Transition of molecular target agent therapy in advanced hepatocellular carcinoma: A multicenter, retrospective study.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 317-317
Author(s):  
Kazufumi Kobayashi ◽  
Sadahisa Ogasawara ◽  
Aya Takahashi ◽  
Yuya Seko ◽  
Satoshi Tsuchiya ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Retrospective Study ◽  
Performance Status ◽  
Progression Free Survival ◽  
Staging System ◽  
Sequential Therapy ◽  
Molecular Target ◽  
Advanced Hepatocellular Carcinoma ◽  
Entire Cohort ◽  
Significant Difference

317 Background: There have been considerable advances in systemic chemotherapy for hepatocellular carcinoma (HCC) in recent times. Currently, four molecular target agents (MTA) are available for HCC treatment in Japan. Sequential therapy using multiple MTAs is being considered as the gold standard of treatment. However, the effectiveness of the treatment strategy transition for HCC remains unclear. The present study aimed to clarify the current practical use of MTAs and its effectiveness in HCC treatment. Methods: In this multicenter, retrospective study, we collected and analyzed the clinical data of 877 patients who underwent MTA therapy for HCC from June 2009 to March 2019 at several institutes in Japan. The patients were classified into 3 groups as per the period of initial MTA treatment beginning (period 1: 2009–2012, n = 267; period 2: 2013–2016, n = 352; period 3: 2017–2019, n = 258). These 3 periods were defined to have approximately same term. Period 3 means the era of multiple MTAs because of the approval of regorafenib in Japan in 2017. We assessed the patient characteristics, MTA use, and prognosis of the 3 groups. Results: The proportion of patients with advanced-stage HCC, defined according to the Barcelona Clinic Liver Cancer staging system, in each period was 70.1%, 66.5%, and 62.0% in period 1, 2, and 3, respectively. MTA use for intermediate stages increased with the passage of time ( p = 0.052). The proportion of multiple MTAs use was remarkably increased in the 3 groups (1.1%, 10.2%, and 42.6%, respectively, p < 0.0001). Child-Pugh score, proportion of macrovascular invasion, extrahepatic metastasis, and α-fetoprotein (AFP) ≥400 ng/mL showed no significant difference among the 3 groups. The median overall survival was 11.9 months for the entire cohort and 10.4, 11.3, and 15.2 months, for period 1, 2, and 3, respectively. It is noteworthy that the prognosis of patients with HCC improved over time ( p = 0.016). With respect to progression-free survival, the median value was 3.0 months for the entire cohort and 2.7, 2.8, and 4.7 months for period 1, 2, and 3, respectively ( p < 0.0001). The treatment duration was also prolonged with time (2.7, 3.2, and 6.6 months for period 1, 2, and 3, respectively; p < 0.0001). Multivariate analysis using Cox proportional hazard model showed that HCV infection, Child-Pugh score, performance status, α-fetoprotein ≥400 ng/mL, presence of macrovascular invasion, and period 3 for initial MTA introduction were independent prognostic factors. Conclusions: Sequential therapy with multiple MTAs has gained popularity with time and is considered to improve patient prognosis. The development of MTA therapy for HCC is expected to continue. Therefore, further studies are needed to help determine the appropriate drugs, the sequence of MTA use, and the precise transition time.

A retrospective study on the efficacy and safety of sorafenib or lenvatinib combined with sintilimab in patients with advanced hepatocellular carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16127-e16127
Author(s):  
Zhen Zeng ◽  
Linzhi Zhang ◽  
Tong Wu ◽  
Jiamin Cheng ◽  
Yan Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Retrospective Study ◽  
Adverse Events ◽  
Controlled Trial ◽  
Performance Status ◽  
Objective Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
Significant Difference ◽  
Grade 3

