scholarly journals Efficacy and Safety of Lenvatinib Therapy for Unresectable Hepatocellular Carcinoma in a Real-World Practice in Korea

Liver Cancer ◽  
2021 ◽  
pp. 1-11
Author(s):  
Myung Ji Goh ◽  
Joo Hyun Oh ◽  
Yewan Park ◽  
Jihye Kim ◽  
Wonseok Kang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factors ◽  
Disease Progression ◽  
Real World ◽  
Medical Center ◽  
Objective Response ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Eligibility Criteria ◽  
Unresectable Hepatocellular Carcinoma

<b><i>Background:</i></b> Lenvatinib has been recently approved as a first-line treatment option for patients with unresectable hepatocellular carcinoma (HCC) in Korea. We aimed to study the efficacy and safety of lenvatinib therapy in a real-world practice and to find prognostic factors related to survival and disease progression. <b><i>Methods:</i></b> A hospital-based retrospective study was conducted on 111 consecutive patients who had unresectable HCC and were treated with lenvatinib at Samsung Medical Center from October 2018 to March 2020. Efficacy was determined using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria in 111 patients who completed 1st tumor assessment. Safety was evaluated in 116 HCC patients including 5 patients who discontinued lenvatinib due to adverse events (AEs) before 1st tumor assessment using Common Terminology Criteria for AEs version 5.0. <b><i>Results:</i></b> A total of 111 patients with a median age of 59 years were analyzed during a median follow-up duration of 6.2 (4.4–9.0) months. The Kaplan-Meier estimate of overall survival was 10.5 months, and the median progression-free survival was 6.2 months. Based on mRECIST criteria, the objective response rate was 18.9% and disease control rate was 75.7%. AEs developed in 86/116 (74.1%) patients, and grade ≥3 AEs developed in 16/116 (13.8%) patients. Diarrhea, hand-foot skin rash, abdominal pain, hypertension, and anorexia were identified as the AEs with the highest frequencies of any grade. REFLECT eligibility criteria including tumor extent ≥50% liver occupation or inadequate bone marrow function and occurrence of anorexia were prognostic factors for survival, and occurrence of diarrhea was a favorable factor for disease progression. <b><i>Conclusion:</i></b> Lenvatinib therapy showed a favorable efficacy and safety in a real-world practice. The REFLECT eligibility criteria and specific AEs could be one of the prognostic markers.

Efficacy and safety of lenvatinib in the real-world treatment of hepatocellular carcinoma: Results from a Canadian multicenter database (HCC CHORD).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 275-275
Author(s):  
Carla Pires Amaro ◽  
Michael J Allen ◽  
Jennifer J. Knox ◽  
Erica S Tsang ◽  
Howard John Lim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Real World ◽  
Objective Response ◽  
Progression Free Survival ◽  
Drug Discontinuation ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
First Line ◽  
The Real ◽  
First Line Therapy

