Advertisement

Phase 2 Multicenter Single-Arm Study of Second-Line Axitinib in Favorable Risk Patients with Metastatic Renal Cell Carcinoma: FavorAx

  • Ilya TsimafeyeuEmail author
  • Pavel Borisov
  • Ahmed Abdelgafur
  • Roman Leonenkov
  • Olga Novikova
  • Irina Guseva
  • Marina Demchenkova
  • Nadezhda Mikhailova
  • Andrey Semenov
  • Zakhar Yurmazov
  • Irina Sivunova
  • Madina Ramazanova
  • Sergey Gamayunov
  • Dmitry Kosov
  • Gennady Bratslavsky
Original Research Article

Abstract

Background

Targeted therapy with axitinib resulted in a greater objective response rate and prolonged progression-free survival (PFS) compared to sorafenib in patients with previously treated metastatic renal cell carcinoma (mRCC) in the phase 3 AXIS study, where 75% of patients had intermediate and poor International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk.

Objective

In this phase 2 study (FavorAx), we assessed the activity of axitinib in mRCC patients with a favorable risk and history of prior vascular endothelial growth factor receptor (VEGFR)-directed therapy.

Patients and Methods

Patients were required to have clear-cell mRCC, favorable risk according to IMDC criteria, and to have received first-line treatment with sunitinib or pazopanib. Prior treatment with other agents was not permitted. The primary endpoint of the study was 5 months PFS. Additional endpoints included response rate, safety, PFS, and overall survival (OS).

Results

A total of 21 patients were enrolled, 62% of whom were male. The mean age was 60 years. Eleven (52%) patients had two or more metastatic sites. 67% and 33% of patients received first-line sunitinib or pazopanib, respectively, with a median PFS of 17 months [95% confidence interval (CI), 14–20]. After a median follow-up of 25 months, the median PFS was 19 months (95% CI, 15–23). The current study did achieve its primary endpoint based on the 5-month PFS of 100%. The median OS was not yet reached. The 18 months OS rate was 85.7%. The objective response rate was 33% and one patient achieved a complete response. Seven patients had dose escalation of axitinib and four patients had dose reduction. Grade 3 adverse events were observed in 19% of cases. There was no discontinuation of therapy due to toxicity.

Conclusions

The encouraging PFS and favorable safety profile observed in the FavorAx study support the administration of axitinib in mRCC patients with favorable IMDC risk and a history of prior sunitinib or pazopanib.

Notes

Compliance with Ethical Standards

Funding

This study was funded by a grant from the Kidney Cancer Research Bureau. No external funding was used in the preparation of this manuscript.

Conflict of Interest

Ilya Tsimafeyeu, Pavel Borisov, Ahmed Abdelgafur, Roman Leonenkov, Olga Novikova, Irina Guseva, Marina Demchenkova, Nadezhda Mikhailova, Andrey Semenov, Zakhar Yurmazov, Irina Sivunova, Madina Ramazanova, Sergey Gamayunov, Dmitry Kosov, and Gennady Bratslavsky declare that they have no conflicts of interest that might be relevant to the contents of this manuscript.

