# Lenvatinib

Source: https://onco.cc/drugs/lenvatinib/  
OnCo record `lenvatinib` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

An oral anti-angiogenic pill that matched sorafenib in liver cancer with higher response rates, and partners with pembrolizumab in kidney and endometrial cancer.

## Summary

REFLECT (2018): non-inferior OS (13.6 vs 12.3 months) with better PFS and ORR than sorafenib in first-line HCC. LEAP-002 (with pembrolizumab) missed its OS endpoint versus lenvatinib alone; LEAP-012 (with pembrolizumab plus TACE) improved PFS but not OS. Also approved in thyroid cancer, RCC (with everolimus or pembrolizumab) and endometrial cancer (with pembrolizumab). Hypertension, proteinuria and weight loss are dose-limiting.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-07
- Brand: Lenvima
- Modality: Small-molecule multi-kinase inhibitor (VEGFR, FGFR, PDGFR, RET, KIT)
- Mechanism: Oral inhibitor of VEGFR1-3, FGFR1-4, PDGFR-α, RET and KIT.
- Approvals: US 2015: Radioiodine-refractory thyroid cancer; US 2018: First-line unresectable HCC; US 2021: Advanced RCC with pembrolizumab; endometrial cancer with pembrolizumab; US 2016: Advanced RCC with everolimus after anti-angiogenic therapy
- Dosing: Oral; 12 mg daily (≥60 kg) or 8 mg daily (<60 kg) in HCC
- Toxicity (grade 3+): Hypertension 23%; Diarrhoea 4%; Decreased appetite/weight loss 5%; Proteinuria 6%

## Notes

- In kidney cancer: CLEAR (with pembrolizumab) produced the longest first-line PFS reported, 23.9 months, with OS HR 0.79; lenvatinib plus everolimus is used in later lines (Study 205). The dose is 20 mg daily with pembrolizumab or 18 mg with everolimus 5 mg, about 70 percent of CLEAR patients needed a reduction, and 82 percent had a grade 3 or higher event.
- In endometrial cancer: approved with pembrolizumab for pMMR advanced disease after platinum (KEYNOTE-775, OS 18.3 versus 11.4 months), after accelerated approval on KEYNOTE-146 in 2019; LEAP-001 in first line against chemotherapy was negative. The dose is 20 mg daily with pembrolizumab 200 mg every 3 weeks; hypertension affected 64 percent (38 percent grade 3 or higher), hypothyroidism 57 percent, diarrhoea 54 percent, and about 67 percent of KEYNOTE-775 patients needed a dose reduction. Blood pressure is checked weekly for two cycles and TSH every 6 weeks.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Lenvatinib
- FDA label (DailyMed): https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Lenvatinib