e16127 Background: To evaluate the efficacy and safety of sorafenib or lenvatinib combined with sintilimab in patients with advanced hepatocellular carcinoma. Methods: This retrospective study included patients with advanced/metastatic hepatocellular carcinoma who received sintilimab (iv. 200 mg, Q3W) combined with sorafenib (oral, 400 mg twice-daily) (cohort A) or lenvatinib (oral, 12 mg/day for bodyweight≥60 kg or 8 mg/day for bodyweight < 60 kg) (cohort B) as first line therapy between March 2019 to December 2020 in the 5th medical center of the PLA general hospital of China. The primary endpoint was Progression-Free Survival (PFS), and the secondary endpoints included the Objective Response Rate (ORR), Disease Control Rate (DCR), Overall Survival (OS), Time to Progression (TTP) and safety. Results: 45 patients were enrolled, of which 29 were in the cohort A and 16 were in the cohort B. Except for the extrahepatic metastasis (62.1% vs 25.0%, P= 0.029), there were no significant differences in age, gender, weight, ECOG performance status, Child-Pugh, BCLC staging, and the proportion of previous treatment regimens between the two cohorts. The mean (±SD) exposure cycles in the two cohorts were 7.2±6.7 vs 7.1±4.7 ( P= 0.584). The median PFS of cohort A (8.2 months, 95%CI 3.1-19.5) was longer than that of cohort B (5.2 months, 95%CI 2.0-10.8), but there was no significant difference (HR 0.55, 95%CI 0.24-1.29, P = 0.161). However, there was no significant difference between the two cohorts in ORR (24.1% vs 6.3%, P= 0.226), DCR (82.8% vs 75.0%, P= 0.700) and median TTF (8.2 vs 4.6months, HR 0.49, 95%CI 0.21- 1.10, P= 0.074). OS data were not yet mature. There was no significant difference in the incidence of all grades and grade 3-4 adverse events between the two cohorts. The most common grade 3-4 adverse events in the two cohorts were hand-foot syndrome (17.2%, 5/29) and lung infection (12.5%, 2/16). There was 1 patient (immune hepatitis) in cohort A and 2 patients (pulmonary infection) in cohort B leading to treatment interruption due to adverse events, and no deaths due to treatment. Conclusions: Sorafenib or lenvatinib combined with sintilimab showed a good efficacy and safety in patients with advanced hepatocellular carcinoma, the safety and tolerability profiles were consistent with those previously observed. Sorafenib plus sintilimab provided an improved PFS versus lenvatinib, which requires a large sample of randomized controlled trial to confirm.[Table: see text]

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

2017 ◽  
Vol 35 (6) ◽  
pp. 611-617 ◽  
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.

Phase II Trial of the Combination of Bevacizumab and Erlotinib in Patients Who Have Advanced Hepatocellular Carcinoma

2009 ◽  
Vol 27 (6) ◽  
pp. 843-850 ◽  
Author(s):  
Melanie B. Thomas ◽  
Jeffrey S. Morris ◽  
Romil Chadha ◽  
Michiko Iwasaki ◽  
Harmeet Kaur ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Response Rate ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Study Objective ◽  
Advanced Hcc

Purpose The study objective was to determine the proportion of patients with hepatocellular carcinoma (HCC) treated with the combination of bevacizumab (B) and erlotinib (E) who were alive and progression free at 16 weeks (16-week progression-free survival [PFS16]) of continuous therapy. Secondary objectives included response rate, median PFS, survival, and toxicity. Patients and Methods Patients who had advanced HCC that was not amenable to surgical or regional therapies, up to one prior systemic treatment; Childs-Pugh score A or B liver function; Eastern Cooperative Oncology Group performance status 0, 1, or 2 received B 10 mg/kg every 14 days and E 150 mg orally daily, continuously, for 28-day cycles. Tumor response was evaluated every 2 cycles by using Response Evaluation Criteria in Solid Tumors Group criteria. A total of 40 patients were treated. Results The primary end point of PFS16 was 62.5%. Ten patients achieved a partial response for a confirmed overall response rate (intent-to-treat) of 25%. The median PFSevent was 39 weeks (95% CI, 26 to 45 weeks; 9.0 months), and the median overall survival was 68 weeks (95% CI, 48 to 78 weeks; 15.65 months). Grades 3 to 4 drug-related toxicity included fatigue (n = 8; 20%), hypertension (n = 6; 15%), diarrhea (n = 4; 10%) elevated transaminases (n = 4; 10%), gastrointestinal hemorrhage (n = 5; 12.5%), wound infection (n = 2; 5%) thrombocytopenia (n = 1; 2.5%), and proteinuria, hyperbilirubinemia, back pain, hyperkalemia, and anorexia (n = 1 each). Conclusion The combination of B + E in patients who had advanced HCC showed significant, clinically meaningful antitumor activity. B + E warrant additional evaluation in randomized controlled trials.

