Preview

Cancer Urology

Advanced search

Efficacy and safety of lenvatinib in combination with everolimus in metastatic renal cell carcinoma resistant to antiangiogenic targeted therapy: Russian multicenter observational study ROSLERCM

https://doi.org/10.17650/1726-9776-2019-15-3-56-69

Abstract

Objective: an assessment of efficacy and safety of lenvatinib in combination with everolimus in unselected patients with metastatic renal cell carcinoma (mRCC) progressed during or following ≥1 line of antiangiogenic targeted therapy.

Material. Russian multicenter observational study ROSLERCM included 73 consecutive patients with morphologically verified mRCC progressed during or following ≥1 line of antiangiogenic targeted therapy, treated with lenvatinib (18 mg/d) and everolimus (5 mg/d) in 20 Russian centers. Median age of the patients was 59 (23–73) years, a male-to-female ratio – 3:1. Most common histological type of kidney cancer was clear-cell RCC (71 (95.8 %)). More than 2 lines of previous therapy were administered in 45 (61.6 %) cases. Most patients were diagnosed with multiple metastases (71 (97.3 %)) in >1 site (61 (83.6 %)). Nephrectomy was performed in 87.7 % (64/73) of cases. At the combined therapy start ECOG PS 2–4 was registered in 16 (20.5 %), poor prognosis according to IMDC score – in 33 (45.2 %) patients. Median follow-up was 9.7 (1–26) months.

Results. Median progression-free survival achieved 16.9 (95 % confidence intervals (CI) 12.1–20.6), overall survival – 20.8 (95 % CI 15.7–25.9) months. Objective response rate was 11 % (8/73); tumor control was reached in 93.2 % (68/73) of cases. Median objective response duration was 10.5 (4.3–16.8) months, tumor control duration – 10.0 (2.5–17.5) months. Any adverse events developed in 83.6 % (61/73), adverse events grade III–V – in 23.3 % (17/73) of cases. Most frequent AE grade III–IV were diarrhea (10 (13.6 %)) and arterial hypertension (6 (8.2 %)). Unacceptable toxicity demanded treatment cancellation in 4.2 % (3/73), therapy interruption – in 30.1 % (22/73) and dose reduction – in 32.9 % (24/73) of patients.

Conclusion. Unselected mRCC patients administered with combined targeted therapy in the real world practice were registered with similar survival, lower objective response rate, and better tolerability comparing with population assigned for lenvatinib plus everolimus in the randomized phase II trial.

About the Authors

M. I. Volkova
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

Department of Urology

24 Kashirskoe Shosse, Moscow 115478



A. M. Abdelgafur
Republican Clinical Oncology Dispensary, Ministry of Health of the Republic of Chuvashia
Russian Federation

31 Gladkova St., Cheboksary 428020, Republic of Chuvashia



M. T. Aivazov
Oncology Center No. 4, Moscow Department of Health
Russian Federation

7 Medikov St., Moscow 115304



Z. V. Amoev
Volga Regional Medical Center, Federal Biomedical Agency of Russia
Russian Federation

2 Nizhnevolzhskaya Naberezhnaya, Nizhny Novgorod 603001



K. G. Babina
Volgograd Regional Clinical Oncology Center
Russian Federation

78 im. Zemlyachki St., Volgograd 400138



P. S. Borisov
City Clinical Oncology Dispensary
Russian Federation

3/5 2nd Berezovya alleya, Saint Petersburg 197022



A. A. Vorontsovа
Oncology Center No. 4, Moscow Department of Health
Russian Federation

7 Medikov St., Moscow 115304



I. V. Evstigneeva
Tver Regional Clinical Oncology Dispensary
Russian Federation

57/37 15 let Oktyabrya St., Tver 170008



O. I. Evsyukova
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

Department of Urology

24 Kashirskoe Shosse, Moscow 115478



O. V. Zhelezin
Nizhny Novgorod Regional Clinical Oncology Dispensary
Russian Federation

11/1 Delovaya St., Nizhny Novgorod 603093



A. S. Kalpinsky
Р. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center, Ministry of Health of Russia
Russian Federation

