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| LETTER TO EDITOR |
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| Year : 2022 | Volume
: 5
| Issue : 1 | Page : 177-178 |
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Lenvatinib: With more power comes more toxicity
Shikhar Kumar
Onco Cancer Care, Hyderabad, Telangana, India
| Date of Submission | 12-Jan-2022 |
| Date of Decision | 26-Jan-2022 |
| Date of Acceptance | 27-Jan-2022 |
| Date of Web Publication | 31-Mar-2022 |
Correspondence Address:
Shikhar Kumar
Onco Cancer Care, Hyderabad, Telangana
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/crst.crst_18_22
How to cite this article:
Kumar S. Lenvatinib: With more power comes more toxicity. Cancer Res Stat Treat 2022;5:177-8 |
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 | |  |
| 1. | Goel A, Singla A. Lenvatinib: A narrative drug review. Cancer Res Stat Treat 2021;4:709-20.  [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. |
| 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. |
| 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. |
| 5. | Kapoor A. Current systemic therapy options in advanced clear cell renal cell cancer. Cancer Res Stat Treat 2021;4:124-6. [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. |
| 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. |
| 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. [Full text] |
| 9. | Noronha V. Making a case for cancer research in India. Cancer Res Stat Treat 2018;1:71-4. [Full text] |
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