## Connected records

- biomarkers: [MSI-high (microsatellite instability by PCR or sequencing)](https://onco.cc/biomarkers/msi-high/)
- cancers: [Adenoid cystic carcinoma](https://onco.cc/cancers/adenoid-cystic-carcinoma/), [Advanced hepatocellular carcinoma (BCLC C)](https://onco.cc/cancers/hcc-advanced/), [Advanced or recurrent endometrial cancer](https://onco.cc/cancers/advanced-recurrent-endometrial-cancer/), [Anaplastic thyroid cancer](https://onco.cc/cancers/anaplastic-thyroid-cancer/), [Chromophobe renal cell carcinoma](https://onco.cc/cancers/chromophobe-rcc/), [Clear cell renal cell carcinoma](https://onco.cc/cancers/clear-cell-rcc/), [Endometrial cancer](https://onco.cc/cancers/endometrial/), [Endometrial cancer with no specific molecular profile](https://onco.cc/cancers/endometrial-nsmp/), [Follicular thyroid cancer](https://onco.cc/cancers/follicular-thyroid-cancer/), [Hepatocellular carcinoma](https://onco.cc/cancers/hcc/), [Intermediate hepatocellular carcinoma (BCLC B)](https://onco.cc/cancers/hcc-intermediate/), [Papillary thyroid cancer](https://onco.cc/cancers/papillary-thyroid-cancer/), [Renal cell carcinoma](https://onco.cc/cancers/rcc/), [Salivary gland cancers](https://onco.cc/cancers/salivary-gland/), [Thymic carcinoma](https://onco.cc/cancers/thymic-carcinoma/), [Thymoma (WHO types A, AB, B1, B2 and B3)](https://onco.cc/cancers/thymoma/), [Thymoma and thymic carcinoma](https://onco.cc/cancers/thymic-epithelial/), [Thyroid cancer](https://onco.cc/cancers/thyroid/), [Uterine carcinosarcoma](https://onco.cc/cancers/uterine-carcinosarcoma/)
- technologies: [Anti-angiogenic therapy](https://onco.cc/technologies/antiangiogenic/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [FGFR2](https://onco.cc/targets/fgfr2/), [KIT](https://onco.cc/targets/kit/), [RET](https://onco.cc/targets/ret/), [VEGF / VEGFR](https://onco.cc/targets/vegf/)
- companies: [Eisai](https://onco.cc/companies/eisai/), [GI Innovation](https://onco.cc/companies/gi-innovation/), [Merck & Co. (MSD)](https://onco.cc/companies/merck/)
- pathways: [Endometrial cancer (KEGG map)](https://onco.cc/pathways/endometrial-cancer-signalling/), [Hepatocellular carcinoma (KEGG map)](https://onco.cc/pathways/hepatocellular-carcinoma-signalling/), [Renal cell carcinoma (KEGG map)](https://onco.cc/pathways/renal-cell-carcinoma-signalling/), [The angiogenic switch & tumour vessels](https://onco.cc/pathways/angiogenic-switch/), [Thyroid cancer (KEGG map)](https://onco.cc/pathways/thyroid-cancer-signalling/), [VEGF angiogenesis](https://onco.cc/pathways/vegf-angiogenesis/)
- terms: [Anti-VEGF class toxicities (hypertension, proteinuria, bleeding, perforation)](https://onco.cc/terms/antiangiogenic-toxicities/), [Hand-foot syndrome and hand-foot skin reaction](https://onco.cc/terms/hand-foot-syndrome/), [Radioiodine therapy (I-131)](https://onco.cc/terms/radioiodine-term/), [TACE (transarterial chemoembolisation)](https://onco.cc/terms/tace-term/), [Tyrosine kinase inhibitor (TKI)](https://onco.cc/terms/tki-term/)
- trials: [A Phase I/II Study of LM-2417 in Subjects With Advanced Solid Tumours](https://onco.cc/trials/nct06682780/), [A Phase II Study of Adjuvant Durvalumab Combined With GEMOX/GC Chemotherapy Followed by Lenvatinib Versus Capecitabine in Biliary Tract Cancer.](https://onco.cc/trials/nct07679399/), [A Phase IIb Randomized Clinical Trial of Immune Checkpoint Inhibitor-based Maintenance Therapy in Patients With Advanced Biliary Tract Cancer](https://onco.cc/trials/nct07269158/), [A Randomized, Two-cohort, Prospective Phase II Clinical Study of the Second-line Treatment of Advanced Biliary System Tumors With Liposomal Irinotecan (II) Combination Regimen](https://onco.cc/trials/nct07099794/), [A Study of AK104+Lenvatinib in Combination With Transarterial Chemoembolization (TACE) Versus TACE in Participants With Incurable/Non-metastatic Hepat](https://onco.cc/trials/nct06371157/), [A Study of BL-B01D1+TKI±Pembrolizumab in Patients With Locally Advanced or Metastatic Renal Cancer](https://onco.cc/trials/nct06962787/), [A Study of E7386 in Combination With Other Anticancer Drug(s) in Participants With Solid Tumor](https://onco.cc/trials/nct04008797/), [A Study of Nofazinlimab (CS1003) in Subjects With Advanced Hepatocellular