Trial reportLancet (London, England)2018
Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial.
Trial report in Lancet (London, England), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 29 registered trials, which are not on this map. Cited by 3,396 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multicenter, Randomized, Open-Label, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib (E7080) Versus Sorafenib in First-Line Treatment of Subjects With Unresectable Hepatocellular Carcinoma
A Prospective Cohort Study of the Effect of Lenvatinib Combined With TACE in Preventing the Recurrence in High-risk Patients With Hepatocellular Carcinoma
Lenvatinib Combined Pembrolizumab as a Second-line Treatment in Advanced Hepatobiliary Tumors: a Single-center, Single-arm, Non-randomized Clinical Study
Transarterial Chemoembolization With Lenvatinib Versus Lenvatinib Alone in First-line Treatment of Advanced Hepatocellular Carcinoma: a Phase III, Multicenter, Randomized Controlled Trial
a Single-arm Study of Combined Therapy Using Oxaliplatin and Gemcitabine Chemotherapy, Lenvatinib and Programmed Cell Death Protein 1 Antibody (JS001) for Patients With Advanced and Unresectable Intrahepatic Cholangiocarcinoma
An Exploratory Study of Sorafenib Plus Toripalimab for Unresectable Hepatocellular Carcinoma With Portal Vein Tumor Thrombus
Toripalimab Plus Lenvatinib as Second-line Treatment in Advanced Biliary Tract Cancers: a Single-arm, Non-randomized, Single-center Clinical Trial and Biomarker Study
Safety and Efficacy of Lenvatinib as an Adjuvant Therapy in Patients With Hepatocellular Carcinoma Following Radical Resection: A Single-Arm and Open-Label Prospective Study
Drug-eluting Bead Transarterial Chemoembolization Plus Lenvatinib or Sorafenib or PD-1 Inhibitor for Unresectable Hepatocellular Carcinoma: a Multicentric Prospective Study
A Randomized, Open, Two-cohort Phase 2 Study of Toripalimab(PD1) Combined With Lenvatnib, or Gemox Chemotherapy Combined With Lenvatinib as First-line Therapy in Patients With Advanced or Unresectable Intrahepatic Cholangiocarcinoma
Lenvatinib Combined Toripalimab in Advanced Hepatocellular Carcinoma: a Single-center, Single-arm, Non-randomized Clinical Study
Adjuvant Lenvatinib Prevents Recurrence of High-risk Patients With Hepatitis B Virus-related Hepatocellular Carcinoma Following Liver Transplantation: a Retrospective Case Control Study
A Single-arm, Non-randomized, Single-center Study to Evaluate Lenvatinib in Combination With Camrelizumab as First-Line Therapy in Patients With Advanced Hepatocellular Carcinoma
Combined Therapy Using Cisplatin and Gemcitabine Chemotherapy and Lenvatinib for Patients With Unresectable Intrahepatic Cholangiocarcinoma, a Single-arm Study
The Efficacy and Safety of Lenvatinib in Patients With Previously Treated Advanced Biliary Tract Cancer
Efficacy and Safety of PD-1 Antibody and Lenvatinib Plus TACE on Downstaging Hepatocellular Carcinoma With BCLC B/C
Regorafenib Combined With PD-1 Inhibitor Therapy for Second-line Treatment of Hepatocellular Carcinoma: A Single Arm, Nonrandomized, Single Center Clinical Study
Lenvatinib in Neo-adjuvant and Adjuvant Therapy for Poor-prognosis BCLC A HepatoCellular Carcinoma Treated by Percutaneous Ablation Procedure in a Curative Intent: Multicentre Pilot Therapeutic Trial
Hepatic Arterial Infusion Chemotherapy Combine With Lenvatinib and PD-1 Inhibitors for Advanced Hepatocellular Carcinoma With Portal Vein Tumor Thrombosis.
Neoadjuvant HAIC of TACE Plus Donafenib in BCLC B Stage Hepatocellular Carcinoma Out Up-to-seven: a Multi-center Randomized Controlled Trial.
Neoadjuvant Combination Therapy of Lenvima Plus Transcatheter Arterial Chemoembolization (TACE) for Transplant-Eligible Patients With Large Hepatocellular Carcinoma
Investigation of Predictive Biomarkers in Patients With Advanced Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab
Biomarker Discovery Through Multiomics Study in Advanced Hepatocellular Carcinoma Patients Who Received Atezolizumab and Bevacizumab Combination Therapy
A Prospective Cohort Study of Single Agent Memantine in Patients With Child-Pugh Score ≥ B7 Cirrhosis and Hepatocellular Carcinoma
Multicenter Phase 2 Trial of Lenvatinib in Patients With Unresectable or Metastatic Hepatocellular Carcinoma After Progression on First-line Atezolizumab Plus Bevacizumab
The Safety and Efficacy of Hepatic Arterial Infusion Chemotherapy (HAIC) Combine Tislelizumab and Lenvatinib in the Treatment of Hepatocellular Carcinoma (HCC) With Type IV(Vp4) Portal Vein Tumor Thrombus (PVTT): A Prospective, Single-armed, Stage II Clinical Trial
Radiotherapy Delays Second-line Drug Therapy for Oligo Progressive Primary Liver Cancer: a Multicenter, Single-arm, Phase II Clinical Trial.
A Phase 2, Single Arm Study of Cabozantinib in Patients With Hepatocellular Carcinoma Who Have Received Prior Atezolizumab and Bevacizumab
A Phase 2, Multicenter, Randomized, Open-label Study Comparing Fostrox + Lenvatinib vs. Lenvatinib in Patients With Locally Advanced or Unresectable Advanced Hepatocellular Carcinoma (HCC) Who Have Received First-line Combination Immunotherapy
Who cites it
3,396 citing papers in PubMed, 5 syntheses or guidelines pooled it, 5,305 citations in OpenAlex.
