Lenvatinib
- Generic Name
- Lenvatinib
- Brand Names
- Lenvima 10, Kisplyx, Lenvima
- Drug Type
- Small Molecule
- Chemical Formula
- C21H19ClN4O4
- CAS Number
- 417716-92-8
- Unique Ingredient Identifier
- EE083865G2
- Background
Lenvatinib is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvatinib also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. These receptor tyrosine kinases (RTKs) located in the cell membrane play a central role in the activation of signal transduction pathways involved in the normal regulation of cellular processes, such as cell proliferation, migration, apoptosis and differentiation, and in pathogenic angiogenesis, lymphogenesis, tumour growth and cancer progression. In particular, VEGF has been identified as a crucial regulator of both physiologic and pathologic angiogenesis and increased expression of VEGF is associated with a poor prognosis in many types of cancers.
Lenvatinib is indicated for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine (RAI)-refractory differentiated thyroid cancer. Most patients with thyroid cancer have a very good prognosis with treatment (98% 5 year survival rate) involving surgery and hormone therapy. However, for patients with RAI-refractory thyroid cancer, treatment options are limited and the prognosis is poor, leading to a push for the development of more targeted therapies such as lenvatinib.
- Indication
Lenvatinib is indicated for the treatment of the following cancerous conditions:
Differentiated Thyroid Cancer (DTC)
Renal Cell Carcinoma (RCC)
Hepatocellular Carcinoma (HCC)
Endometrial Carcinoma
- Associated Conditions
- Advanced Renal Cell Carcinoma, Endometrial Carcinoma, Unresectable Hepatocellular Carcinoma (HCC), Progressive, locally advanced radioactive iodine-refractory Differentiated Thyroid Cancer (DTC), Progressive, metastatic radioactive iodine-refractory Differentiated Thyroid Cancer (DTC)
FDA Approves BMS's Opdivo/Yervoy Combination for First-Line Treatment of Advanced Liver Cancer
• Bristol-Myers Squibb's Opdivo (nivolumab) and Yervoy (ipilimumab) combination has received FDA approval for first-line treatment of unresectable or metastatic hepatocellular carcinoma, demonstrating a 21% reduced risk of death compared to standard therapies.
• The CheckMate-9DW trial showed significant survival benefits with a median overall survival of 23.7 months for the immunotherapy combination versus 20.6 months for tyrosine kinase inhibitors, potentially establishing a new standard of care.
• This approval marks a significant advancement for HCC patients, addressing an unmet need in a disease whose incidence has tripled over four decades, though treatment decisions may be influenced by the combination's known toxicity profile.
Tecentriq and Avastin Combination Now Funded for Advanced Liver Cancer in New Zealand
• Pharmac has approved public funding for Tecentriq (atezolizumab) in combination with bevacizumab for hepatocellular carcinoma (HCC) in New Zealand, benefiting approximately 70 patients diagnosed annually.
• The immunotherapy combination has demonstrated a 34% reduction in risk of death, with half of patients surviving beyond 18 months, representing a significant improvement over previous treatment options.
• Māori and Pacific populations are disproportionately affected by HCC due to higher prevalence of risk factors including Hepatitis B and C, with Māori patients 31% more likely to die from liver cancer than non-Māori.
Immunotherapy in Gastric Cancer: Moving to Earlier Disease Stages and Optimizing Combination Approaches
• Leading oncologist Dr. Yelena Janjigian emphasizes the need to advance immunotherapy to earlier disease stages in gastric, GEJ, and esophageal cancers, with promising data expected from the MATTERHORN study.
• Recent evidence from phase 3 trials TOPGEAR and ESOPEC demonstrates that radiation therapy does not improve survival outcomes in gastric/GEJ cancers, challenging conventional treatment approaches.
• FLOT chemotherapy regimen combined with durvalumab represents an optimal treatment strategy for the perioperative setting, addressing the systemic nature of gastric cancer rather than focusing on localized radiation therapy.
Zimberelimab Plus Lenvatinib Shows Promise in Advanced Cervical Cancer After ICI Failure
• Phase 2 trial results demonstrate that zimberelimab combined with lenvatinib achieved a 33.3% objective response rate in patients with advanced cervical cancer who progressed after prior immune checkpoint inhibitor therapy.
• The combination therapy demonstrated remarkable disease control, with 96.7% of patients experiencing stable disease or better, and a median progression-free survival of 7.1 months.
• Treatment was well-tolerated with mostly mild to moderate adverse effects, with only 10% of patients experiencing grade 3/4 treatment-related adverse events.
Cadonilimab Plus Lenvatinib Shows Promise in Advanced Endometrial Cancer After Platinum Failure
• A phase 2 trial demonstrated that the combination of cadonilimab and lenvatinib achieved a 42.9% objective response rate in patients with advanced endometrial cancer who progressed after platinum-based chemotherapy.
