Impressive and Prolonged Response with Lenvatinib in a Highly Pretreated Patient with Metastatic Clear Cell Renal Cancer: A Case Report
Main Article Content
Keywords
case report, lenvatinib, renal cell carcinoma, tyrosine kinase inhibitor, VHL mutation
Abstract
Clear cell renal carcinoma (ccRCC) can occur in young people and could be associated with an aggressive behavior. While for the first-line treatment in metastatic disease, there is an agreement to rely on an immunotherapy (IO)-based combination regimen, no standard second-line regimens exist. Generally, tyrosine kinase inhibitors (TKIs) are employed, even in sequence, although no trials have demonstrated yet the best succession. Herein, we present the case of a 39-year-old male, with a very aggressive ccRCC with somatic VHL mutation and distant metastases at diagnosis. He was treated with four different lines of therapies, including TKIs, with progressive multiple tumor deposits. Lenvatinib alone as the fifth line was able to induce a remarkable and prolonged tumor shrinkage with manageable toxicities.
References
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19. Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: A randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015;16(15):1473–82. 10.1016/S1470-2045(15)00290-9
20. Wiele AJ, Bathala TK, Hahn AW, Xiao L, Duran M, Ross JA, et al. Lenvatinib with or without everolimus in patients with metastatic renal cell carcinoma after immune checkpoint inhibitors and vascular endothelial growth factor receptor–Tyrosine kinase inhibitor therapies. Oncologist. 2021;26(6):476–82. 10.1002/onco.13770
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23. Choueiri TK, Vaziri SAJ, Jaeger E, Elson P, Wood L, Bhalla IP, et al. von Hippel-Lindau gene status and response to vascular endothelial growth factor targeted therapy for metastatic clear cell renal cell carcinoma. J Urol. 2008;180(3):860–6. 10.1016/j.juro.2008.05.015
24. Motzer RJ, Hutson TE, Hudes GR, Figlin RA, Martini J, English PA, et al. Investigation of novel circulating proteins, germ line single-nucleotide polymorphisms, and molecular tumor markers as potential efficacy biomarkers of first-line sunitinib therapy for advanced renal cell carcinoma. Cancer Chemother Pharmacol. 2014;74(4):739–50. 10.1007/s00280-014-2539-0
25. Cowey CL, Rathmell WK. VHL Gene mutations in renal cell carcinoma: Role as a biomarker of disease outcome and drug efficacy. Curr Oncol Rep. 2009;11(2):94–101. 10.1007/s11912-009-0015-5
26. Ikuta K, Yano S, Wang W, Yamada T, Ogino H, Kakiuchi S, et al. E7080, a multi–tyrosine kinase inhibitor, suppresses the progression of malignant pleural mesothelioma with different proangiogenic cytokine production profiles. Clin Cancer Res. 2009;15(23):7229–37. 10.1158/1078-0432.CCR-09-1980
27. Hussein Z, Mizuo H, Hayato S, Namiki M, Shumaker R. Clinical pharmacokinetic and pharmacodynamic profile of lenvatinib, an orally active, small-molecule, multitargeted tyrosine kinase inhibitor. Eur J Drug Metab Pharmacokinet. 2017;42(6):903–14. 10.1007/s13318-017-0403-4
28. Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, et al. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011;10(12):2298–308. 10.1158/1535-7163.MCT-11-0264
29. Motzer DRJ. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: Overall survival analysis and updated results from a randomised phase 3 trial. Lancet. 2013;14(6):552–62. 10.1016/S1470-2045(13)70093-7
2. Hsieh JJ, Purdue MP, Signoretti S, Swanton C, Albiges L, Schmidinger M, et al. Renal cell carcinoma. Nat Rev Dis Primer. 2017;3:17009.
3. Tate JG, Bamford S, Jubb HC, Sondka Z, Beare DM, Bindal N, et al. COSMIC: The catalogue of somatic mutations in cancer. Nucleic Acids Res. 2019;47(D1):D941–7. 10.1093/nar/gky1015
4. Sankin A, Hakimi AA, Mikkilineni N, Ostrovnaya I, Silk MT, Liang Y, et al. The impact of genetic heterogeneity on biomarker development in kidney cancer assessed by multiregional sampling. Cancer Med. 2014;3(6):1485–92. 10.1002/cam4.293
5. Heng DYC, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C, et al. Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor–targeted agents: Results from a large, multicenter study. J Clin Oncol. 2009;27(34):5794–9. 10.1200/JCO.2008.21.4809
6. Heng DYC, Xie W, Regan MM, Harshman LC, Bjarnason GA, Vaishampayan UN, et al. External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: A population-based study. Lancet Oncol. 2013;14(2):141–8. 10.1016/S1470-2045(12)70559-4
7. Tran J, Ornstein MC. Clinical review on the management of metastatic renal cell carcinoma. JCO Oncol Pract. 2022;18(3):187–96. 10.1200/OP.21.00419
8. SEER Cancer Stat facts: Kidney and renal pelvis cancer [Internet]. Available from: https://seer.cancer.gov/statfacts/html/kidrp.html
9. Medical Research Council Renal Cancer Collaborators. Interferon-α and survival in metastatic renal carcinoma: Early results of a randomised controlled trial. Lancet. 1999;353(9146):14–17.
10. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27(22):3584–90. 10.1200/JCO.22.02623
11. Rini BI, Plimack ER, Stus V, Waddell T, Gafanov R, Pouliot F, et al. Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma (ccRCC): Results from 42-month follow-up of KEYNOTE-426. J Clin Oncol. 2021;39(15_suppl):4500.
