Ilya Tsimafeyeu1, Pavel Borisov2, Ahmed Abdelgafur3, Roman Leonenkov4, Olga Novikova5, Irina Guseva6, Marina Demchenkova7, Nadezhda Mikhailova8, Andrey Semenov9, Zakhar Yurmazov10, Irina Sivunova11, Madina Ramazanova12, Sergey Gamayunov3, Dmitry Kosov13, Gennady Bratslavsky14. 1. Kidney Cancer Research Bureau, Mayakovskogo pereulok, 2, 109147, Moscow, Russia. tsimafeyeu@gmail.com. 2. City Clinical Oncology Center, St. Petersburg, Russia. 3. Chuvashia Republican Cancer Center, Cheboksary, Russia. 4. St. Petersburg City Cancer Center, St. Petersburg, Russia. 5. Khabarovsk Regional Cancer Center, Khabarovsk, Russia. 6. Penza Regional Cancer Center, Penza, Russia. 7. Irkutsk Regional Cancer Center, Irkutsk, Russia. 8. Tatarstan Republican Cancer Center, Kazan, Russia. 9. Ivanovo Regional Cancer Center, Ivanovo, Russia. 10. Cancer Research Institute, Tomsk, Russia. 11. Kamchatka Regional Cancer Center, Petropavlovsk-Kamchatsky, Russia. 12. Kirov Regional Cancer Center, Kirov, Russia. 13. Aston Health Contract Research Organization, Moscow, Russia. 14. Upstate Cancer Center, SUNY Upstate Medical University, Syracuse, NY, USA.
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.
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.
Authors: Bernard Escudier; Padmanee Sharma; David F McDermott; Saby George; Hans J Hammers; Sandhya Srinivas; Scott S Tykodi; Jeffrey A Sosman; Giuseppe Procopio; Elizabeth R Plimack; Daniel Castellano; Howard Gurney; Frede Donskov; Katriina Peltola; John Wagstaff; Thomas C Gauler; Takeshi Ueda; Huanyu Zhao; Ian M Waxman; Robert J Motzer Journal: Eur Urol Date: 2017-03-03 Impact factor: 20.096
Authors: Thomas E Hutson; Vladimir Lesovoy; Salman Al-Shukri; Viktor P Stus; Oleg N Lipatov; Angel H Bair; Brad Rosbrook; Connie Chen; Sinil Kim; Nicholas J Vogelzang Journal: Lancet Oncol Date: 2013-10-25 Impact factor: 41.316
Authors: Toni K Choueiri; Bernard Escudier; Thomas Powles; Nizar M Tannir; Paul N Mainwaring; Brian I Rini; Hans J Hammers; Frede Donskov; Bruce J Roth; Katriina Peltola; Jae Lyun Lee; Daniel Y C Heng; Manuela Schmidinger; Neeraj Agarwal; Cora N Sternberg; David F McDermott; Dana T Aftab; Colin Hessel; Christian Scheffold; Gisela Schwab; Thomas E Hutson; Sumanta Pal; Robert J Motzer Journal: Lancet Oncol Date: 2016-06-05 Impact factor: 41.316
Authors: Robert J Motzer; Thomas E Hutson; Hilary Glen; M Dror Michaelson; Ana Molina; Timothy Eisen; Jacek Jassem; Jakub Zolnierek; Jose Pablo Maroto; Begoña Mellado; Bohuslav Melichar; Jiri Tomasek; Alton Kremer; Han-Joo Kim; Karen Wood; Corina Dutcus; James Larkin Journal: Lancet Oncol Date: 2015-10-22 Impact factor: 41.316
Authors: Thomas E Hutson; Salman Al-Shukri; Viktor P Stus; Oleg N Lipatov; Yaroslav Shparyk; Angel H Bair; Brad Rosbrook; Glen I Andrews; Nicholas J Vogelzang Journal: Clin Genitourin Cancer Date: 2016-05-27 Impact factor: 2.872
Authors: Robert J Motzer; Nizar M Tannir; David F McDermott; Osvaldo Arén Frontera; Bohuslav Melichar; Toni K Choueiri; Elizabeth R Plimack; Philippe Barthélémy; Camillo Porta; Saby George; Thomas Powles; Frede Donskov; Victoria Neiman; Christian K Kollmannsberger; Pamela Salman; Howard Gurney; Robert Hawkins; Alain Ravaud; Marc-Oliver Grimm; Sergio Bracarda; Carlos H Barrios; Yoshihiko Tomita; Daniel Castellano; Brian I Rini; Allen C Chen; Sabeen Mekan; M Brent McHenry; Megan Wind-Rotolo; Justin Doan; Padmanee Sharma; Hans J Hammers; Bernard Escudier Journal: N Engl J Med Date: 2018-03-21 Impact factor: 91.245
Authors: Debra Josephs; Thomas E Hutson; Charles L Cowey; Lisa M Pickering; James M Larkin; Martin E Gore; Mieke Van Hemelrijck; David F McDermott; Thomas Powles; Paramit Chowdhury; Chris Karapetis; Peter G Harper; Toni K Choueiri; Simon Chowdhury Journal: BJU Int Date: 2011-01-18 Impact factor: 5.588
Authors: Dana D Hu-Lowe; Helen Y Zou; Maren L Grazzini; Max E Hallin; Grant R Wickman; Karin Amundson; Jeffrey H Chen; David A Rewolinski; Shinji Yamazaki; Ellen Y Wu; Michele A McTigue; Brion W Murray; Robert S Kania; Patrick O'Connor; David R Shalinsky; Steve L Bender Journal: Clin Cancer Res Date: 2008-11-15 Impact factor: 12.531