 patients (18%) who showed a high burden of intrahepatic lesions (i.e., main portal vein and/or bile duct invasion or 50% or higher liver occupation) at baseline radiological assessment was 41% and similar with that of other population. The present study included 20 patients (13%) with Child-Pugh class B. These patients observed high frequency rates of liver function-related adverse events due to lenvatinib. The 8-week dose intensity of lenvatinib had a strong correlation with liver function according to both the Child-Pugh and albumin – bilirubin scores. Conclusion: Lenvatinib had potential benefits for patients with advanced HCC with second- or later-line therapies and a high burden of intrahepatic lesions. Dose modification should be paid increased attention among patients with poor liver function, such as Child-Pugh class B patients.

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Non-immunotherapy options for the first-line management of hepatocellular carcinoma: exploring the evolving role of sorafenib and lenvatinib in advanced disease

Current Oncology ◽

10.3747/co.27.7159 ◽

2020 ◽

Vol 27 (S3) ◽

Author(s):

S. Perera ◽

D. Kelly ◽

G. M. O'Kane

Keyword(s):

Hepatocellular Carcinoma ◽

Kinase Inhibitor ◽

Treatment Options ◽

Optimal Timing ◽

Advanced Hepatocellular Carcinoma ◽

Line Treatment ◽

First Line ◽

First Line Treatment ◽

Line Management

The results of the sharp trial established sorafenib, a tyrosine kinase inhibitor (TKI), as the sole first-line treatment option in advanced hepatocellular carcinoma (HCC) for more than a decade. In 2020, there has been a surge in new therapies for hcc, including immunotherapeutic strategies and the approval of a number of novel tkis. In addition to sorafenib, lenvatinib and combination atezolizumab–bevacizumab now represent standard first-line treatment options. As those systemic options begin to be better utilized, assurance of adequate liver function and optimal timing are required to improve patient outcomes. Furthermore, sequencing of the agents will have to be carefully tailored, given the increasing armamentarium of choices. Here, we discuss the role of lenvatinib and sorafenib in the first-line management of HCC.

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Comparison of systemic therapy efficacy in advanced hepatocellular carcinoma: Systematic review and frequentist network meta-analysis of randomized controlled trials.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.293 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 293-293

Author(s):

Robin Park ◽

Laércio Lopes da Silva ◽

Voravech Nissaisorakarn ◽

Ivy Riano ◽

Anwaar Saeed

Keyword(s):

Hepatocellular Carcinoma ◽

Systematic Review ◽

Meta Analysis ◽

Objective Response ◽

Indirect Comparison ◽

Advanced Hepatocellular Carcinoma ◽

Second Line ◽

First Line ◽

Line Setting ◽

Systemic Agents

293 Background: Several systemic agents are approved for use in the first line and second line treatment settings for advanced hepatocellular carcinoma (aHCC). However, choosing among available options in both first and second line settings remain difficult due to the paucity of head-to-head comparative trials. Therefore, we have conducted a systematic review and network meta-analysis for the indirect comparison of the systemic agents in the first line and second line settings. Methods: Published clinical trials that have evaluated systemic agents in the first line and second line settings in advanced HCC from inception to April 2020 were identified by searching PubMed, EMBASE, and Cochrane Databases and abstracts presented in the main annual ASCO and ESMO conferences from 2017 to 2020. Studies published in English providing clinical outcomes data including overall survival (OS), progression free survival (PFS) and objective response rate (ORR) were included in the analysis. The primary outcomes of interest were pooled hazard ratios (HR) of OS and OR of ORR in first line studies and HR of PFS and OR of ORR for second line studies. OS for second line agents were synthesized in a qualitative analysis. Results: Overall, 8,335 patients (13 studies) and 4,612 patients (11 studies) were analyzed in phase II/III trials for first line and second line settings respectively. In the first line setting, atezolizumab plus bevacizumab and lenvatinib were ranked highest as the regimens associated with the greatest OS (A+B, HR 0.58, 95% CI, 0.42-0.80; P-score 0.993) and ORR (lenva, OR 3.34, 95% CI, 2.17-5.14; P-score 0.080) respectively. In the second line setting, cabozantinib showed the highest probability of greatest PFS benefit (HR 0.44, 95% CI, 0.29-0.66; P-score 0.854) as well as the highest probability of greatest ORR benefit (cabo, OR 9.40, 95% CI, 1.25-70.83, P-score, 0.266). Conclusions: In the first line setting, atezolizumab plus bevacizumab may be the superior regimen whereas lenvatinib may be considered as the initial option when robust tumor responses are preferred. In the second line setting, cabozantinib may be the preferred option including in cases when robust tumor responses are favored.