275 Background: The REFLECT trial establishedlenvatinib (LEN) as a first-line treatment option for hepatocellular carcinoma (HCC). Compared to sorafenib (S), LEN has a higher objective response rate (ORR) and progression-free survival (PFS) with a slightly different toxicity profile. The aim of this study was to gather data regarding the efficacy and safety of LEN when used in the real-world treatment of HCC. To our knowledge, this is the first study to examine LEN use in HCC patients treated outside of Asia. Methods: HCC patients treated with LEN from 10 cancer centers in the Canadian provinces of British Columbia, Alberta, Ontario and Nova Scotia between July 2018 to July 2020 were included. Overall survival (OS), PFS, disease control rate (DCR) and ORR were retrospectively analyzed and compared across first- and second-to-fourth line use of LEN. ORR was determined radiographically according to the treating physician´s opinion in clinical notes and not RECIST 1.1 or mRECIST. Toxicities were also examined. Results: A total of 220 patients were included in this analysis. Median age was 67 years, 80% were men and 25.5% East Asian. The most frequent causes of liver disease were hepatitis C (37%) and B (26%). 62% of patients received any localized treatment before LEN, of those 26% had TACE, 15% TARE and 7.7% had liver transplant. Before starting LEN 29% of patients were ECOG 0 and 59% were ECOG 1. Most patients were Child-Pugh A (81%) and BCLC stage C (75.5%). Main portal vein invasion was present in 14% of the patients. Median follow-up was 4.5 months. A total of 173 patients (79%) received LEN as first line therapy and 47 patients (21%) were treated in second-to-fourth line. Of patients receiving LEN in first line, 22 (13%) started treatment with S, but switched to LEN before progression due to poor tolerance of S. ORR, DCR, PFS and OS are shown in the table. Toxicities occurred in 86% of patients and led to dose reductions in 76 (35%) patients and drug discontinuation in 53 (24%) patients. The most common side effects were fatigue (59%), hypertension (41%), decreased appetite (25%) and diarrhea (22%). Conclusions: Outcomes of HCC patients treated in Canada with LEN in the first line are comparable to those demonstrated in the REFLECT trial, despite the inclusion of Child-Pugh B and ECOG >1 patients. LEN use in second or later lines also showed similar outcomes, although more conclusions are difficult to draw due to the small numbers. LEN appears to be effective and safe in real world practice outside of Asia in first- and second-to-fourth line treatment of HCC. [Table: see text]

Real-world experience of pembrolizumab plus lenvatinib in unresectable hepatocellular carcinoma in Taiwan.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16627-e16627 ◽  
Author(s):  
Chi-Jung Wu ◽  
Ya-Wen Hung ◽  
Pei_Chang Lee ◽  
ChiehJu Lee ◽  
Ming Huang Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Real World ◽  
Systemic Treatment ◽  
Checkpoint Inhibitors ◽  
Medical Center ◽  
Objective Response ◽  
Post Treatment ◽  
Advanced Hcc ◽  
Unresectable Hepatocellular Carcinoma

e16627 Background: Multi-kinase inhibitors and immune checkpoint inhibitors (ICIs) are treatment options of systemic therapy for unresectable hepatocellular carcinoma (HCC). Targeted therapy can potentially enhance T cell infiltration and activation, consequently, cooperate with ICIs to produce synergistic anti-tumor effects. The ongoing clinical trial shows promising data by combining pembrolizumab with lenvatinib for advanced HCC. The study tried to evaluate the treatment response and adverse events of pembrolizumab plus lenvatinib for HCC in real-world setting. Methods: From Jul. 2019, patients who received pembrolizumab plus lenvatinib for unresectable HCC in a tertiary medical center in Taiwan were prospectively enrolled. The status of HCC was either in advanced HCC or failed by prior locoregional treatment. The dosage of pembrolizumab was 100mg every 3 weeks. The starting dose of lenvatinib was 10mg per day then titrating to weight-based dose according to recommendation. Patients who had received at least 2 cycles of pembrolizumab were evaluated in this report. The tumor response was assessed with Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST (mRECIST). The treatment related adverse events (TRAEs) were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: Till the end of Jan. 2020, 27 patients had received at least 2 cycles of pembrolizumab, and 17 had evaluable post-treatment images either by CT or MRI. There were 6 (22.2%) in BCLC B, and 21 (77.8%) in BCLC C. Of them, 17 (63%) were treated as the first-line systemic treatment, 8 as the second-line and 2 as the third line systemic treatment. Of the 17 cases with post-treatment image studies, there were 6 (35.3%) in partial response (PR), 7 (41.2%) in stable disease (SD), and 4 (23.5%) in progressive disease (PD) by RECIST v1.1; and 1 (5.8%) in complete response (CR), 9 (52.9%) in PR, 3 (17.6%) in SD and 4 (23.5%) in PD by mRECIST, respectively. The objective response rate (ORR) and disease control rate (DCR) by mRECIST were 58.7% and 76.5%, respectively. The most common TRAEs in any grade were hypertension 24 (88.4%), palmar-plantar syndrome 19 (70.4%), hypothyroidism 19(70.4%). The Grade 3/4 TRAEs were 3 (11.1%) with psoriasis-like skin reaction, 3 (11.1%) with hypertension and 2 (7.4%) with palmar-plantar syndrome. Conclusions: Pembrolizumab plus lenvatinib can produce excellent ORR and DCR with tolerable safety profiles. Such combination could be a promising strategy for unresectable HCC in the future.