References

  1. 1.
    Josephs D, Hutson TE, Cowey CL, et al. Efficacy and toxicity of sunitinib in patients with metastatic renal cell carcinoma with severe renal impairment or on haemodialysis. BJU Int. 2011;108:1279–83.CrossRefGoogle Scholar
  2. 2.
    Kaprin AD, Starinskiy VV, Petrova GV. Malignant tumors in Russia in 2016 (morbidity and mortality). Moscow, 2018, 250 pp. ISBN 978-5-85502-234-6.Google Scholar
  3. 3.
    Tsimafeyeu I, Zolotareva T, Varlamov S, et al. Five-year survival of patients with metastatic renal cell carcinoma in the Russian Federation: results from the RENSUR5 registry. Clin Genitourin Cancer. 2017;15(6):e1069–72.CrossRefGoogle Scholar
  4. 4.
    Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus Ipilimumab versus Sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277–90.CrossRefGoogle Scholar
  5. 5.
    Escudier B, Sharma P, McDermott DF, et al. CheckMate 025 randomized phase 3 study: outcomes by key baseline factors and prior therapy for nivolumab versus everolimus in advanced renal cell carcinoma. Eur Urol. 2017;72(6):962–71.CrossRefGoogle Scholar
  6. 6.
    Hu-Lowe DD, Zou HY, Grazzini ML, et al. Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res. 2008;14:7272–83.CrossRefGoogle Scholar
  7. 7.
    Hutson TE, Al-Shukri S, Stus VP, et al. Axitinib versus sorafenib in first-line metastatic renal cell carcinoma: overall survival from a randomized phase III trial. Clin Genitourin Cancer. 2017;15:72–6.CrossRefGoogle Scholar
  8. 8.
    Hutson TE, Lesovoy V, Al-Shukri S, et al. Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial. Lancet Oncol. 2013;14:1287–94.CrossRefGoogle Scholar
  9. 9.
    Rini BI, Escudier B, Tomczak P, et al. Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial. Lancet. 2011;378(9807):1931–9.CrossRefGoogle Scholar
  10. 10.
    Heng DY, Xie W, Regan MM, 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;27:5794–9.CrossRefGoogle Scholar
  11. 11.
    National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology: Kidney Cancer, version 3.2018.Google Scholar
  12. 12.
    Choueiri TK, Escudier B, Powles T, 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.CrossRefGoogle Scholar
  13. 13.
    Motzer RJ, Hutson TE, 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.CrossRefGoogle Scholar
  14. 14.
    Elaidi R, Harbaoui A, Beuselinck B, et al. Outcomes from second-line therapy in long-term responders to first-line tyrosine kinase inhibitor in clear-cell metastatic renal cell carcinoma. Ann Oncol. 2015;26:378–85.CrossRefGoogle Scholar
  15. 15.
    Davis ID, Xie W, Pezaro C, et al. Efficacy of second-line targeted therapy for renal cell carcinoma according to change from baseline in international metastatic renal cell carcinoma database consortium prognostic category. Eur Urol. 2017;71(6):970–8.CrossRefGoogle Scholar
  16. 16.
    Tsimafeyeu I, Snegovoy A, Varlamov S, et al. Everolimus in patients with metastatic renal cell carcinoma previously treated with bevacizumab: a prospective multicenter study CRAD001LRU02T. Target Oncol. 2015;10(3):423–7.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Ilya Tsimafeyeu
    • 1
    Email author
  • Pavel Borisov
    • 2
  • Ahmed Abdelgafur
    • 3
  • Roman Leonenkov
    • 4
  • Olga Novikova
    • 5
  • Irina Guseva
    • 6
  • Marina Demchenkova
    • 7
  • Nadezhda Mikhailova
    • 8
  • Andrey Semenov
    • 9
  • Zakhar Yurmazov
    • 10
  • Irina Sivunova
    • 11
  • Madina Ramazanova
    • 12
  • Sergey Gamayunov
    • 3
  • Dmitry Kosov
    • 13
  • Gennady Bratslavsky
    • 14
  1. 1.Kidney Cancer Research BureauMoscowRussia
  2. 2.City Clinical Oncology CenterSt. PetersburgRussia
  3. 3.Chuvashia Republican Cancer CenterCheboksaryRussia
  4. 4.St. Petersburg City Cancer CenterSt. PetersburgRussia
  5. 5.Khabarovsk Regional Cancer CenterKhabarovskRussia
  6. 6.Penza Regional Cancer CenterPenzaRussia
  7. 7.Irkutsk Regional Cancer CenterIrkutskRussia
  8. 8.Tatarstan Republican Cancer CenterKazanRussia
  9. 9.Ivanovo Regional Cancer CenterIvanovoRussia
  10. 10.Cancer Research InstituteTomskRussia
  11. 11.Kamchatka Regional Cancer CenterPetropavlovsk-KamchatskyRussia
  12. 12.Kirov Regional Cancer CenterKirovRussia
  13. 13.Aston Health Contract Research OrganizationMoscowRussia
  14. 14.Upstate Cancer CenterSUNY Upstate Medical UniversitySyracuseUSA

Personalised recommendations