KEYNOTE-224: Phase II study of pembrolizumab in patients with previously treated advanced hepatocellular carcinoma.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. TPS504-TPS504 ◽  
Author(s):  
Andrew X. Zhu ◽  
Jennifer J. Knox ◽  
Masatoshi Kudo ◽  
Stephen L. Chan ◽  
Richard S. Finn ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Disease Progression ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Locoregional Therapy ◽  
Advanced Hepatocellular Carcinoma ◽  
Ecog Performance Status ◽  
Previously Treated

TPS504 Background: The tyrosine kinase inhibitor sorafenib is the standard of care for first-line hepatocellular carcinoma (HCC). For patients with HCC after disease progression on sorafenib or for those with intolerance to sorafenib, no approved therapies are available. Because HCC is often driven by inflammation and is also associated with a suppressed immunoenvironment, there is a strong rationale to evaluate immunotherapy in patients with this type of cancer. The single-arm, multisite, phase 2 KEYNOTE-224 study (ClinicalTrials.gov, NCT02702414) was designed to evaluate the efficacy and safety of the anti–PD-1 antibody pembrolizumab in patients with previously treated advanced HCC. Methods: Approximately 100 patients will be enrolled. Inclusion criteria include age ≥18 years, histologically or cytologically confirmed diagnosis of HCC Barcelona Clinic Liver Cancer (BCLC) stage C disease or BCLC stage B disease not amenable to or refractory to locoregional therapy, and disease not amenable to a curative treatment approach (eg, transplantation, surgery, or ablation). Patients must also have measurable disease based on RECIST v1.1 as confirmed by central imaging vendor review, documented objective radiographic progression after stopping treatment with sorafenib or intolerance to sorafenib, Child-Pugh liver score A, ECOG performance status 0-1, and predicted life expectancy > 3 months. Patients will be allocated to receive pembrolizumab 200 mg IV every 3 weeks for up to 35 cycles (~2 years) or until disease progression, unacceptable toxicity, patient withdrawal of consent, or investigator decision. Response will be assessed every 9 weeks per RECIST v1.1 by central imaging vendor review. Adverse events (AEs) will be assessed throughout treatment and for 30 days thereafter (90 days for serious AEs) and graded per NCI CTCAE v4.0. The primary end point is objective response rate per RECIST v1.1 by central imaging vendor review. Secondary end points are overall survival; safety and tolerability; and duration of response, disease control rate, time to progression, and progression-free survival per RECIST v1.1 by central imaging vendor review. Enrollment in KEYNOTE-224 is ongoing. Clinical trial information: NCT02702414.

Lenvatinib for Hepatocellular Carcinoma Patients with Nonviral Infection Who Were Unlikely to Respond to Immunotherapy: A Retrospective, Comparative Study

Oncology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Takeshi Hatanaka ◽  
Satoru Kakizaki ◽  
Tamon Nagashima ◽  
Masashi Namikawa ◽  
Takashi Ueno ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Viral Infection ◽  
Objective Response ◽  
Survival Rates ◽  
Treatment Strategies ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Infection Group ◽  
Significant Difference

<b><i>Aim:</i></b> Atezolizumab plus bevacizumab (atezo + bev) shows a good overall survival (OS) in advanced hepatocellular carcinoma (HCC) patients. However, the OS of patients with nonviral infection is quite worse than that in those with viral infection. The present study investigated the efficacy and safety of lenvatinib in patients with nonviral infection, who were unlikely to obtain benefit from atezo + bev. <b><i>Methods:</i></b> We conducted a multicenter retrospective study that included 139 advanced HCC patients treated with lenvatinib between March 2018 and September 2020. <b><i>Results:</i></b> The median age was 72 years, and 116 patients (83.5%) were male. Based on the etiology of liver disease, 84 (60.4%) and 55 patients (39.6%) were assigned to the viral infection and nonviral infection groups, respectively. The significant extents in patient characteristics were not observed in both groups. The objective response rate per mRECIST and progression-free survival (PFS) did not differ significantly between the viral infection and nonviral infection groups (36.0 vs. 33.0%, <i>p</i> = 0.85; and 7.6 vs. 7.5 months, <i>p</i> = 0.94, respectively). The 1-year survival rates were 68.7% (95% confidence interval [CI] 57.7–79.7%) in the viral infection group and 59.5% (95% CI 45.2–73.8%) in the nonviral infection group. The viral infection group was not a significant factor associated with the PFS or OS in a multivariate analysis. <b><i>Conclusions:</i></b> Lenvatinib shows no significant difference in response between patients with and without viral infection. Treatment strategies based on the etiology of liver disease may lead to good clinical outcome.

scholarly journals Second-line treatments for Advanced Hepatocellular Carcinoma: A Systematic Review and Bayesian Network Meta-analysis