3 2nd Botkinskiy Proezd, Moscow 125284



E. V. Karabina
Tula Regional Oncology Dispensary

201A Plekhanova St., Tula 300040



N. V. Kirdakova
City Clinical Oncology Hospital No. 1, Moscow Department of Health

17/1 Baumanskaya St., Moscow 105005



G. P. Kolesnikov
Moscow City Oncology Hospital No. 62, Department of Health of Moscow

27 Istra, Moscow region 143423



E. S. Kuzmina
Salekhard Regional Clinical Hospital

39 Mira St., Salekhard 629001



D. Kh. Latipova
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia

68 Leningradskaya St., Pesochny, Saint Petersburg 197758



R. V. Leonenkov
Saint Petersburg Clinical Scientific and Practical Center for Specialized Types of Medical Care (Oncology)

68A Leningradskaya St., Pesochny, Saint Petersburg 197758



M. R. Maturov
D.D. Pletnev City Clinical Hospital, Moscow Department of Health

32 11th Parkovaya St., Moscow 105077



A. V. Meskikh
D.D. Pletnev City Clinical Hospital, Moscow Department of Health

32 11th Parkovaya St., Moscow 105077



S. V. Mishugin
D.D. Pletnev City Clinical Hospital, Moscow Department of Health

32 11th Parkovaya St., Moscow 105077



E. G. Ovchinnikova
Nizhny Novgorod Regional Clinical Oncology Dispensary

11/1 Delovaya St., Nizhny Novgorod 603093



A. S. Olshanskaya
N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

Department of Urology

24 Kashirskoe Shosse, Moscow 115478



S. A. Protsenko
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia

68 Leningradskaya St., Pesochny, Saint Petersburg 197758



T. Yu. Semiglazova
N.N. Petrov National Medical Research Center of Oncology, Ministry of Health of Russia

68 Leningradskaya St., Pesochny, Saint Petersburg 197758



R. V. Smirnov
Vologda Regional Oncology Center

100 Sovetskiy Prospekt, Vologda 160012



E. A. Usynin
Tomsk National Research Medical Center of the Russian Academy of Sciences

5 Kooperativny Pereulok, Tomsk 634009



M. M. Fael
City Polyclinic No. 11, Moscow Department of Health

14 Kravchenko St., Moscow 119331



E. M. Cherniakova
Republican Oncology Dispensary Center

5 Lososinskoe Shosse, Petrozavodsk 185002



I. E. Shumskaya
City Clinical Oncology Hospital No. 1, Moscow Department of Health

201A Plekhanova St., Tula 300040



References

1. Motzer R.J., Escudier B., Oudard S. et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008;372(9637):449–56. DOI: 10.1016/S0140-6736(08)61039-9.

2. Motzer R.J., Escudier B., Oudard S. et al. Phase 3 trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer 2010;116(18): 4256–65. DOI: 10.1002/cncr.25219.

3. Ko J.J., Xie W., Kroeger N. et al. The International Metastatic Renal Cell Carcinoma Database Consortium model as a prognostic tool in patients with metastatic renal cell carcinoma previously treated with first-line targeted therapy: a population-based study. Lancet Oncol 2015;16(3):293–300. DOI: 10.1016/S1470-2045(14)71222-7.

4. Nosov D.A., Volkova M.I., Gladkov O.A. et al. Practical recommendations for the treatment of renal cell carcinoma. Malignant tumors: Practical recommendations of RUSSCO #3s2, 2018. Vol. 8. Pp. 440–446. (In Russ.).

5. NCCN Clinical Practice Guidelines in Oncology: Kidney Cancer, version 3.2019.

6. Escudier B. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2019. DOI: 10.1093/annonc/mdz056.

7. Guidelines on Renal Cell Carcinoma. European Association of Urology (EAU), 2018. Pp. 34–40.

8. Eisenhauer E.A., Therasse P., Bogaerts J. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45(2):228–47. DOI: 10.1016/j.ejca.2008.10.026.

9. http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.