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An exploratory study of sorafenib plus toripalimab for unresectable hepatocellular carcinoma with portal vein tumor thrombus.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.tps4658 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. TPS4658-TPS4658

Author(s):

Yu Yang ◽

Qiu Li

Keyword(s):

Hepatocellular Carcinoma ◽

Monoclonal Antibody ◽

Portal Vein ◽

Checkpoint Inhibitors ◽

Objective Response ◽

Progression Free Survival ◽

Advanced Hepatocellular Carcinoma ◽

Line Treatment ◽

First Line ◽

First Line Treatment

TPS4658 Background: Portal vein tumor thrombosis (PVTT) is common among advanced hepatocellular carcinoma ( HCC), resulting in poor prognosis. As the standard first-line treatment, the efficacy of Sorafenib is not satisfactory in HCC with PVTT. Although immune checkpoint inhibitors have made a breakthrough in treatment of advanced HCC, objective response rate (ORR) of anti-PD-1 monoclonal antibody monotherapy is only 17-20%. Recently, PD-1/PD-L1 inhibitors combined with anti-angiogenesis therapy have shown good efficacy in the clinical studies. However, the data on immunotherapy for HCC with PVTT are still limited. Toripalimab is the first Chinese-produced anti-PD-1 monoclonal antibody marketed. We designed the study to evaluate the efficacy and safety of Sorafenib plus Toripalimab as the first-line treatment for unresectable HCC with PVTT. Methods: The study is a multicenter, single-arm, phase Ib/II trial. The primary objectives are 6-month progression-free survival (PFS) rate and safety. Secondary objectives include ORR, disease control rate, PFS, overall survival. The escalation stage includes two dose cohorts: Sorafenib 400 mg po qd or 400 mg bid combined with Toripalimab 240 mg iv d1 q3w. 6-12 patients are estimated to evaluate the dose-limiting toxicity within the first 42 days of administration. In the expansion stage, patients are treated with the recommended dose based on the escalation stage, until progressive disease or intolerable toxicity. Assuming Sorafenib plus Toripalimab can improve the 6-month PFS rate to 40% (Sorafenib:20%, β = 0.2, α = 0.05) and dropout is 10%, this stage need 39 patients. A total of 45-51 patients are enrolled. Major eligibility requirements include: unresectable HCC with diagnoses confirmed histologically or cytologically, or confirmed clinically in accordance with Chinese guideline for HCC diagnosis and treatment (v2017); radiographic evidence of PVTT; age ≥18 and < 75 years; at least one measurable lesion according to RECIST 1.1; a predicted life expectancy ≥ 3 months; ECOG PS≤1, Child-Pugh class A or B (≤7); no any prior systemic anti-cancer treatment; adequate organ function. Patients with hepatitis B treated with antiviral therapy (viral load < 100 IU/mL) or patients with chronic hepatitis C can be included. The study is open and actively enrolling at time of submission. Clinical trial information: NCT04069949 .

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Donafenib versus sorafenib as first-line therapy in advanced hepatocellular carcinoma: An open-label, randomized, multicenter phase II/III trial.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4506 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4506-4506 ◽

Cited By ~ 4

Author(s):

