|LETTER TO EDITOR
|Year : 2022 | Volume
| Issue : 1 | Page : 178-179
Lenvatinib: A potent oral tyrosine kinase inhibitor across multiple histologies with differing dosages
Bipinesh Sansar1, Neha Singh2, Arpita Singh1
1 Department of Medical Oncology, MPMMCC and HBCH, Varanasi, Uttar Pradesh, India
2 Department of Pathology, MPMMCC and HBCH, Varanasi, Uttar Pradesh, India
|Date of Submission||17-Jan-2022|
|Date of Decision||28-Jan-2022|
|Date of Acceptance||01-Feb-2022|
|Date of Web Publication||31-Mar-2022|
Department of Medical Oncology, MPMMCC and HBCH, Varanasi, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Sansar B, Singh N, Singh A. Lenvatinib: A potent oral tyrosine kinase inhibitor across multiple histologies with differing dosages. Cancer Res Stat Treat 2022;5:178-9
|How to cite this URL:|
Sansar B, Singh N, Singh A. Lenvatinib: A potent oral tyrosine kinase inhibitor across multiple histologies with differing dosages. Cancer Res Stat Treat [serial online] 2022 [cited 2022 May 21];5:178-9. Available from: https://www.crstonline.com/text.asp?2022/5/1/178/342412
We read with interest the drug review on lenvatinib published in the previous issue of the journal. Goel and Singla have extensively discussed the various indications and nuances associated with the use of this drug.
We noted the differential recommended drug dosing for different indications, particularly in advanced hepatocellular carcinoma. The first approved indication for lenvatinib in thyroid cancer was at a starting dose of 24 mg once daily. However, in advanced hepatocellular carcinoma, the recommended starting doses are 12 mg or 8 mg, based on whether the patient's weight is above or below 60 kg, respectively; this is essentially half the earlier recommended dose, and is also substantially lower than that recommended in renal cell carcinoma and endometrial carcinoma.
This is because in the early phase trials of lenvatinib in advanced hepatocellular carcinoma, a significantly higher proportion of patients developed dose-limiting toxicities. Subsequently, pharmacokinetic modeling showed a correlation between body weight, liver function as measured by the Child–Pugh score, and increased toxicity. For cabozantinib as well, the doses recommended for thyroid cancer (140 mg once daily) and for renal and hepatocellular cancers (60 mg once daily) are lower. Thus, in cancers that originate from or involve the organs of metabolism, the pharmacokinetics and pharmacodynamics of these drugs are altered resulting in reduced tolerance to these drugs.
It is essential to maintain a fine balance between the tolerability and efficacy of oral multi-targeted tyrosine kinase inhibitors. Pharmacokinetics-based dose modification is being explored as a method to attain this for various tyrosine kinase inhibitors.
Additionally, biomarker-based selection of patients is another mechanism to refine the patient selection for choosing between different drugs as options in later lines of therapy., Angiopoietin-2 and fibroblast growth factor-23 have emerged as particularly promising biomarkers for lenvatinib and could help guide the selection of therapy.
Lenvatinib increases the levels of programmed death-ligand 1 and facilitates tumor-associated macrophages M1 type, thereby enhancing anti-tumor immune responses. Therefore, the combination of this drug with immunotherapy appears exciting and multiple trials are being conducted to evaluate this.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Goel A, Singla A. Lenvatinib: A narrative drug review. Cancer Res Stat Treat 2021;4:709-20. [Full text]
Tamai T, Hayato S, Hojo S, Suzuki T, Okusaka T, Ikeda K, et al.
Dose finding of lenvatinib in subjects with advanced hepatocellular carcinoma based on population pharmacokinetic and exposure-response analyses. J Clin Pharmacol 2017;57:1138-47.
Nguyen L, Holland J, Ramies D, Mamelok R, Benrimoh N, Ciric S, et al.
Effect of renal and hepatic impairment on the pharmacokinetics of cabozantinib. J Clin Pharmacol 2016;56:1130-40.
Lucas CJ, Martin JH. Pharmacokinetic-guided dosing of new oral cancer agents. J Clin Pharmacol 2017;57 Suppl 10:S78-98.
Finn RS, Kudo M, Cheng AL, Wyrwicz L, Ngan RK, Blanc JF, et al.
Pharmacodynamic biomarkers predictive of survival benefit with lenvatinib in unresectable hepatocellular carcinoma: from the phase III REFLECT study. Clin Cancer Res 2021;27:4848-58.
Khaddar S, Mishra BK. Biomarkers for response to immune checkpoint inhibitors: Where do we stand? Cancer Res Stat Treat 2021;4:363-4. [Full text]
Capozzi M, De Divitiis C, Ottaiano A, von Arx C, Scala S, Tatangelo F, et al.
Lenvatinib, a molecule with versatile application: from preclinical evidence to future development in anti-cancer treatment. Cancer Manag Res 2019;11:3847-60.