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Table of Contents
LETTER TO EDITOR
Year : 2022  |  Volume : 5  |  Issue : 1  |  Page : 177-178

Lenvatinib: With more power comes more toxicity


Onco Cancer Care, Hyderabad, Telangana, India

Date of Submission12-Jan-2022
Date of Decision26-Jan-2022
Date of Acceptance27-Jan-2022
Date of Web Publication31-Mar-2022

Correspondence Address:
Shikhar Kumar
Onco Cancer Care, Hyderabad, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/crst.crst_18_22

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How to cite this article:
Kumar S. Lenvatinib: With more power comes more toxicity. Cancer Res Stat Treat 2022;5:177-8

How to cite this URL:
Kumar S. Lenvatinib: With more power comes more toxicity. Cancer Res Stat Treat [serial online] 2022 [cited 2022 May 21];5:177-8. Available from: https://www.crstonline.com/text.asp?2022/5/1/177/342411



Lenvatinib is an oral multityrosine kinase inhibitor (TKI) that has a wide spectrum of approved indications including thyroid, endometrial, hepatocellular, and renal carcinomas. In the previous issue of CRST, the narrative review of this drug by Goel and Singla[1] must be commended for its comprehensive nature.

Lenvatinib, alone or in combination with immune checkpoint inhibitors (iCPis), has become the standard of care in the first-line systemic therapy of many solid tumors.[2],[3] The CLEAR trial in advanced renal cell carcinoma by Motzer et al. reported a median progression-free survival of 23.9 months and an objective response rate (ORR) of 71%. With the caveat of cross-trial comparisons, these results are superior to those achieved with other first line iCPi plus oral TKI-containing regimens.[4],[5] However, these results came at the cost of significant side effects. A starting dose of 20 mg was chosen for lenvatinib, and 68.8% patients needed a dose reduction, whereas 25% patients discontinued the drug due to unacceptable side effects. The most common significant side effects include diarrhea, palmar − plantar erythrodysesthesia syndrome, hypertension, and weight loss.

A lower starting dose of lenvatinib of 14 mg seems to be more prudent, which can be escalated if the patient tolerates this dose well. In a phase II trial, Pal et al.[6] had reported that there was no significant difference in the ORR between 14 mg and 18 mg doses of lenvatinib, in combination with everolimus for renal cell carcinoma. Indeed, a body weight-based dosing strategy of lenvatinib (<60 kg–8 mg, ≥60 kg–12 mg) based upon pharmacokinetic modeling in hepatocellular carcinomas as done in the REFLECT trial was much better tolerated, with only 37% patients needing a dose reduction and 9% needing a drug withdrawal.[7]

The significance of maintaining the patient's quality-of-life during treatment cannot be over-emphasized.[8] Clinical trial data cannot be directly extrapolated to the real-world setting, especially in a low- and middle-income country like India,[9] where treatment toxicity, both physical and financial, are major hurdles in achieving desirable outcomes.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Goel A, Singla A. Lenvatinib: A narrative drug review. Cancer Res Stat Treat 2021;4:709-20.  Back to cited text no. 1
  [Full text]  
2.
Motzer R, Alekseev B, Rha SY, Porta C, Eto M, Powles T, et al. Lenvatinib plus pembrolizumab or everolimus for advanced renal cell carcinoma. N Engl J Med 2021;384:1289-300.  Back to cited text no. 2
    
3.
Makker V, Taylor MH, Aghajanian C, Oaknin A, Mier J, Cohn AL, et al. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer. J Clin Oncol 2020;38:2981-92.  Back to cited text no. 3
    
4.
Rini BI, Plimack ER, Stus V, Gafanov R, Hawkins R, Nosov D, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 2019;380:1116-27.  Back to cited text no. 4
    
5.
Kapoor A. Current systemic therapy options in advanced clear cell renal cell cancer. Cancer Res Stat Treat 2021;4:124-6.  Back to cited text no. 5
  [Full text]  
6.
Pal SK, Puente J, Heng DY, Glen H, Koralewski P, Stroyakovskiy D, et al. Phase II trial of lenvatinib (LEN) at two starting doses+everolimus (EVE) in patients (pts) with renal cell carcinoma (RCC): Results by independent imaging review (IIR) and prior immune checkpoint inhibition (ICI). J Clin Oncol 2021;39:307.  Back to cited text no. 6
    
7.
Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: A randomised phase 3 non-inferiority trial. Lancet 2018;391:1163-73.  Back to cited text no. 7
    
8.
Salins N. Health-related quality of life: Is it a missing feature in the Indian cancer setting? Cancer Res Stat Treat 2019;2:213-4.  Back to cited text no. 8
  [Full text]  
9.
Noronha V. Making a case for cancer research in India. Cancer Res Stat Treat 2018;1:71-4.  Back to cited text no. 9
  [Full text]  




 

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