Carcinoma](https://onco.cc/trials/nct04194775/), [A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, vs Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012)-China Extension Study](https://onco.cc/trials/nct05899049/), [A Study to Evaluate Investigational Agents With or Without Pembrolizumab (MK-3475) in Participants With Advanced Esophageal Cancer Previously Exposed to Programmed Cell Death 1 Protein (PD-1)/ Programmed Cell Death Ligand 1 (PD-L1) Treatment (MK-3475-06B)](https://onco.cc/trials/nct05319730/), [A Study to Evaluate the Safety, Tolerability, and Efficacy of MORAb-202 (Herein Referred to as Farletuzumab Ecteribulin), a Folate Receptor Alpha (FRα)-Targeting Antibody-drug Conjugate (ADC) in Participants With Selected Tumor Types](https://onco.cc/trials/nct04300556/), [An Exploratory Study on the Use of Ivosidenib for the Precise Treatment of Advanced Biliary Tract Malignancies With IDH1 Mutations in the Later Line of Therapy.](https://onco.cc/trials/nct07282262/), [CLEAR (KEYNOTE-581)](https://onco.cc/trials/clear/), [Cryoablation Combined With QL1706 (Iparomlimab/Tuvonralimab) Plus Lenvatinib in Patients With Advanced Biliary Tract Cancer.](https://onco.cc/trials/nct07829874/), [Disitamab Vedotin Plus Lenvatinib and PD-1 Inhibitors for Treating HER2-positive Advanced Biliary Tract Cancer](https://onco.cc/trials/nct07159217/), [Durvalumab and Tremelimumab With Lenvatinib as First-line Treatment in Patients With Unresectable Hepatocellular Carcinoma](https://onco.cc/trials/nct07081633/), [Efficacy and Safety of Nab-paclitaxel-Lenvatinib-Pembrolizumab as Second-line Treatment in Advanced NSCLC Patients](https://onco.cc/trials/nct06028633/), [EMERALD-3](https://onco.cc/trials/emerald-3/), [Extension Study for Participants in Studies That Include Belzutifan (MK-6482-043/LITESPARK-043)](https://onco.cc/trials/nct07405164/), [Gem+Nab-P+LEN+TIS for Advanced Unresectable BTC (GALENT-BT)](https://onco.cc/trials/nct06963060/), [GI-101/GI-101A as a Single Agent or in Combination With Pembrolizumab or Lenvatinib in Advanced Solid Tumors](https://onco.cc/trials/nct04977453/), [HAIC+Adebrelimab+Lenvatinib for Conversion Treatment of Potentially Resectable, Locally Advanced Biliary Tract Cancer](https://onco.cc/trials/nct06389500/), [Hepatic Arterial Infusion Chemotherapy Plus Envafolimab and Lenvatinib for First-Line Unresectable Advanced Biliary Tract Cancer](https://onco.cc/trials/nct07636798/), [HIM Typing Guides the Treatment of Advanced First-Line Triple-Negative Breast Cancer](https://onco.cc/trials/nct06849492/), [Iparomlimab and Tuvonralimab Injection Combined With GemOX and Lenvatinib as Conversion Therapy for Initially Potentially Resectable Intrahepatic Cholangiocarcinoma and Gallbladder Cancer](https://onco.cc/trials/nct07263360/), [KEYNOTE-775 / Study 309](https://onco.cc/trials/keynote-775/), [LEAP-002](https://onco.cc/trials/leap-002/), [LEAP-012](https://onco.cc/trials/leap-012/), [Lenvatinib Plus Paclitaxel for Patients With Advanced Biliary Tract Cancer Who Failed to Gemcitabine-based Treatment](https://onco.cc/trials/nct05170438/), [LITESPARK-011](https://onco.cc/trials/nct04586231/), [LITESPARK-012](https://onco.cc/trials/litespark-012/), [Oncolytic Virus H101 Combined With Lenvatinib Plus Toripalimab Compared With FOLFOX in Patients With Advanced Biliary Tract Cancer (OPTIONS-06)](https://onco.cc/trials/nct06919848/), [Pembrolizumab Combination With Lenvatinib in Pts With Recurrent,Persistent,Metastatic or Locally Advanced Vulvar Cancer Not Amenable to Curative Surge](https://onco.cc/trials/nct05903833/), [Pembrolizumab Plus Lenvatinib in Combination With Belzutifan in Solid Tumors (MK-6482-016)](https://onco.cc/trials/nct04976634/), [Pembrolizumab With or Without Lenvatinib or Chemotherapy in First-Line Treatment of Advanced Biliary Tract Cancer](https://onco.cc/trials/nct06230471/), [Phase Ib/II Trial of Envafolimab Plus Lenvatinib for Subjects With Solid Tumors](https://onco.cc/trials/nct05024214/), [Phase II Clinical Study of GemOX Hepatic Arterial Infusion Combined with Lenvatinib and Toripalimab for Advanced and Unresectable Intrahepatic Cholangiocarcinoma and Gallbladder Cancer](https://onco.cc/trials/nct06852287/), [Phase II Study of Iparomlimab and Tuvonralimab (QL1706) in Combination With Albumin-Bound Paclitaxel and Lenvatinib as Second-Line Therapy for Unresectable or Metastatic Biliary Tract