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 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 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.

The efficacy and safety of lenvatinib in patients with intermediate-stage hepatocellular carcinoma: A nationwide multicenter study in Japan.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 548-548
Author(s):  
Kaoru Tsuchiya ◽  
Masayuki Kurosaki ◽  
Azusa Sakamoto ◽  
Hiroyuki Marusawa ◽  
Chikara Ogawa ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Multicenter Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Intermediate Stage ◽  
Median Number ◽  
Observation Time ◽  
Efficacy And Safety ◽  
Free Survival ◽  
Modified Recist

548 Background: Lenvatinib (LEN) has been used in patients with unresectable hepatocellular carcinoma (u-HCC) since Mar 2018 in Japan. We conducted a nationwide multicenter study and especially focused on the efficacy and safety in the patients with intermediate-stage u-HCC. Methods: A total of 240 patients received LEN from March 2018 at 15 sites in Japan was enrolled. Tumour assessments in accordance with modified RECIST were done using dynamic CT or MRI within 4-8 weeks and every 6-8 weeks thereafter. Results: In this study, 88 of 240 (36.7%) patients were BCLC stage B. Among them 76 (86.3%) patients received TACE before LEN and the median number of TACE was 2 (1-10). Only 4 patients were TKI experienced and other 84 (95.5%) patients received LEN as a 1st line therapy. The median pretreatment ALBI score was -2.35 and 75 (85.2%) patients were Child-Pugh A. In this cohort, 73 (83.0%) patients were beyond up-to-seven criteria and the median pretreatment AFP was 38.2 (2-12870) ng/mL. The median observation time was 8.5 months and 16 patients died. The median progression free survival was 8.7 months, and the median overall survival (OS) was not reached. Objective response rate (ORR) and disease control rate (DCR) were 48.5% and 80.3%. AFP decrease ( > 20%) after 1 month was observed in 52 (59.0%) patients. Child-Pugh B patients (n = 13) had significantly shorter OS than Child-Pugh A (p = 0.02) and median OS in Child-Pugh B patients was 8.8 months. The patients received > 6 times TACE before LEN had significantly shorter OS than patients received ≤ 6 times TACE (p = 0.02). Additional TACE was performed in 8 patients and The median time of restarting LEN was 19 days. The median ALBI score before additional TACE, Day 1 after TACE and Day 28 after TACE were -2.38, -2.07, and -2.36.There was no severe adverse event associated with additional TACE. The median duration of LEN in patients treated with LEN and additional TACE was 8.5 months. Conclusions: The ORR and DCR of LEN in Child-Pugh A patients with intermediate-stage HCC were 46.6% and 79.3%. The therapeutic strategies for intermediate-stage HCC should be discussed based on the liver function, tumor states, and treatment course about TACE.

scholarly journals CalliSpheres Drug-Eluting Bead Transcatheter Arterial Chemoembolization Presents With Better Efficacy and Equal Safety Compared to Conventional TACE in Treating Patients With Hepatocellular Carcinoma

2019 ◽  
Vol 18 ◽  
pp. 153303381983075 ◽  
Author(s):  
Hua Xiang ◽  
Lin Long ◽  
Yuanhui Yao ◽  
Zhiyong Fang ◽  
Zhiming Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Liver Function ◽  
Transcatheter Arterial Chemoembolization ◽  
Response Rate ◽  
Objective Response ◽  
Progression Free Survival ◽  
Free Survival ◽  
Drug Eluting ◽  
Arterial Chemoembolization

