Lenvatinib (Lenvima)

General information

Class/mechanism: Tyrosine kinase inhibitor of multiple receptor tyrosine kinases (RTKs), including: vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4); fibroblast growth factor (FGF) receptors FGFR1, FGFR2, FGFR3, and FGFR4; platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET. Inhibition of these receptor tyrosine kinases interferes with cancer cells' proliferation and pathogenic angiogenesis.
Route: PO
Extravasation: n/a

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the package insert.

Diseases for which it is established

• Endometrial cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Differentiated thyroid cancer

Diseases for which it is used

• Cholangiocarcinoma

Patient drug information

• Lenvatinib (Lenvima) package insert
• Lenvatinib (Lenvima) patient drug information (Chemocare)
• Lenvatinib (Lenvima) patient drug information (UpToDate)

History of changes in FDA indication

Differentiated thyroid cancer

• 2015-02-13: Approved for the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer. (Initial approval; based on SELECT)

Endometrial cancer

• 2019-09-17: Accelerated approval in combination with Pembrolizumab (Keytruda) for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) and who have disease progression following prior systemic therapy but are not candidates for curative surgery or radiation. (Based on KEYNOTE-146)
  • 2021-07-21: Converted to regular approval in combination with Pembrolizumab (Keytruda) for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) and who have disease progression following prior systemic therapy but are not candidates for curative surgery or radiation. (Based on KEYNOTE-775)

Hepatocellular carcinoma

• 2018-08-16: Approved for first-line treatment of patients with unresectable hepatocellular carcinoma (HCC). (Based on REFLECT)

Renal cell carcinoma

• 2016-05-13: Approved in combination with everolimus, for the treatment of advanced renal cell carcinoma following one prior anti-angiogenic therapy. (Based on E7080-G000-205)
• 2021-08-10: Approved in combination with Pembrolizumab (Keytruda) for first-line treatment of adult patients with advanced renal cell carcinoma (RCC). (Based on CLEAR)

History of changes in EMA indication

Differentiated thyroid cancer

• 2015-05-28: Initial authorization as Lenvima. Lenvima is indicated as monotherapy for the treatment of adult patients with progressive, locally advanced or metastatic, differentiated (papillary/follicular/Hürthle cell) thyroid carcinoma (DTC), refractory to radioactive iodine (RAI).

Endometrial cancer

• 2021-11-26: Extension of indication to include lenvatinib in combination with pembrolizumab for the treatment of adult patients with advanced endometrial carcinoma (EC) who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

Hepatocellular carcinoma

• 2018-08-20: Lenvima is indicated as monotherapy for the treatment of adult patients with advanced or unresectable hepatocellular carcinoma (HCC) who have received no prior systemic therapy.

Renal cell carcinoma

• 2016-08-25: Initial authorization as Kisplyx. Kisplyx is indicated in combination with everolimus for the treatment of adult patients with advanced renal cell carcinoma (RCC) following one prior vascular endothelial growth factor (VEGF)-targeted therapy. (Based on E7080-G000-205)
• 2021-11-26: Extension of indication to include Kisplyx in combination with pembrolizumab first line treatment of adults with advanced renal cell carcinoma (RCC).

History of changes in Health Canada indication

• 2019-09-20: Notice of compliance with conditions in combination with pembrolizumab, for the treatment of adult patients with advanced endometrial carcinoma that is not microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior platinum-based systemic therapy, and are not candidates for curative surgery or radiation.

History of changes in PMDA indication

Endometrial cancer

• 2021-12-24: New indication and a new dosage for the treatment of unresectable advanced or recurrent endometrial carcinoma that has progressed after cancer chemotherapy.

Hepatocellular carcinoma

• 2018-03-23: New additional indication and a new dosage indicated for the treatment of unresectable hepatic cell carcinoma.

Renal cell carcinoma

• 2022-02-25: New indication and a new dosage for the treatment of unresectable or metastatic renal cell carcinoma.

Thymic carcinoma

• 2021-03-21: New indication for the treatment of unresectable thymic carcinoma.

Thyroid cancer

• 2015-03-26: Initial approval for the treatment of unresectable thyroid cancer.

Also known as

• Code name: E-7080
• Brand name: Kisplyx, Lenvima