Lenvatinib plus pembrolizumab versus lenvatinib in patients with unresectable hepatocellular carcinoma: A real world study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16138-e16138
Author(s):  
I-Cheng Lee ◽  
Chi-Jung Wu ◽  
San-Chi Chen ◽  
Yee Chao ◽  
Yi-Hsiang Huang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Disease Control ◽  
Real World ◽  
Objective Response Rate ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Disease Control Rate ◽  
Recist 1.1 ◽  
Unresectable Hepatocellular Carcinoma

e16138 Background: The combination of lenvatinib (LEN) and pembrolizumab (PEMBRO) showed promising response rates and survival in a phase 1b trial for patients with unresectable hepatocellular carcinoma (HCC). Whether LEN plus PEMBRO provides better outcomes than LEN monotherapy remains unclear. The aim of this study was to compare the outcomes of LEN plus PEMBRO versus lenvatinib monotherapy in patients with unresectable HCC in the real world setting. Methods: A total of 123 patients with unresectable HCC were retrospectively enrolled, including 61 patients with LEN monotherapy and 62 patients with LEN plus PEMBRO. We evaluated progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) by RECIST 1.1 and modified RECIST (mRECIST) criteria. Results: One hundred and one (82.1%) patients were in BCLC stage C and 81 (65.9%) patients received LEN or LEN plus PEMBRO as first line setting. During a median follow-up period of 8.0 months, 71 (57.7%) and 31 (25.2%) of patients had disease progression and death, respectively. The median PFS was 8.4 and 4.9 months in the LEN plus PEMBRO and LEN monotherapy groups, respectively (p = 0.033). The median OS was not reached in the LEN-PEM group and was 17.2 months in the LEN monotherapy group (p = 0.064). Patients with LEN plus PEMBRO had higher objective response rate (ORR: 34.4% vs 23.7% by RECIST 1.1, p = 0.277; 57.4% vs 32.2% by mRECIST, p = 0.010) and higher disease control rate (83.6% vs 62.7% by RECIST 1.1, p = 0.017; 85.2% vs 62.7% by mRECIST, p = 0.009). In subgroup patients with BCLC stage C, LEN plus PEMBRO provided significantly longer PFS (9.1 vs 4.8 months, p = 0.008), higher ORR (60% vs 33.3%, p = 0.015) and higher DCR (88% vs 60.4%, p = 0.004) by mRECIST criteria. Conclusions: LEN plus PEMBRO provides significantly better ORR, DCR and PFS then LEN monotherapy for patients with unresectable HCC.

scholarly journals REFLECT—a phase 3 trial comparing efficacy and safety of lenvatinib to sorafenib for the treatment of unresectable hepatocellular carcinoma: an analysis of Japanese subset

2019 ◽  
Vol 55 (1) ◽  
pp. 113-122 ◽  
Author(s):  
Tatsuya Yamashita ◽  
Masatoshi Kudo ◽  
Kenji Ikeda ◽  
Namiki Izumi ◽  
Ryosuke Tateishi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Japanese Population ◽  
Objective Response ◽  
Dose Intensity ◽  
Progression Free Survival ◽  
Japanese Patients ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Unresectable Hepatocellular Carcinoma