- Systematic meta-analysis of the toxicities and side effects of the targeted drug lenvatinib.Annals of medicine · 2026Pooled it
- Hepatocellular carcinoma with macrovascular invasion: Review and survival meta-analysis of initial local therapy using minimal prognostic criteria.Hepatology (Baltimore, Md.) · 2026Pooled it
- Pathological and Perioperative Outcomes of Conversion Hepatectomy After Contemporary Combination Downstaging for Initially Unresectable Hepatocellular Carcinoma: A Systematic Review.Current oncology (Toronto, Ont.) · 2026Pooled it
- Comparative efficacy of immune checkpoint inhibitor-based regimens versus tyrosine kinase inhibitors in advanced hepatocellular carcinoma stratified by etiology: a systematic review and meta-analysis.International journal of clinical oncology · 2026Pooled it
- Efficacy and safety of immune-based combinations in metastatic hepatocellular carcinoma: a systematic review and network meta-analysis.BMC cancer · 2026Pooled it
- A Phase Ib/IIa Study of Fostrox in Combination with Lenvatinib as Second-line Therapy in Patients with Advanced Hepatocellular Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Durvalumab plus HAIC-FOLFOX followed by maintenance durvalumab for hepatocellular carcinoma with major portal invasion: phase 2 DurHope study.Nature communications · 2026Trial
- HILL: the efficacy and safety of hepatic arterial infusion chemotherapy with the FOLFOX regimen combined with lenvatinib and the PD-L1 inhibitor durvalumab in unresectable hepatocellular carcinoma: a prospective, single-arm, phase 2 clinical trial.Signal transduction and targeted therapy · 2026Trial
- Camrelizumab Plus Famitinib in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Phase 2 Study.Cancer medicine · 2026Trial
- Lenvatinib potentiates the antitumor efficacy of combined radiotherapy and PD-L1 blockade in lung adenocarcinoma.Cancer biology & therapy · 2026Article
- Patient characteristics to guide personalized treatment decisions and prognostication in hepatocellular carcinoma.Hepatic oncology · 2026Review
- Systemic treatment paradigms for unresectable and advanced hepatocellular carcinoma in Europe.The Lancet regional health. Europe · 2026Review
- Inhibition of ACSS2 enhances cabozantinib sensitivity by blocking TFEB-induced autophagic flux in hepatocellular carcinoma.British journal of cancer · 2026Article
- Observational
- FGFR pathway inhibition enhances PD-1 blockade and modulates antitumor immunity in colorectal cancer models.BMC cancer · 2026Article
- Prediction of treatment response and survival in patients with advanced hepatocellular carcinoma receiving sorafenib: pretreatment prognostic scores.Journal of the Egyptian National Cancer Institute · 2026Article
- Cancer-associated fibroblasts in therapeutic resistance of hepatocellular carcinoma: evidence, mechanisms, and translational implications.Medical oncology (Northwood, London, England) · 2026Review
- Combining antiviral therapy with cancer treatment in HBV-associated HCC: A translational approach.Virus research · 2026Review
- Prediction of Response to Immunotherapy in Hepatocellular Carcinoma: Where Do We Stand?Cancers · 2026Review
- Clinical impact of salvage hepatectomy for local recurrence of hepatocellular carcinoma after radiofrequency ablation or selective transarterial chemoembolization.International journal of clinical oncology · 2026Article
3,336 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors at 17 institutions in 12 countries.
Funding
Abstract
backgroundIn a phase 2 trial, lenvatinib, an inhibitor of VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor α, RET, and KIT, showed activity in hepatocellular carcinoma. We aimed to compare overall survival in patients treated with lenvatinib versus sorafenib as a first-line treatment for unresectable hepatocellular carcinoma.
methodsThis was an open-label, phase 3, multicentre, non-inferiority trial that recruited patients with unresectable hepatocellular carcinoma, who had not received treatment for advanced disease, at 154 sites in 20 countries throughout the Asia-Pacific, European, and North American regions. Patients were randomly assigned (1:1) via an interactive voice-web response system-with region; macroscopic portal vein invasion, extrahepatic spread, or both; Eastern Cooperative Oncology Group performance status; and bodyweight as stratification factors-to receive oral lenvatinib (12 mg/day for bodyweight ≥60 kg or 8 mg/day for bodyweight <60 kg) or sorafenib 400 mg twice-daily in 28-day cycles. The primary endpoint was overall survival, measured from the date of randomisation until the date of death from any cause. The efficacy analysis followed the intention-to-treat principle, and only patients who received treatment were included in the safety analysis. The non-inferiority margin was set at 1·08. The trial is registered with ClinicalTrials.gov, number NCT01761266.
findingsBetween March 1, 2013 and July 30, 2015, 1492 patients were recruited. 954 eligible patients were randomly assigned to lenvatinib (n=478) or sorafenib (n=476). Median survival time for lenvatinib of 13·6 months (95% CI 12·1-14·9) was non-inferior to sorafenib (12·3 months, 10·4-13·9; hazard ratio 0·92, 95% CI 0·79-1·06), meeting criteria for non-inferiority. The most common any-grade adverse events were hypertension (201 [42%]), diarrhoea (184 [39%]), decreased appetite (162 [34%]), and decreased weight (147 [31%]) for lenvatinib, and palmar-plantar erythrodysaesthesia (249 [52%]), diarrhoea (220 [46%]), hypertension (144 [30%]), and decreased appetite (127 [27%]) for sorafenib.
interpretationLenvatinib was non-inferior to sorafenib in overall survival in untreated advanced hepatocellular carcinoma. The safety and tolerability profiles of lenvatinib were consistent with those previously observed.
fundingEisai Inc.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.