TY - JOUR
T1 - Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS)
T2 - A randomised phase 3 trial
AU - Rini, Brian I.
AU - Escudier, Bernard
AU - Tomczak, Piotr
AU - Kaprin, Andrey
AU - Szczylik, Cezary
AU - Hutson, Thomas E.
AU - Michaelson, M. Dror
AU - Gorbunova, Vera A.
AU - Gore, Martin E.
AU - Rusakov, Igor G.
AU - Negrier, Sylvie
AU - Ou, Yen Chuan
AU - Castellano, Daniel
AU - Lim, Ho Yeong
AU - Uemura, Hirotsugu
AU - Tarazi, Jamal
AU - Cella, David
AU - Chen, Connie
AU - Rosbrook, Brad
AU - Kim, Sinil
AU - Motzer, Robert J.
N1 - Funding Information:
The study was sponsored by Pfizer Inc. We thank Helen Bhattacharyya, of Pfizer Inc, Global Outcomes Research, for assistance with patient-reported outcomes statistical analysis. Editorial assistance was provided by Larry Rosenberg and Joanna Bloom of UBC Scientific Solutions, and was funded by Pfizer Inc.
Funding Information:
BIR has served as a consultant for and received research funding from Pfizer. DCe has served as a consultant for and received research funding from Pfizer. MEG has served on the speakers' bureau and as an adviser for Bayer and Pfizer. TEH has served as a consultant for and received honoraria and research funding from AVEO, Bayer, Genentech, GlaxoSmithKline, and Pfizer. RJM has served as a consultant for Pfizer. SN has served as a consultant for Pfizer and Roche, and has received honoraria from Novartis and Pfizer and research funding from GlaxoSmithKline. BE has received honoraria from AVEO, Bayer, GlaxoSmithKline, Novartis, and Pfizer. CS has served on an advisory board for Pfizer. JT, CC, BR, and SK are employed by and own stock in Pfizer. AK, DCa, VG, IR, HYL, YCO, HU, MDM, and PT declare that they have no conflicts of interest.
PY - 2011
Y1 - 2011
N2 - The treatment of advanced renal cell carcinoma has been revolutionised by targeted therapy with drugs that block angiogenesis. So far, no phase 3 randomised trials comparing the effectiveness of one targeted agent against another have been reported. We did a randomised phase 3 study comparing axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor (VEGF) receptors, with sorafenib, an approved VEGF receptor inhibitor, as second-line therapy in patients with metastatic renal cell cancer. We included patients coming from 175 sites (hospitals and outpatient clinics) in 22 countries aged 18 years or older with confirmed renal clear-cell carcinoma who progressed despite first-line therapy containing sunitinib, bevacizumab plus interferon-alfa, temsirolimus, or cytokines. Patients were stratified according to Eastern Cooperative Oncology Group performance status and type of previous treatment and then randomly assigned (1:1) to either axitinib (5 mg twice daily) or sorafenib (400 mg twice daily). Axitinib dose increases to 7 mg and then to 10 mg, twice daily, were allowed for those patients without hypertension or adverse reactions above grade 2. Participants were not masked to study treatment. The primary endpoint was progression-free survival (PFS) and was assessed by a masked, independent radiology review and analysed by intention to treat. This trial was registered on ClinicalTrials.gov, number NCT00678392. A total of 723 patients were enrolled and randomly assigned to receive axitinib (n=361) or sorafenib (n=362). The median PFS was 6·7 months with axitinib compared to 4·7 months with sorafenib (hazard ratio 0·665; 95 CI 0·544-0·812; one-sided p<0·0001). Treatment was discontinued because of toxic effects in 14 (4) of 359 patients treated with axitinib and 29 (8) of 355 patients treated with sorafenib. The most common adverse events were diarrhoea, hypertension, and fatigue in the axitinib arm, and diarrhoea, palmar-plantar erythrodysaesthesia, and alopecia in the sorafenib arm. Axitinib resulted in significantly longer PFS compared with sorafenib. Axitinib is a treatment option for second-line therapy of advanced renal cell carcinoma. Pfizer Inc.
AB - The treatment of advanced renal cell carcinoma has been revolutionised by targeted therapy with drugs that block angiogenesis. So far, no phase 3 randomised trials comparing the effectiveness of one targeted agent against another have been reported. We did a randomised phase 3 study comparing axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor (VEGF) receptors, with sorafenib, an approved VEGF receptor inhibitor, as second-line therapy in patients with metastatic renal cell cancer. We included patients coming from 175 sites (hospitals and outpatient clinics) in 22 countries aged 18 years or older with confirmed renal clear-cell carcinoma who progressed despite first-line therapy containing sunitinib, bevacizumab plus interferon-alfa, temsirolimus, or cytokines. Patients were stratified according to Eastern Cooperative Oncology Group performance status and type of previous treatment and then randomly assigned (1:1) to either axitinib (5 mg twice daily) or sorafenib (400 mg twice daily). Axitinib dose increases to 7 mg and then to 10 mg, twice daily, were allowed for those patients without hypertension or adverse reactions above grade 2. Participants were not masked to study treatment. The primary endpoint was progression-free survival (PFS) and was assessed by a masked, independent radiology review and analysed by intention to treat. This trial was registered on ClinicalTrials.gov, number NCT00678392. A total of 723 patients were enrolled and randomly assigned to receive axitinib (n=361) or sorafenib (n=362). The median PFS was 6·7 months with axitinib compared to 4·7 months with sorafenib (hazard ratio 0·665; 95 CI 0·544-0·812; one-sided p<0·0001). Treatment was discontinued because of toxic effects in 14 (4) of 359 patients treated with axitinib and 29 (8) of 355 patients treated with sorafenib. The most common adverse events were diarrhoea, hypertension, and fatigue in the axitinib arm, and diarrhoea, palmar-plantar erythrodysaesthesia, and alopecia in the sorafenib arm. Axitinib resulted in significantly longer PFS compared with sorafenib. Axitinib is a treatment option for second-line therapy of advanced renal cell carcinoma. Pfizer Inc.
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U2 - 10.1016/S0140-6736(11)61613-9
DO - 10.1016/S0140-6736(11)61613-9
M3 - Article
C2 - 22056247
AN - SCOPUS:82755183572
SN - 0140-6736
VL - 378
SP - 1931
EP - 1939
JO - The Lancet
JF - The Lancet
IS - 9807
ER -