Abstract Background A phase 3, multinational, randomized, non-inferiority trial (REFLECT) compared the efficacy and safety of lenvatinib (LEN) and sorafenib (SOR) in patients with unresectable hepatocellular carcinoma (uHCC). LEN had an effect on overall survival (OS) compared to SOR, statistically confirmed by non-inferiority [OS: median = 13.6 months vs. 12.3 months; hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.79–1.06], and demonstrated statistically significant improvements in progression-free survival (PFS) and the objective response rate (ORR) in the overall population. The results of a subset analysis that evaluated the efficacy and safety of LEN and SOR in the Japanese population are reported. Methods The intent-to-treat population enrolled in Japan was analyzed. Results Of 954 patients in the overall population, 168 Japanese patients were assigned to the LEN arm (N = 81) or the SOR arm (N = 87). Median OS was 17.6 months for LEN vs. 17.8 months for SOR (HR 0.90; 95% CI 0.62–1.29). LEN showed statistically significant improvements over SOR in PFS (7.2 months vs. 4.6 months) and ORR (29.6% vs. 6.9%). The relative dose intensity of LEN and SOR in the Japanese population was lower than in the overall population. Frequently observed, related adverse events included palmar-plantar erythrodysaesthesia syndrome (PPES), hypertension, decreased appetite, and proteinuria in the LEN arm, and PPES, hypertension, diarrhea, and alopecia in the SOR arm. Conclusions The efficacy and safety of LEN in the Japanese population were similar to those in the overall population of REFLECT. With manageable adverse events, LEN is a new treatment option for Japanese patients with uHCC. Trial registration ID ClinicalTrials.gov. No. NCT01761266.

scholarly journals Baseline Liver Function and Subsequent Outcomes in the Phase 3 REFLECT Study of Patients with Unresectable Hepatocellular Carcinoma

Liver Cancer ◽  
2021 ◽  
pp. 1-12
Author(s):  
Arndt Vogel ◽  
Catherine Frenette ◽  
Max Sung ◽  
Bruno Daniele ◽  
Ari Baron ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Objective Response ◽  
Progression Free Survival ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Free Survival ◽  
Unresectable Hepatocellular Carcinoma ◽  
Post Hoc ◽  
Treatment Emergent Adverse Event

<b><i>Introduction:</i></b> Baseline liver function among patients starting treatment for unresectable hepatocellular carcinoma (uHCC) impacts survival and could impact efficacy outcomes and safety profiles of treatments. This post hoc analysis of the phase 3 REFLECT study examined the efficacy and safety outcomes for lenvatinib and for sorafenib in patients with uHCC, assessed by Child-Pugh score (CPS) and albumin-bilirubin (ALBI) grade. <b><i>Methods:</i></b> Efficacy and safety were assessed in patient cohorts from REFLECT according to study entry baseline ALBI grade and CPS. <b><i>Results:</i></b> Lenvatinib treatment generally provided survival benefits in all groups. Median overall survival (OS) among patients with an ALBI grade of 1 was consistently higher than among patients with an ALBI grade of 2 for both the lenvatinib and sorafenib arms (lenvatinib: 17.4 vs. 8.6 months; sorafenib: 14.6 vs. 7.7 months, respectively). Median OS among patients with a CPS of 5 was consistently higher than among patients with a CPS of 6 (lenvatinib: 15.3 vs. 9.4 months; sorafenib: 14.2 vs. 7.9 months, respectively). Progression-free survival and objective response rates for these ALBI grades and CPS demonstrated similar patterns. Among patients who received lenvatinib and experienced a treatment-related treatment-emergent adverse event leading to withdrawal, 6.6% had an ALBI grade of 1, while 13.3% had an ALBI grade of 2, and 7.9% had a CPS of 5, while 12.1% had a CPS of 6. <b><i>Conclusions:</i></b> Better liver function at baseline, as measured by ALBI grade or CPS, may be prognostic for better survival outcomes in patients with uHCC undergoing treatment with lenvatinib or sorafenib.

scholarly journals Clinical impact of lenvatinib in patients with unresectable hepatocellular carcinoma who received sorafenib

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10382
Author(s):  
Yen-Yang Chen ◽  
Chih-Chi Wang ◽  
Yueh-Wei Liu ◽  
Wei-Feng Li ◽  
Yen-Hao Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
Previous Response ◽  
Unresectable Hepatocellular Carcinoma ◽  
Third Line