Feng Bi ◽

Shukui Qin ◽

Shanzhi Gu ◽

Yuxian Bai ◽

Zhendong Chen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Phase Ii ◽

Objective Response ◽

Advanced Hepatocellular Carcinoma ◽

First Line ◽

Open Label ◽

Multikinase Inhibitor ◽

First Line Therapy ◽

Line Therapy ◽

Number Of Patients

4506 Background: Sorafenib is still the standard first-line therapy for advanced hepatocellular carcinoma (HCC). Donafenib, a novel multikinase inhibitor, showed potential benefits in a previous phase Ib study in HCC. Methods: In this open-label, randomized phase II/III trial (ZGDH3), patients with unresectable or metastatic HCC, a Child-Pugh liver function score ≤ 7, and no prior systemic therapy were enrolled from 37 sites across China and randomized (1:1) to receive oral donafenib (0.2 g) or sorafenib (0.4 g) twice daily until intolerable toxicity or disease progression. The primary endpoint was overall survival (OS). Efficacy analysis was primarily based on the full analysis set (FAS). Results: Between March 2016 and April 2018, 668 patients were randomized (donafenib, 334; sorafenib, 334) and included in the intention-to-treat (ITT) set, of whom 659 were analysed by FAS (328 vs 331). Donafenib was associated with a significantly longer median OS than sorafenib in both FAS (12.1 months vs 10.3 months, hazard ratio 0.831, 95% confidence interval 0.699–0.988, p = 0.0363) and ITT (12.0 months vs 10.1 months, 0.839, 0.706–0.996, p = 0.0446). There were no significant differences in median progression-free survival (3.7 months vs 3.6 months, p = 0.2824), objective response rate (4.6% vs 2.7%, p = 0.2448), and disease control rate (30.8% vs 28.7%, p = 0.5532). Grade 3 or worse adverse events (AEs) occurred in 191 (57.4%) and 224 (67.5%) patients ( p = 0.0082), respectively, and AEs of special interest and those leading to treatment interruption occurred in 287 (86.2%) vs 309 (93.1%, p = 0.0049) and 101 (30.3%) vs 141 (42.5%, p = 0.0013). A numerically lower number of patients reported serious AEs (55 [16.5%] vs 67 [20.2%], p = 0.2307) with donafenib. Common AEs with donafenib included hand-foot skin reaction (50.5%), aspartate aminotransferase increased (40.5%), blood bilirubin increased (39.0%), platelet count decreased (37.8%), and diarrhea (36.6%). Conclusions: Donafenib significantly improves OS over sorafenib with favourable safety and tolerability. Donafenib is a promising superior first-line therapy for advanced HCC. Funding: Zelgen. Clinical trial information: NCT02645981 .

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Real-world efficacy and safety of lenvatinib-base therapy for patients with unresectable hepatocellular carcinoma in China: A multicenter retrospective analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16192 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16192-e16192

Author(s):

Qicong Mai ◽

Song Chen ◽

Feng Shi ◽

Zhiqiang Mo ◽

Jian He ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Real World ◽

Objective Response ◽

Progression Free Survival ◽

Tumor Burden ◽

Phase Iii ◽

Advanced Hepatocellular Carcinoma ◽

First Line ◽

Grade 3

e16192 Background: Lenvatinib has been approved as a first-line systemic for advanced hepatocellular carcinoma (HCC) after the randomized phase III REFLECT trial. The aim of this study was to assess the lenvatinib-base treatment patterns and safety in real-world clinical settings in China. Methods: In this multicenter retrospective study, A total of 278 patients with unresectable HCC were treated with lenvatinib-base treatment between October 2018 and November 2020 were analyzed. Therapeutic effect was determined using the RECIST 1.1 and mRECIST criteria. Progression free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAE) were also evaluated. Results: Of 278 unresectable HCC patients (median age: 56.1±11.9 years), 220 (79.1%) had cirrhosis caused by HBV infection. 215 (77.3%) and 63 (22.7%) patients were classified as Child-pugh A and B class, respectively. 233 (83.8%) and 45 (16.2%) patients received lenvatinib in first-line and second-line systemic therapies, respectively. 223 (80.2%) patients were treated with lenvatinib plus arterially directed therapy (TACE or HAIC of FOLFOX) and 55 (19.8%) were treated with lenvatinib alone. The objective response rate were 34.9% (RECIST) and 47.5% (mRECIST), while the disease control rate were 75.5%. With a median follow-up period of 12.8 months, the median PFS and OS were 7.8 months (95% CI 7.1–8.4) and 17.2 months (95% CI 14.9–19.6), respectively. Results from the multivariate analysis showed that the significant independent favorable prognosis factors were tumor burden< 50% (P=0.033), Child–Pugh A class (P<0.01), AFP level <200ng/mL (P=0.045), the combination with lenvatinib and arterially directed therapy (P<0.01). TRAE occurred in 219 of 278 patients (78.8%), most common TRAE were hypertension (n=118; 42.4%) and hand-foot skin reaction (n=91; 32.7%). The most common grade 3–4 TARE were hypertension (n=23; 8.3%), decreased appetite (n=18; 6.5%), AST elevation (n=14; 5%), and diarrhea (n=14; 5%) across all study patients. Conclusions: In this multicenter real-world study, lenvatinib-base treatment could be accomplished with well tolerated and response for unresectable HCC patients. Combination with arterially directed therapy could likely improve the overall survival.