• The novel regimen combining the PD-1/CTLA-4 bispecific antibody cadonilimab with the tyrosine kinase inhibitor lenvatinib showed a disease control rate of 92.9% with manageable toxicity profile.
• The treatment showed activity across molecular subtypes, with particularly encouraging results in patients with no specific molecular profile, potentially offering a new therapeutic option for this difficult-to-treat population.
Pharmaceutical Industry Braces for $236 Billion Patent Cliff by 2030: Strategic Responses from Major Players
• The global pharmaceutical industry faces a $236 billion patent cliff between 2025-2030, with nearly 70 blockbuster drugs losing exclusivity and exposing major companies to significant revenue losses.
• Key drugs approaching patent expiration include Merck's Keytruda ($25B), Bristol-Myers Squibb's Eliquis ($12B), and Johnson & Johnson's Stelara ($10.9B), forcing companies to rapidly adapt through pipeline diversification and cost-cutting measures.
• Companies are responding with increased M&A activity, AI-driven R&D efficiency, and strategic pivots to high-growth therapeutic areas, while the cliff will likely improve drug affordability but potentially slow innovation.
CLEAR Trial Update: Lenvatinib-Pembrolizumab Combination Shows Sustained Efficacy in Advanced Renal Cell Carcinoma
• New analyses from the phase 3 CLEAR trial demonstrate sustained long-term benefits of lenvatinib plus pembrolizumab combination therapy in advanced renal cell carcinoma patients.
• The study examined the relationship between tumor burden at progression and IMDC risk classification changes, providing valuable insights into disease evolution during treatment.
• Lead investigator Dr. Thomas Hutson confirms the combination therapy's position as one of the most active treatment regimens for advanced RCC, reinforcing its role in clinical practice.
Phase 3 Trial Shows Promising Results for Novel Encapsulated Cell Therapy in MacTel Treatment
• Phase 3 clinical trials of NT-501, an encapsulated cell therapy delivering CNTF, demonstrated significant reduction in disease progression for macular telangiectasia type 2 patients, with up to 52% reduction in ellipsoid zone loss.
• The innovative implantable device, developed by Neurotech, maintains long-term viability with CNTF production documented for up to 14.5 years, offering a potential alternative to frequent intravitreal injections.
• FDA review of the therapy is currently underway with a PDUFA date set for March 18, 2025, marking a potential breakthrough in MacTel treatment.
Akeso Completes Patient Enrollment in Phase III Trial Comparing Ivonescimab for First-Line Squamous NSCLC Treatment
• Akeso has completed enrollment for the HARMONi-6 Phase III trial comparing ivonescimab plus chemotherapy to tislelizumab plus chemotherapy for first-line squamous non-small cell lung cancer treatment.
• Ivonescimab, a novel PD-1/VEGF bispecific antibody, is currently being evaluated in six Phase III lung cancer trials globally, with potential applications across multiple cancer types.
• The drug addresses a significant unmet need among 520,000 annual cases of advanced sq-NSCLC patients, offering a promising alternative for those ineligible for current anti-angiogenesis treatments.
TiNivo-2 Trial Shows No Added Benefit of Nivolumab Combination in IO-Refractory RCC Treatment
• Phase 3 TiNivo-2 trial demonstrates tivozanib monotherapy matches the efficacy of tivozanib-nivolumab combination in IO-refractory renal cell carcinoma, with both arms showing 19% objective response rates.
• Study reveals patients receiving tivozanib monotherapy after ICI therapy achieved a median PFS of 9.2 months, while those in third-line setting reached 3.7 months regardless of treatment arm.
• Trial uniquely allowed patients with prior TKI intervention, with approximately 30% of participants having received intervening TKI therapy before enrollment.
Nivolumab Plus Ipilimumab Shows Promise in Advanced Hepatocellular Carcinoma
• The combination of nivolumab and ipilimumab has shown significantly improved overall survival in patients with unresectable hepatocellular carcinoma (HCC).
• The CheckMate 9DW trial demonstrated a median overall survival of 23.7 months with nivolumab/ipilimumab compared to 20.6 months with lenvatinib or sorafenib.
• The combination therapy also resulted in a higher objective response rate of 36% versus 13% with lenvatinib/sorafenib, indicating better tumor control.
• The FDA has accepted the application for nivolumab plus ipilimumab as a first-line treatment for unresectable HCC, with a decision expected by April 2025.
Merck and Eisai's Keytruda-Lenvima Combo Shows Mixed Phase 3 Results in Gastric Cancer
A Phase 3 trial evaluating Merck and Eisai's combination of Keytruda (pembrolizumab) and Lenvima (lenvatinib) demonstrated improved progression-free survival but failed to show overall survival benefit in HER2-negative gastroesophageal adenocarcinoma. The LEAP-015 study results highlight the complex nature of treating advanced gastric cancer while maintaining the drugs' existing approved indications.