Background Lenvatinib has been approved for use in the systemic treatment for unresectable hepatocellular carcinoma (HCC). This study aimed to investigate the efficacy and safety of lenvatinib in patients with unresectable HCC who received sorafenib. Methods A total of 40 patients who received lenvatinib after sorafenib were retrospectively identified: as second line in 20 patients, third line in 10 patients, and fourth line and later lines in 10 patients. The treatment response to lenvatinib was determined in accordance with the guidelines of the modified Response Evaluation Criteria in Solid Tumors (mRECIST) every 2–3 months after commencement of lenvatinib. Results Median progression-free survival (PFS) and median overall survival (OS) of the whole population were 3.3 and 9.8 months, respectively. The objective response rate was 27.5%. Univariate and multivariate analyses showed that alpha-fetoprotein level >400 ng/mL was an independent prognostic factor of worse PFS and OS. The clinical outcomes of lenvatinib therapy as second-line, third-line, or fourth line and later line treatment were similar, and previous response to sorafenib could predict the response to subsequent lenvatinib. Most adverse events were grades 1–2, and the majority of patients tolerated the side effects. Our study confirms the efficacy and safety of lenvatinib as second-line and later line treatment for patients with unresectable HCC who received sorafenib in clinical practice.

scholarly journals Real-World Efficacy and Safety of Lenvatinib in Korean Patients with Advanced Hepatocellular Carcinoma: A Multicenter Retrospective Analysis

Liver Cancer ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 613-624 ◽  
Author(s):  
Jaekyung Cheon ◽  
Hong Jae Chon ◽  
Yeonghak Bang ◽  
Neung Hwa Park ◽  
Jung Woo Shin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Retrospective Analysis ◽  
Real World ◽  
Checkpoint Inhibitors ◽  
Clinical Trial Data ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Efficacy And Safety ◽  
First Line

Introduction/Objective: Lenvatinib demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the randomized phase III REFLECT trial. Considering the discrepancies in patients between clinical trial data and daily practice, an account of practical experience is needed. Methods: We conducted a multicenter retrospective analysis in which 3 tertiary referral centers participated. A total of 92 patients with advanced HCC treated with lenvatinib between September 2018 and January 2020 were analyzed. Results: Lenvatinib was used as the first-line therapy for 67 (72.8%) patients, and for 25 (27.2%) patients previously treated with other systemic therapy including immune checkpoint inhibitors. At the time of initiation of lenvatinib, 74 (80.4%) and 18 (19.6%) patients were classified as Child-Pugh A and B, respectively. Thirty-five patients (38.0%) had extensive disease that would have excluded them from the REFLECT trial. In the Child-Pugh A group, the response rate graded according to the Response Evaluation Criteria in Solid Tumors v1.1 was 21.1%, median progression-free survival (PFS) was 4.6 (95% confidence interval [CI] 3.1–6.1) months, and overall survival (OS) was 10.7 (95% CI 4.8–16.5) months for patients treated with first-line lenvatinib (n = 57). With second- or later-line lenvatinib (n = 17), median PFS and OS were 4.1 (95% CI 3.1–5.1) and 6.4 (95% CI 5.1–7.7) months, respectively. In the Child-Pugh B group (n = 18), median PFS and OS were 2.6 (95% CI 0.6–4.6) and 5.3 (95% CI 2.0–8.5) months, respectively. The most common grade 3–4 toxicities were hyperbilirubinemia (n = 8; 8.7%), AST elevation (n = 6; 6.5%), and diarrhea (n = 5; 5.4%) across all study patients. Conclusions: In this real-world study, lenvatinib was found to be well tolerated and effective in more heterogeneous HCC patient populations.

scholarly journals Efficacy and Safety of Transarterial Chemoembolization Combined With Anlotinib for Unresectable Hepatocellular Carcinoma: A Retrospective Study

2020 ◽  
Vol 19 ◽  
pp. 153303382096558
Author(s):  
Wenbo Guo ◽  
Song Chen ◽  
Zhiqiang Wu ◽  
Wenquan Zhuang ◽  
Jianyong Yang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Survival Rate ◽  
Transarterial Chemoembolization ◽  
Statistical Tests ◽  
Objective Response ◽  
Rank Test ◽  
P Value ◽  
Efficacy And Safety ◽  
Unresectable Hepatocellular Carcinoma ◽  
Survival Difference

