Efficiency and safety of the everolimus in patients with the generalized renal cell carcinoma (multicentral observational study)

Objective – to evaluate efficacy and safety of everolimus in Russian population of unselected patients with advanced renal cell carcinoma progressing after at least 1 line of anti-angiogenic targeted therapy.

Materials and methods. In observational multicenter study CRAD001LRU03 from 17.01.2012 to 31.03.2015 in 43 centers 226 patients with advanced renal cell carcinoma with documented progression on the background or after at least 1 line of anti-angiogenic targeted therapy were included. The survey was conducted on all patients according to the practice, everolimus therapy was administered in accordance with instructions to the drug.

Results. Objective response rate was 10 %, tumor control was achieved on 69.2 % of patients. Progression-free survival median – 7.8 months. Adverse events occurred in 44.7 % of patients, reached the III–IV severity of 9.3 %, were the reason for the cancellation of everolimus therapy in 2.2 % of cases. The most frequent complications of treatment were pneumonitis (n = 5 (2.2 %)) and anemia (n = 3 (1.3 %)).

Conclusion. The observational study confirms efficacy and favorable safety profile of everolimus mTOR inhibitor in the Russian unselected patients with advanced renal cell carcinoma with progression or intolerable toxicity against background of anti-angiogenic therapy.

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.

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.

3. Therasse P., Arbuck S.G., Eisenhauer E.A. et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 2000;92(3):205–16.

4. Motzer R.J., Bacik J., Schwartz L.H. et al. Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma. J Clin Oncol 2004;22(3):454–63.

5. Ljungberg B., Cowan N.C., Hanbury D.C. et al. EAU guidelines on renal cell carcinoma: the 2010 update. Eur Urol 2010;58(3): 398–406.

6. Escudier B., Kataja V., ESMO Guidelines Working Group. Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21 Suppl 5:v137–9.

7. de Reijke T.M., Bellmunt J., van Poppel H. et al. EORTC-GU group expert opinion on metastatic renal cell cancer. Eur J Cancer 2009;45:765–73.

8. Calvo E., Maroto P., del Muro X.G. et al. Updated recommendations from the Spanish Oncology Genitourinary Group on the treatment of advanced renal cell carcinoma. Cancer Metastasis Rev 2010;29 Suppl 1:1–10.

9. Patard J.J., Baumert H., Corréas J.M. et al. Recommendations onco-urology 2010: kidney cancer. Prog Urol 2010;20(Suppl 4):S319–39.

10. Алексеев Б.Я., Волкова М.И., Калпинский А.С. и др. Клинические рекомендации по диагностике и лечению рака почки. М., 2014. C. 35. [Alekseev B.Ya., Volkova M.I., Kalpinskiy A.S. Clinical guidelines for the diagnosis and treatment of kidney cancer. Moscow, 2014. P. 35. (In Russ.)].

11. 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;45:228–47.

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

13. Escudier B., Bellmunt J., Negrie S. et al. Phase III trial of bevacizumab plus interferon alfa-2a in patients with metastatic renal cell carcinoma (AVOREN): Final analysis of overall survival. J Clin Oncol 2010;28(13):2144–50.

14. Rini B., Halabi S., Rosenberg J. et al. Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal rell carcinoma: final results of CALGB 90206. J Clin Oncol 2010;28(13):2137–43.

15. Motzer R.J., Hutson T.E., Tomczak P. et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 2007;356(2):115–124.

16. Sternberg C.N., Davis I.D., Mardiak J. et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol 2010;28(6):1061–8.

17. Rini B.I., Escudier B., Tomczak P. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet 2011;378(9807):1931–9.

18. Motzer R.J., Alyasova A., Ye D. Phase II trial of second-line everolimus in patients with metastatic renal cell carcinoma (RECORD-4). Ann Oncol 2016;27(3):441–8.

19. 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.