European Commission Approves GSK's Jemperli Plus Chemotherapy for Advanced Endometrial Cancer
• The European Commission has approved Jemperli (dostarlimab) in combination with chemotherapy for first-line treatment of advanced or recurrent endometrial cancer.
• The approval expands the indication to include patients with mismatch repair proficient/microsatellite stable (MMRp/MSS) tumors, representing approximately 75% of cases.
• The RUBY trial demonstrated a 31% reduction in the risk of death with Jemperli plus chemotherapy compared to chemotherapy alone, with a median OS of 44.6 months.
• Jemperli, a PD-1 blocking antibody, is now an approved immuno-oncology-based treatment option for all patients with advanced endometrial cancer in the EU.
TACE Plus Camrelizumab and Rivoceranib Improves PFS in Unresectable HCC
• The CARES-005 study demonstrated that adding camrelizumab and rivoceranib to TACE significantly prolonged progression-free survival (PFS) in patients with unresectable hepatocellular carcinoma (HCC).
• Median PFS was 10.8 months with TACE plus camrelizumab and rivoceranib, compared to 3.2 months with TACE alone (HR 0.34, P<0.0001) at a median follow-up of 13.6 months.
• Objective response and disease control rates were also higher in the TACE-CR group, indicating enhanced antitumor efficacy with the combination therapy.
• The safety profile of the combination was manageable, with adverse events consistent with those known for TACE, camrelizumab, and rivoceranib.
KEYNOTE-B61 Demonstrates Robust Data for Non-Clear Cell Renal Cell Carcinoma Treatment
• The KEYNOTE-B61 trial, investigating pembrolizumab plus lenvatinib, shows more robust data than the CA-209 9KU trial for non-clear cell renal cell carcinoma (non-ccRCC).
• KEYNOTE-B61 enrolled 158 patients with various non-ccRCC subtypes, reporting a median PFS of 18 months, providing more reliable findings due to its larger sample size.
• While nivolumab plus cabozantinib remains a viable option, KEYNOTE-B61's pembrolizumab plus lenvatinib has emerged as a preferred treatment for many oncologists treating non-ccRCC.
• Cross-trial comparisons are unreliable due to differences in baseline patient populations, but KEYNOTE-B61 offers narrow confidence intervals and broader representation of histologic subtypes.
IO/TKI Doublets Show Consistent Efficacy in Metastatic Clear Cell Renal Cell Carcinoma
• Phase 3 trials KEYNOTE-426, CheckMate-9ER, and CLEAR reinforce the efficacy of first-line immuno-oncology (IO)/TKI doublets in metastatic clear cell renal cell carcinoma (ccRCC).
• Progression-free survival (PFS) consistently improved across International mRCC Database Consortium risk groups with IO/TKI regimens compared to sunitinib.
• Overall survival (OS) benefit was mainly observed in intermediate- and poor-risk patient populations, with less clear benefit in favorable-risk groups.
• Managing adverse effects through early interruption and dose reduction of the TKI component is crucial for maintaining patients on these treatments.
BMS's Opdivo/Yervoy Combo Shows Survival Benefit in First-line Liver Cancer Treatment
Bristol-Myers Squibb's immunotherapy combination of Opdivo and Yervoy has demonstrated superior survival benefits in first-line hepatocellular carcinoma treatment, with FDA decision expected by April 2024. The therapy showed a 36% objective response rate compared to 13% for standard treatments, potentially offering a new option for patients with unresectable liver cancer.
First-Line Lenvima Plus Keytruda Misses Mark in Endometrial Cancer
A phase 3 trial found that first-line treatment with Lenvima (lenvatinib) plus Keytruda (pembrolizumab) did not significantly improve survival and progression in patients with advanced or recurrent endometrial cancer compared to chemotherapy, according to findings published in the Journal of Clinical Oncology.
Global Diabetic Retinopathy Clinical Trials Landscape Analysis Reveals Key Research Trends for 2024
• A comprehensive analysis of global diabetic retinopathy clinical trials has been released, offering insights into trial distribution across G7 and E7 countries and various research phases.
• The report highlights significant trends in trial enrollment patterns over the past five years, providing valuable data for healthcare stakeholders and pharmaceutical companies.
• The analysis covers detailed assessment of trial statuses, sponsor types, and endpoint evaluations, helping identify key opportunities and challenges in diabetic retinopathy research.
AstraZeneca and Merck Drugs Show Promise in Liver Cancer Treatment
• Late-stage studies published in The Lancet reveal that AstraZeneca's Imfinzi and Merck's Keytruda, when combined with other treatments, significantly delayed liver cancer progression.
• Patients with surgically untreatable tumors experienced several months of extended progression-free survival with these checkpoint inhibitors.
• The Keytruda study demonstrated an average of 14.6 months without cancer progression compared to 10 months in the control group using Keytruda, Lenvima, and chemoembolisation.
• Another study showed that Imfinzi combined with Avastin and chemoembolisation resulted in 15 months before cancer progression, versus 10 months for Imfinzi alone.
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