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The Prognostic Value of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Patients with Hepatocellular Carcinoma Receiving Atezolizumab Plus Bevacizumab

Cancers ◽

10.3390/cancers14020343 ◽

2022 ◽

Vol 14 (2) ◽

pp. 343

Author(s):

Jing-Houng Wang ◽

Yen-Yang Chen ◽

Kwong-Ming Kee ◽

Chih-Chi Wang ◽

Ming-Chao Tsai ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Objective Response ◽

Progression Free Survival ◽

Neutrophil To Lymphocyte Ratio ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Lymphocyte Ratio ◽

Third Line

Atezolizumab plus bevacizumab has been approved as the first-line systemic treatment for patients with unresectable hepatocellular carcinoma (uHCC). This study was designed to assess the clinical impact of atezolizumab plus bevacizumab in uHCC patients. A total of 48 uHCC patients receiving atezolizumab plus bevacizumab were identified, including first-line, second-line, third-line, and later-line settings. In these patients, the median progression-free survival (PFS) was 5.0 months, including 5.0 months for the first-line treatment, not reached for the second-line treatment, and 2.5 months for the third line and later line treatment. The objective response rate and disease control rate to atezolizumab plus bevacizumab were 27.1% and 68.8%, respectively. The severity of most adverse events was predominantly grade 1–2, and most patients tolerated the toxicities. The ratios of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte (PLR) were used to predict PFS in these patients. The optimal cutoff values of NLR and PLR were 3 and 230, and NLR and PLR were independent prognostic factors for superior PFS in the univariate and multivariate analyses. Our study confirms the efficacy and safety of atezolizumab plus bevacizumab in uHCC patients in clinical practice and demonstrates the prognostic role of NLR and PLR for PFS in these patients.

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Posttreatment after Lenvatinib in Patients with Advanced Hepatocellular Carcinoma

Liver Cancer ◽

10.1159/000515552 ◽

2021 ◽

pp. 1-12

Author(s):

Keisuke Koroki ◽

Naoya Kanogawa ◽

Susumu Maruta ◽

Sadahisa Ogasawara ◽

Yotaro Iino ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cox Regression ◽

Objective Response ◽

Lower Probability ◽

Advanced Hepatocellular Carcinoma ◽

Second Line ◽

First Line ◽

Sorafenib Treatment ◽

The Third ◽

Third Line

Background: There is no standard posttreatment for patients with advanced hepatocellular carcinoma (HCC) in whom lenvatinib therapy has failed. This study aimed to investigate rates of migration to posttreatment after lenvatinib and to explore candidates for second-line agents in the patients with failed lenvatinib therapy. Methods: We retrospectively collected data on patients with advanced HCC who received lenvatinib as the first-line agent in 7 institutions. Results: Overall survival and progression-free survival (PFS) of 178 patients who received lenvatinib as the first-line agent were 13.3 months (95% confidence interval [CI], 11.5–15.2) and 6.7 months (95% CI, 5.6–7.8), respectively. Sixty-nine of 151 patients (45.7%) who discontinued lenvatinib moved on to posttreatment. The migration rates from lenvatinib to the second-line agent and from the second-line agent to the third-line agent were 41.7 and 44.4%, respectively. Based on multivariate analysis, response to lenvatinib (complete or partial response according to modified RECIST) and discontinuation of lenvatinib due to radiological progression, as well as male were associated with a significantly higher probability of migration to posttreatment after lenvatinib. On the other hand, alpha-fetoprotein levels of 400 ng/mL or higher was correlated with a significantly lower probability of migration to posttreatment after lenvatinib. Of 63 patients who received second-line systemic therapy, 53 (84.2%) were administered sorafenib. PFS, objective response rate (ORR), and disease control rate (DCR) for sorafenib treatment were 1.8 months (95% CI, 0.6–3.0), 1.8%, and 20.8%, respectively. According to the Cox regression hazard model, Child-Pugh class B significantly contributed to shorter PFS. PFS, ORR, and DCR of 22 patients who received regorafenib after lenvatinib in any lines were 3.2 months (range, 1.5–4.9 months), 13.6%, and 36.3%, respectively. Similarly, PFS, ORR, and DCR of 17 patients who received regorafenib after lenvatinib in the third-line (after sorafenib) were 3.8 months (range, 1.1–6.5 months), 17.6%, and 41.2%, respectively. Conclusion: Sorafenib may not be a candidate for use as a posttreatment agent after lenvatinib, according to the results of the present study. Regorafenib has the potential to become an appropriate posttreatment agent after lenvatinib.