The aim of this study was to compare the treatment response, survival, liver function, and adverse event incidence of drug-eluting bead transcatheter arterial chemoembolization using CalliSpheres microspheres with conventional transcatheter arterial chemoembolization in patients with hepatocellular carcinoma. Seventy-three patients with hepatocellular carcinoma who received drug-eluting bead transcatheter arterial chemoembolization (using CalliSpheres microspheres) or conventional transcatheter arterial chemoembolization treatment were consecutively enrolled. Treatment response was assessed by modified Response Evaluation Criteria in Solid Tumors at month 1/month 3/month 6; posttreatment, liver function indexes, and adverse events were recorded. Progression-free survival and overall survival were also calculated. Objective response rate of patients at months 1, 3, and 6, disease control rate of patients and objective response rate of nodules at month 3 were increased in drug-eluting bead transcatheter arterial chemoembolization group compared with conventional transcatheter arterial chemoembolization group. In addition, drug-eluting bead transcatheter arterial chemoembolization using CalliSpheres microspheres was an independent factor for predicting better objective response rate at month 1. Patients in drug-eluting bead transcatheter arterial chemoembolization group achieved longer progression-free survival and similar overall survival compared to those in conventional transcatheter arterial chemoembolization group; Cox proportional hazards regression model analyses revealed that drug-eluting bead transcatheter arterial chemoembolization using CalliSpheres microspheres was associated with better progression-free survival while it did not affect overall survival. Meanwhile, most of the occurrences of abnormal liver function indexes were similar between 2 groups, whereas drug-eluting bead transcatheter arterial chemoembolization group had a higher percentage of patients with total bile acid ≥2 upper limit of normal compared to conventional transcatheter arterial chemoembolization group at month 1. Moreover, the adverse event incidences between 2 groups were similar. In conclusion, drug-eluting bead transcatheter arterial chemoembolization using CalliSpheres microspheres achieves better treatment response and progression-free survival while equal safety compared to conventional transcatheter arterial chemoembolization in patients with hepatocellular carcinoma.

scholarly journals The Efficacy of TACE Combined With Lenvatinib Plus Sintilimab in Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Fei Cao ◽  
Yi Yang ◽  
Tongguo Si ◽  
Jun Luo ◽  
Hui Zeng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Once Daily ◽  
Free Survival ◽  
Unresectable Hepatocellular Carcinoma ◽  
Primary Endpoints ◽  
Duration Of Response ◽  
Modified Recist

ObjectiveTo assess the efficacy and safety of transarterial Chemoembolization (TACE) combined with lenvatinib plus sintilimab in unresectable hepatocellular carcinoma (HCC).Patients and MethodsThe data of patients with unresectable HCC administered a combination therapy with TACE and lenvatinib plus sintilimab were retrospectively assessed. Patients received lenvatinib orally once daily 2 weeks before TACE, followed by sintilimab administration at 200 mg intravenously on day 1 of a 21-day therapeutic cycle after TACE. The primary endpoints were objective response rate (ORR) and duration of response (DOR) by the modified RECIST criteria.ResultsMedian duration of follow-up was 12.5 months (95%CI 9.1 to 14.8 months). ORR was 46.7% (28/60). Median DOR in confirmed responders was 10.0 months (95%CI 9.0-11.0 months). Median progression-free survival (PFS) was 13.3 months (95%CI 11.9-14.7 months). Median overall survival (OS) was 23.6 months (95%CI 22.2-25.0 months).ConclusionsTACE combined with lenvatinib plus sintilimab is a promising therapeutic regimen in unresectable hepatocellular carcinoma.

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.

Clinical Outcomes of 2nd- and 3rd-Line Regorafenib for Advanced Hepatocellular Carcinoma

Oncology ◽  
2021 ◽  
pp. 1-8
Author(s):  
Kensuke Naruto ◽  
Tomokazu Kawaoka ◽  
Kei Amioka ◽  
Yutaro Ogawa ◽  
Kikukawa Chihiro ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Outcomes ◽  
Median Overall Survival ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Free Survival ◽  
Line Therapy ◽  
Unresectable Hepatocellular Carcinoma