10. IBM SPSS Statistics. Available at: http://www.predictive.ru/software/statistics.htm.

11. StatSoft. Available at: http://statsoft.ru.

12. Instruction on medical use of lenvatinib. Registration number ЛП-003398 (as amended on 06.12.2016). (In Russ.).

13. Instruction on medical use of everolimus. Registration number ЛП-002288. (In Russ.).

14. Grünwald V., Bavbek S.E. An international expanded-access programme of everolimus: addressing safety and efficacy in patients with metastatic renal cell carcinoma who progress after initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy. EJC 2012;48(3):324–32.

15. Motzer R. ESMO 2012 oral presentation; abstract LBA8_PR.

16. Rini B.I., Plimack E.R., Stus V. et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 2019;380(12):1116–27. DOI: 10.1056/NEJMoa1816714.

17. Rini B.I. Poster presentation at the European Society for Medical Oncology (ESMO) Congress. October 19–23, 2018. Munich, Germany. Poster 875P.

18. Choueiri T.K., Hessel C., Halabi S. et al. Cabozantinib versus sunitinib as initial therapy for metastatic renal cell carcinoma of intermediate or poor risk (Alliance A031203 CABOSUN randomised trial): Progression-free survival by independent review and overall survival update. Eur J Cancer. 2018;94:115–25. DOI: 10.1016/j.ejca.2018.02.012.

19. Mollica V., Di Nunno V., Gatto L. et al. Resistance to systemic agents in renal cell carcinoma predict and overcome genomic strategies adopted by tumor. Cancers 2019;11(6):830. DOI: 10.3390/cancers11060830.

20. De Lisi D., De Giorgi U., Lolli C. et al. Lenvatinib in the management of metastatic renal cell carcinoma: a promising combination therapy? Expert Opin Drug Metab Toxicol 2018;14(4):461–7. DOI: 10.1080/17425255.2018.1455826.

21. Boss D.S., Glen H., Beijnen J.H. et al. A phase I study of E7080, a multitargeted tyrosine kinase inhibitor, in patients with advanced solid tumours. Br J Cancer 2012;106(10):1598–604. DOI: 10.1038/bjc.2012.154.

22. Molina A.M., Hutson T.E., Larkin J. et al. A phase 1b clinical trial of the multitargeted tyrosine kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC). Cancer Chemother Pharmacol 2014;73(1):181–9. DOI: 10.1007/s00280-013-2339-y.

23. Motzer R.J., Hutson T.E., Ren M. et al. Independent assessment of lenvatinib plus everolimus in patients with metastatic renal cell carcinoma. Lancet Oncol 2016;17(1):e4–5. DOI: 10.1016/S14702045(15)00543-4.

24. Motzer R.J., Hutson T.E., Glen H. 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. DOI: 10.1016/S1470-2045(15)00290-9.

25. Motzer R., Hutson T., Glen H. et al. Randomized phase II, three-arm trial of lenvatinib (LEN), everolimus (EVE), and LEN+EVE in patients (pts) with metastatic renal cell carcinoma (mRCC). Poster ASCO, Chicago, IL, 1 June 2015. Available at: https://meetinglibrary.asco.org/record/109690/abstract.


Review

For citations:


Volkova M.I., Abdelgafur A.M., Aivazov M.T., Amoev Z.V., Babina K.G., Borisov P.S., Vorontsovа A.A., Evstigneeva I.V., Evsyukova O.I., Zhelezin O.V., Kalpinsky A.S., Karabina E.V., Kirdakova N.V., Kolesnikov G.P., Kuzmina E.S., Latipova D.Kh., Leonenkov R.V., Maturov M.R., Meskikh A.V., Mishugin S.V., Ovchinnikova E.G., Olshanskaya A.S., Protsenko S.A., Semiglazova T.Yu., Smirnov R.V., Usynin E.A., Fael M.M., Cherniakova E.M., Shumskaya I.E. Efficacy and safety of lenvatinib in combination with everolimus in metastatic renal cell carcinoma resistant to antiangiogenic targeted therapy: Russian multicenter observational study ROSLERCM. Cancer Urology. 2019;15(3):56-69. (In Russ.) https://doi.org/10.17650/1726-9776-2019-15-3-56-69

Views: 1056


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1726-9776 (Print)
ISSN 1996-1812 (Online)
X