12. Motzer RJ, McDermott DF, Escudier B, Burotto M, Choueiri TK, Hammers HJ, et al. Conditional survival and long-term efficacy with nivolumab plus ipilimumab versus sunitinib in patients with advanced renal cell carcinoma. Cancer. 2022;128(11):2085–97. 10.1002/cncr.34180
13. Burotto M, Powles T, Escudier B, Apolo AB, Bourlon MT, Shah AY, et al. Nivolumab plus cabozantinib vs sunitinib for first-line treatment of advanced renal cell carcinoma (aRCC): 3-year follow-up from the phase 3 CheckMate 9ER trial. J Clin Oncol. 2023;41(no. 6_suppl):603.
14. Motzer RJ, Porta C, Eto M, Powles T, Grünwald V, Hutson TE, et al. Final prespecified overall survival (OS) analysis of CLEAR: 4-year follow-up of lenvatinib plus pembrolizumab (L+P) vs sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC). J Clin Oncol. 2023;41(16_suppl):4502.
15. Choueiri TK, Escudier B, Powles T, Tannir NM, Mainwaring PN, Rini BI, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): Final results from a randomised, open-label, phase 3 trial. Lancet Oncol. 2016;17(7):917–27. 10.1016/S1470-2045(16)30107-3
16. Procopio G, Claps M, Pircher C, Porcu L, Sepe P, Guadalupi V, et al. A multicenter phase 2 single arm study of cabozantinib in patients with advanced or unresectable renal cell carcinoma pre-treated with one immune-checkpoint inhibitor: The BREAKPOINT trial (Meet-Uro trial 03). Tumori. 2023;109(1):129–37. 10.1177/03008916221138881
17. Wells JC, Dudani S, Gan CL, Stukalin I, Azad AA, Liow E, et al. Clinical effectiveness of second-line sunitinib following immuno-oncology therapy in patients with metastatic renal cell carcinoma: A real-world study. Clin Genitourin Cancer. 2021;19(4):354–61. 10.1016/j.clgc.2021.03.006
18. Rini BI, Pal SK, Escudier BJ, Atkins MB, Hutson TE, Porta C, et al. Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): A phase 3, multicentre, randomised, controlled, open-label study. Lancet Oncol. 2020;21(1):95–104. 10.1016/S1470-2045(19)30735-1
19. Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, et al. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: A randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015;16(15):1473–82. 10.1016/S1470-2045(15)00290-9
20. Wiele AJ, Bathala TK, Hahn AW, Xiao L, Duran M, Ross JA, et al. Lenvatinib with or without everolimus in patients with metastatic renal cell carcinoma after immune checkpoint inhibitors and vascular endothelial growth factor receptor–Tyrosine kinase inhibitor therapies. Oncologist. 2021;26(6):476–82. 10.1002/onco.13770
21. Kaelin WG. The von Hippel–Lindau tumour suppressor protein: O2 sensing and cancer. Nat Rev Cancer. 2008;8(11):865–73. 10.1038/nrc2502
22. Rini BI, Jaeger E, Weinberg V, Sein N, Chew K, Fong K, et al. Clinical response to therapy targeted at vascular endothelial growth factor in metastatic renal cell carcinoma: Impact of patient characteristics and Von Hippel-Lindau gene status. BJU Int. 2006;98(4):756–62. 10.1111/j.1464-410X.2006.06376.x
23. Choueiri TK, Vaziri SAJ, Jaeger E, Elson P, Wood L, Bhalla IP, et al. von Hippel-Lindau gene status and response to vascular endothelial growth factor targeted therapy for metastatic clear cell renal cell carcinoma. J Urol. 2008;180(3):860–6. 10.1016/j.juro.2008.05.015
24. Motzer RJ, Hutson TE, Hudes GR, Figlin RA, Martini J, English PA, et al. Investigation of novel circulating proteins, germ line single-nucleotide polymorphisms, and molecular tumor markers as potential efficacy biomarkers of first-line sunitinib therapy for advanced renal cell carcinoma. Cancer Chemother Pharmacol. 2014;74(4):739–50. 10.1007/s00280-014-2539-0
25. Cowey CL, Rathmell WK. VHL Gene mutations in renal cell carcinoma: Role as a biomarker of disease outcome and drug efficacy. Curr Oncol Rep. 2009;11(2):94–101. 10.1007/s11912-009-0015-5
26. Ikuta K, Yano S, Wang W, Yamada T, Ogino H, Kakiuchi S, et al. E7080, a multi–tyrosine kinase inhibitor, suppresses the progression of malignant pleural mesothelioma with different proangiogenic cytokine production profiles. Clin Cancer Res. 2009;15(23):7229–37. 10.1158/1078-0432.CCR-09-1980
27. Hussein Z, Mizuo H, Hayato S, Namiki M, Shumaker R. Clinical pharmacokinetic and pharmacodynamic profile of lenvatinib, an orally active, small-molecule, multitargeted tyrosine kinase inhibitor. Eur J Drug Metab Pharmacokinet. 2017;42(6):903–14. 10.1007/s13318-017-0403-4
28. Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, et al. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Mol Cancer Ther. 2011;10(12):2298–308. 10.1158/1535-7163.MCT-11-0264
29. Motzer DRJ. Axitinib versus sorafenib as second-line treatment for advanced renal cell carcinoma: Overall survival analysis and updated results from a randomised phase 3 trial. Lancet. 2013;14(6):552–62. 10.1016/S1470-2045(13)70093-7
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Apr 10, 2024
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Impressive and Prolonged Response with Lenvatinib in a Highly Pretreated Patient with Metastatic Clear Cell Renal Cancer: A Case Report. (2024). Journal of Kidney Cancer and VHL, 11(2), 1-6. https://doi.org/10.15586/jkcvhl.v11i2.317
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Kidney Cancer: Case Reports
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