Cancer](https://onco.cc/trials/nct07530445/), [Phase II Study of Trastuzumab Rezetecan Combined With Adebrelimab and Lenvatinib as First-Line Therapy for Advanced HER2-Positive/HER2-Low Biliary Tract Cancer](https://onco.cc/trials/nct07670273/), [Phase II Study of Trastuzumab Rezetecan Combined With Adebrelimab and Lenvatinib in Advanced HER2-Positive/Low-Expression Biliary Tract Cancer](https://onco.cc/trials/nct07704177/), [QL1706 Combined With Lenvatinib and GEMOX as First - Line Treatment for Unresectable Biliary Tract Tumors](https://onco.cc/trials/nct06892925/), [QL1706+Lenvatinib+AG Regimen as First-line Treatment for Advanced Metastatic Pancreatic Cancer](https://onco.cc/trials/nct07110064/), [REFLECT](https://onco.cc/trials/reflect/), [Safety and Efficacy Study of Investigational Agents as Monotherapy or in Combination With Pembrolizumab (MK-3475) for the Treatment of Extensive-Stage Small Cell Lung Cancer (ES-SCLC) in Need of Second-Line Therapy (MK-3475-B98/KEYNOTE-B98)](https://onco.cc/trials/nct04938817/), [Study of Envafolimab Alone or With Lenvatinib in Patients With Advanced Endometrial Cancer](https://onco.cc/trials/nct05112991/), [Study of Novel Immunomodulators as Monotherapy and in Combination With Anticancer Agents in Participants With Advanced Hepatobiliary Cancer](https://onco.cc/trials/nct05775159/), [Study of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (MK-3475-365/KEYNOTE-365)](https://onco.cc/trials/nct02861573/), [Study to Evaluate Adverse Events, and Change in Disease Activity, When Intravenously (IV) Infused With Livmoniplimab in Combination With IV Infused Bu](https://onco.cc/trials/nct05822752/), [Substudy 03A: A Study of Immune and Targeted Combination Therapies in Participants With First Line (1L) Renal Cell Carcinoma (MK-3475-03A)](https://onco.cc/trials/nct04626479/), [Substudy 03B: A Study of Immune and Targeted Combination Therapies in Participants With Second Line Plus (2L+) Renal Cell Carcinoma (MK-3475-03B/KEYMAKER-U03)](https://onco.cc/trials/nct04626518/), [The Efficacy and Safety of Lenvatinib Combined With Sindilimab and Nab-paclitaxel in the First-line Treatment for Recurrent and Metastatic Triple Negative Breas](https://onco.cc/trials/nct06140576/), [Trial Exploring Combined Neoadjuvant Therapy With Pembrolizumab/Lenvatinib + Adjuvant Pembrolizumab in Pat. With NSCLC](https://onco.cc/trials/nct04875585/), [Visugromab, Nivolumab and Lenvatinib Compared to Double Placebo and Lenvatinib in Unresectable or Metastatic Hepatocellular Carcinoma Post Anti-PD-(L)](https://onco.cc/trials/nct07219459/)
- pairings: [IMDC risk → first-line regimen choice (RCC)](https://onco.cc/pairings/risk-directed-first-line-rcc/), [Lenvatinib + pembrolizumab (pMMR endometrial cancer after platinum)](https://onco.cc/pairings/lenvatinib-plus-pembrolizumab/)
- ideas: [Use imaging to find the window when tumour blood vessels are working properly](https://onco.cc/ideas/idea-bio2-vascular-normalisation-window/)
- key papers: [Belzutifan plus lenvatinib versus cabozantinib in patients with previously treated advanced renal cell carcinoma (LITESPARK-011): an open-label, randomised, controlled, phase 3 trial](https://onco.cc/key-papers/paper-litespark-011-motzer-lancet-2026/), [KEYNOTE-775: lenvatinib plus pembrolizumab versus chemotherapy for previously treated advanced endometrial cancer](https://onco.cc/key-papers/paper-keynote-775-nejm-2022/), [LEAP-012: transarterial chemoembolisation with lenvatinib plus pembrolizumab versus placebo for unresectable non-metastatic hepatocellular carcinoma](https://onco.cc/key-papers/paper-leap-012-lancet-2025/), [Phase 2 study of lenvatinib in progressive, recurrent or metastatic adenoid cystic carcinoma](https://onco.cc/key-papers/paper-tchekmedyian-lenvatinib-adenoid-cystic-jco-2019/), [REFLECT: lenvatinib versus sorafenib in first-line treatment of unresectable hepatocellular carcinoma](https://onco.cc/key-papers/paper-reflect-lenvatinib-lancet-2018/), [REMORA: lenvatinib in advanced or metastatic thymic carcinoma](https://onco.cc/key-papers/paper-remora-lenvatinib-thymic-carcinoma-lancet-oncol-2020/), [SELECT: lenvatinib versus placebo in radioiodine-refractory differentiated thyroid cancer](https://onco.cc/key-papers/paper-select-lenvatinib-nejm-2015/)

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