Objective: This study aimed to explore the efficacy and safety of using transarterial chemoembolization (TACE) combined with anlotinib in patients with unresectable hepatocellular carcinoma, compared with TACE alone. Methods: This was a single-center study, retrospectively recruited 82 unresectable HCC patients who received either TACE alone (TA group; n = 46) or TACE combined with anlotinib (TC group; n = 36) between Jan 2018 and Jan 2019. The primary outcomes were progression-free survival (PFS) and overall survival (OS). While the secondary outcomes were the objective response rate (ORR), the disease control rate (DCR), and main complications. Log-rank test and Kaplan–Meier method was used to calculate the survival difference. All statistical tests were 2-sided and P value <0.05 were taken as statistically significant. Results: Patients in TC group had a significant higher PFS than those in TA group (7.35 months vs. 5.54 months, p = 0.035). Although 3-month survival rate in the 2 groups was not statistically different (97.2% vs. 93.5%, p = 0.627), the survival rate at 6 months and 1 year were strongly higher in TC group (83.3% vs. 56.5%, p = 0.016; 66.7% vs. 19.6%, respectively, p < 0.05). Furthermore, there was a significantly higher ORR in TC group, while no statistical difference existed in DCR. Neither treatment-related mortality nor grade 4 adverse events (AEs) occurred. However, 2 patients in TC group had grade 3 AEs (one suffered with erythra, and the other with hand-foot-skin reaction), which disappeared after prompt treatment. Conclusion: TACE combined with anlotinib is safe and may improve outcomes for unresectable HCC patients comparing with TACE alone. Randomized controlled trials are warranted to further evaluate treatment effects of anlotinib in HCC.

Efficacy and safety of anti-VEGF therapy in metastatic unresectable hepatocellular carcinoma: A meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15632-e15632
Author(s):  
Lakshmi Manogna Chintalacheruvu ◽  
Avanija Buddam ◽  
Arun Kanmanthareddy ◽  
Apar Kishor Ganti
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Adverse Effects ◽  
Disease Progression ◽  
Meta Analysis ◽  
Categorical Variables ◽  
Vegf Receptor ◽  
Efficacy And Safety ◽  
Unresectable Hepatocellular Carcinoma ◽  
Significant Difference

e15632 Background:Conventional chemotherapy has limited role in metastatic unresectable hepatocellular carcinoma (HCC). Sorafenib is currently approved for metastatic unresectable HCC. We wanted to assess the efficacy and safety of other tyrosine kinase inhibitors (TKI) targeting vascular endothelial growth factor (VEGF) receptor such as brivanib, linifanib and regorafenib in metastatic HCC. Methods: We have searched electronic databases Pubmed, Google scholar to identify published trials using brivanib, linifanib and regorafenib in HCC. The outcomes evaluated were overall survival, time to disease progression (TTDP) and adverse effects. Hazard ratios (HR) with their respective 95% confidence intervals (CI) were then computed using the appropriate model for categorical variables. We used STATA 13.0 and Comprehensive Meta Analysis 2.0 software for all analyses. Results: We included seven randomized control studies. A combined analysis of these seven randomised control trials showed improved overall survival (OS) in VEGF-TKI group when compared to placebo HR - 0.79; (95% CI 0.62-1.00). However, there was no significant survival benefit of the newer VEGF receptor inhibitors when compared to sorafenib (HR - 1.05; 95% CI 0.95-1.17). The time to disease progression (TTDP) was significantly better in VEGF-TKI group as compared to placebo (HR - 0.61; 95% CI 0.39-0.97). However, there was no significant difference in TTDP between VEGF-TKI group and Sorafenib (HR - 0.88; 95% CI 0.66-1.16). Adverse effects were noted to be higher in VEGF-TKI group when compared to placebo (HR- 1.07; 95% CI 1.01-1.13). Conclusions: Treatment with TKI targeting VEGF receptor is associated with a significant improvement in OS and TTDP with tolerable side effect profile. Inhibiting the VEGF receptor pathway could lead to improved outcomes in HCC.

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.

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