<b><i>Introduction:</i></b> This study compared clinical outcomes of 2nd- and 3rd-line regorafenib in patients with unresectable hepatocellular carcinoma. <b><i>Methods:</i></b> In this retrospective cohort study, 48 patients were treated with regorafenib for unresectable hepatocellular carcinoma. Thirty-five and 13 patients were initiated on 2nd- and 3rd-line therapy, respectively. We assessed the responses to and safety of the therapy. <b><i>Results:</i></b> There were no statistically significant differences in clinical characteristics at the start of 2nd- or 3rd-line regorafenib therapy. The overall response rate of 2nd- and 3rd-line regorafenib was 20 and 8%, respectively. The disease control rate was 57 and 54%, respectively. Median overall survival (mOS) from the start of 2nd-line regorafenib was 17.5 months. mOS from the start of 3rd-line regorafenib was not obtained. Median progression-free survival of 2nd- and 3rd-line regorafenib was 4.9 and 2.3 months, respectively. mOS from 1st-line therapy with tyrosine kinase inhibitor plus sorafenib-regorafenib-lenvatinib was 29.5 months; that with lenvatinib-sorafenib-regorafenib was not obtained. Patients on 3rd-line therapy tended to have better Child-Pugh scores and tumor factors at the start of 1st-line therapy than other patients. <b><i>Conclusion:</i></b> Patients on 2nd- and 3rd-line regorafenib showed favorable responses. Good Child-Pugh scores and tumor factors may be associated with a better response rate and OS.

Safety, tolerability and efficacy of transarterial chemoembolization using anthracyclines-loaded drug eluting microspheres for treatment of patients with unresectable hepatocellular carcinoma: Pooled analyses.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 287-287
Author(s):  
Thierry De Baere ◽  
Filipe Veloso Gomes ◽  
Gontran Verset ◽  
Gerardo Tovar-Felice ◽  
Katerina Malagari ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Function ◽  
Transarterial Chemoembolization ◽  
Tumor Response ◽  
Objective Response ◽  
Progression Free Survival ◽  
Close Monitoring ◽  
Bridge To Transplant ◽  
Level Data ◽  
Drug Eluting

287 Background: Transarterial chemoembolization either with Lipiodol (cTACE) or with drug eluting microspheres (DEM-TACE) is indicated for the treatment of hepatocellular carcinoma (HCC) not amenable to curative treatments in patients with preserved liver function. Safety of TACE is becoming more important with its increased use as a bridge to transplant or downstaging to resection, but also for preservation of liver function in case of subsequent immuno-combination therapies. LifePearl microspheres is a novel DEM comprised of polyethylene-glycol with reported good safety profile and efficacy in smaller series. Our purpose was to assess safety and efficacy of TACE using anthracycline loaded LifePearl for the treatment of patients with unresectable HCC in a pooled analysis of studies with available more than 500 patient’s level data. Methods: We pooled patient level data from 5 single arm studies. Safety was assessed by close monitoring of adverse events according to CTCAE (v4.03). Tumor response was assessed, according to mRECIST and RECIST1.1 and analyzed as best overall response to account for differences in time of imaging follow-up between studies. The Kaplan-Meier method was used to estimate event rates for time to event outcomes: progression free survival (PFS), time to unTACEable progression (TTUP) and overall survival (OS) censoring patients at time of surgery or transplantation. Results: Out of 586 patients, 85.5%, 13.5% and 1.0% were Child Pugh A, B and C, respectively. BCLC stages 0, A, B and C were 13.6%, 43.4%, 41.1% and 1.9% respectively. The mean number of HCC lesions was 2.1±1.5 and mean sum of tumor diameters was 49.3±32.9mm. In 19% of patients alpha-feto protein level was > 200ng/ml. A mean of 1.9±1.3 DEM-TACEs were performed per patient. A total of 197 events were reported including 2.6 % grade 4 and 1.5% grade 5, mostly related to post-embolization syndrome. Complete response, partial response and stable disease were 60.2%, 27.1% and 7.4% respectively providing an objective response and disease control rates of 87,3% and 94,7% respectively. 10% of patients were transplanted or resected. Median OS, PFS and TTUP is indicated in the table below. OS was 89.2%, 80.2% and 69.7% at 12, 18 and 24 months respectively. Conclusions: The treatment of patients with unresectable HCC with anthracycline loaded LifePearl showed good tolerance with acceptable toxicity and high tumor response rate that translated into promising PFS, TTUP and OS. [Table: see text]

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]

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