2021 ◽  
Author(s):  
Antonio Giovanni Solimando ◽  
Nicola Susca ◽  
Antonella Argentiero ◽  
Oronzo Brunetti ◽  
Patrizia Leone ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Performance Status ◽  
Progression Free Survival ◽  
Controlled Trials ◽  
Advanced Hepatocellular Carcinoma ◽  
Second Line ◽  
Randomized Controlled ◽  
Meta Analyses

Abstract Background & Aims A plethora of second-line therapies have been recently introduced for hepatocellular carcinoma (HCC) treatment with promising results. A meta-analysis of second-line treatments for HCC has been performed to better tailor their use based on improved patient stratification and to identify the best available option. Methods Pubmed, Scopus, Web of Science, and ClinicalTrials.gov were searched for randomized controlled trials evaluating second-line treatment for advanced HCC in patients already treated with sorafenib. The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS) and drug withdrawal due to adverse events. Network meta-analyses were performed considering placebo as the basis for comparison in efficacy and safety analyses. Subgroup stratification considered gender, age, sorafenib-responsiveness and drug tolerability, viral infection, macrovascular invasion, HCC extrahepatic spread, performance status, and alpha-fetoprotein levels. Results Fourteen phase II or III randomized controlled trials, involving 5,488 patients and 12 regimens, were included in the analysis. Regorafenib (hazard ratio (HR) = 0.63, 95% confidence interval (CI) = 0.50–0.79), cabozantinib (HR = 0.76, 95% CI = 0.63–0.92), and ramucirumab (HR = 0.82, 95% CI = 0.70–0.76) significantly prolonged OS compared with placebo. Cabozantinib (HR = 0.44, 95% CI = 0.36–0.52), regorafenib (HR = 0.46, 95% CI = 0.37–0.56), ramucirumab (HR = 0.54, 95% CI = 0.43–0.68), brivanib (HR = 0.56, 95% CI = 0.42–0.76), S-1 (HR = 0.60, 95% CI = 0.46–0.77), axitinib (HR = 0.62, 95% CI = 0.44–0.87), and pembrolizumab (HR = 0.72, 95% CI = 0.57–0.90) significantly improved PFS compared with placebo. None of the compared drugs deemed undoubtedly superior after having performed a patients’ stratification. Conclusions The results of this network meta-analysis suggest the use of regorafenib and cabozantinib as second-line treatments in HCC.

scholarly journals Camrelizumab Plus Sorafenib Versus Sorafenib Monotherapy for Advanced Hepatocellular Carcinoma: A Retrospective Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Qinqin Liu ◽  
Nan You ◽  
Jing Li ◽  
Ke Wu ◽  
Xuehui Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Targeted Therapy ◽  
Combination Therapy ◽  
Therapy Group ◽  
Combined Therapy ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Significant Difference ◽  
Clinical Benefits

BackgroundHepatocellular carcinoma (HCC) is a highly aggressive malignancy with poor prognosis. Immunotherapy has gained great interest for various solid tumors due to its promising clinical efficacy. Targeted therapy also plays a crucial role in anticancer treatment. However, studies on the combination of immunotherapy and targeted therapy for advanced HCC are limited. Thus, the objective of this study was to investigate the efficacy and safety of camrelizumab combined with sorafenib in the treatment of advanced HCC.MethodsFrom January 2019 to January 2021, 100 consecutive patients with advanced HCC in our hospital were enrolled for this study. Patients were assigned into two groups: a combined-therapy group (camrelizumab + sorafenib) and a sorafenib-only group. Progression-free survival (PFS), overall survival (OS), treatment response, and relevant adverse effects (AEs) were evaluated and recorded.ResultsOf a total of 100 patients, 35 received a combination of camrelizumab and sorafenib, and 65 were treated with sorafenib alone. After 1:1 propensity score matching (PSM), each group had 34 patients. The overall response rate (ORR) of the combined-therapy group was statistically significantly higher than that of the sorafenib-only group (before PSM, p = 0.037; after PSM, p = 0.010). However, there was no significant difference in disease control rate (DCR) between the two groups (before PSM, p = 0.695; after PSM, p = 1.000). Patients who received the combination therapy had significantly longer PFS than those who received the sorafenib monotherapy (before PSM, p = 0.041; after PSM, p = 0.043). However, the two groups exhibited comparable median OS (before PSM, p = 0.135; after PSM, p = 0.105). Although the combined-therapy group showed a higher incidence of AEs such as thrombocytopenia than the sorafenib-only group after PSM, most of these AEs were easily controlled after treatment.ConclusionCamrelizumab plus sorafenib showed favorable efficacy and manageable toxicity for patients with advanced HCC. However, more prospective randomized trials are necessary to further verify the potential clinical benefits of this combination therapy.

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