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Ipilimumab and nivolumab/pembrolizumab in advanced hepatocellular carcinoma refractory to prior immune checkpoint inhibitors

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-001945 ◽

2021 ◽

Vol 9 (2) ◽

pp. e001945 ◽

Cited By ~ 1

Author(s):

Jeffrey Sum Lung Wong ◽

Gerry Gin Wai Kwok ◽

Vikki Tang ◽

Bryan Cho Wing Li ◽

Roland Leung ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Objective Response ◽

Acquired Resistance ◽

Survival Rates ◽

Advanced Hepatocellular Carcinoma ◽

Primary Resistance ◽

Advanced Hcc

BackgroundProgrammed cell death protein 1 (PD-1) pathway blockade with immune checkpoint inhibitors (ICIs) is a standard therapy in advanced hepatocellular carcinoma (HCC) nowadays. No strategies to overcome ICI resistance have been described. We aimed to evaluate the use of ipilimumab and anti-PD-1 ICIs (nivolumab or pembrolizumab) combinations in patients with advanced HCC with progression on prior ICIs.MethodsPatients with advanced HCC with documented tumor progression on prior ICIs and subsequently received ipilimumab with nivolumab/pembrolizumab were analyzed. Objective response rate (ORR), median duration of response (DOR), time-to-progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were assessed.ResultsTwenty-five patients were included. The median age was 62 (range: 51–83). About 68% were of Child-Pugh (CP) Grade A and 48% had primary resistance to prior ICI. At median follow-up of 37.7 months, the ORR was 16% with a median DOR of 11.5 months (range: 2.76–30.3). Three patients achieved complete response. The median TTP was 2.96 months (95% CI: 1.61 to 4.31). Median OS was 10.9 months (95% CI: 3.99 to 17.8) and the 1 year, 2 year and 3 year survival rates were 42.4%, 32.3% and 21.6%, respectively. The ORR was 16.7% in primary resistance group and 15.4% in acquired resistance group (p=1.00). All responders were of CP A and Albumin-Bilirubin (ALBI) Grade 1 or 2. CP and ALBI Grades were significantly associated with OS (p=0.006 and p<0.001, respectively). Overall, 52% of patients experienced TRAEs and 12% experienced Grade 3 or above TRAEs.ConclusionsIpilimumab and nivolumab/pembrolizumab can achieve durable antitumor activity and encouraging survival outcomes with acceptable toxicity in patients with advanced HCC who had prior treatment with ICIs.

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Sorafenib-Regorafenib Sequential Therapy in Advanced Hepatocellular Carcinoma: A Single-Institute Experience

Digestive Diseases ◽

10.1159/000480257 ◽

2017 ◽

Vol 35 (6) ◽

pp. 611-617 ◽

Cited By ~ 9

Author(s):

Kazuomi Ueshima ◽

Naoshi Nishida ◽

Masatoshi Kudo

Keyword(s):

Hepatocellular Carcinoma ◽

Objective Response ◽

Progression Free Survival ◽

Sequential Therapy ◽

Advanced Hepatocellular Carcinoma ◽

Open Label ◽

Effective Treatment Option ◽

Sorafenib Treatment ◽

Advanced Hcc ◽

Grade 3

Objectives: Previously, no therapeutic agent has been known to improve the overall survival compared with placebo in patients with hepatocellular carcinoma (HCC), who have progressed after sorafenib. In this patient population, regorafenib was first demonstrated to confer a survival benefit in the RESORCE trial, and subsequently it was approved as a second-line treatment for patients with advanced HCC. An open-label expanded access program (EAP) of regorafenib was implemented for compassionate use. We investigated the efficacy and safety of regorafenib based on our experience of the RESORCE trial and the EAP. Methods: Data from 5 patients from the RESORCE trial and 6 from the EAP were analyzed retrospectively. All patients had tolerated prior sorafenib and were progressing during sorafenib treatment. Results: The median progression-free survival was 9.2 months (95% CI 2.3-16.1). One patient achieved a partial response and 7 achieved stable disease. The objective response rate was 9.1%, and the disease control rate was 72.7%. No treatment-associated mortalities were observed. Grade 3 hypophosphatemia was observed in 2 patients, grade 2 anorexia was observed in 5 patients, and grade 3 neutropenia was observed in 2 patients. Grade 2 and grade 3 thrombocytopenia were observed in 2 and 3 patients, respectively. All treatment-related adverse events were improved by reduction or interruption of regorafenib. Five patients showed decreased serum albumin levels. Conclusion: Sorafenib and regorafenib sequential therapy presents a safe and effective treatment option for patients with advanced HCC.

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