Pazopanib versus sunitinib in metastatic renal-cell carcinoma

Robert J. Motzer, Thomas E. Hutson, David Cella, James Reeves, Robert Hawkins, Jun Guo, Paul Nathan, Michael Staehler, Paulde Souza, Jaime R Merchan, Ekaterini Boleti, Kate Fife, Jie Jin, Robert Jones, Hirotsugu Uemura, Ugo De Giorgi, Ulrika Harmenberg, Jinwan Wang, Cora N. Sternberg, Keith DeenLauren McCann, Michelle D. Hackshaw, Rocco Crescenzo, Lini N. Pandite, Toni K. Choueiri

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Abstract

BACKGROUND: Pazopanib and sunitinib provided a progression-free survival benefit, as compared with placebo or interferon, in previous phase 3 studies involving patients with metastatic renal-cell carcinoma. This phase 3, randomized trial compared the efficacy and safety of pazopanib and sunitinib as first-line therapy. METHODS: We randomly assigned 1110 patients with clear-cell, metastatic renal-cell carcinoma, in a 1:1 ratio, to receive a continuous dose of pazopanib (800 mg once daily; 557 patients) or sunitinib in 6-week cycles (50 mg once daily for 4 weeks, followed by 2 weeks without treatment; 553 patients). The primary end point was progression-free survival as assessed by independent review, and the study was powered to show the noninferiority of pazopanib versus sunitinib. Secondary end points included overall survival, safety, and quality of life. RESULTS: Pazopanib was noninferior to sunitinib with respect to progression-free survival (hazard ratio for progression of disease or death from any cause, 1.05; 95% confidence interval [CI], 0.90 to 1.22), meeting the predefined noninferiority margin (upper bound of the 95% confidence interval, <1.25). Overall survival was similar (hazard ratio for death with pazopanib, 0.91; 95% CI, 0.76 to 1.08). Patients treated with sunitinib, as compared with those treated with pazopanib, had a higher incidence of fatigue (63% vs. 55%), the hand-foot syndrome (50% vs. 29%), and thrombocytopenia (78% vs. 41%); patients treated with pazopanib had a higher incidence of increased levels of alanine aminotransferase (60%, vs. 43% with sunitinib). The mean change from baseline in 11 of 14 health-related quality-of-life domains, particularly those related to fatigue or soreness in the mouth, throat, hands, or feet, during the first 6 months of treatment favored pazopanib (P<0.05 for all 11 comparisons). CONCLUSIONS: Pazopanib and sunitinib have similar efficacy, but the safety and quality-of-life profiles favor pazopanib.

Original languageEnglish
Pages (from-to)722-731
Number of pages10
JournalNew England Journal of Medicine
Volume369
Issue number8
DOIs
StatePublished - Aug 28 2013

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Renal Cell Carcinoma
Disease-Free Survival
Quality of Life
Confidence Intervals
Safety
Fatigue
pazopanib
sunitinib
Hand-Foot Syndrome
Survival
Incidence
Pharynx
Alanine Transaminase
Thrombocytopenia
Interferons
Mouth
Disease Progression
Foot
Cause of Death
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Motzer, R. J., Hutson, T. E., Cella, D., Reeves, J., Hawkins, R., Guo, J., ... Choueiri, T. K. (2013). Pazopanib versus sunitinib in metastatic renal-cell carcinoma. New England Journal of Medicine, 369(8), 722-731. https://doi.org/10.1056/NEJMoa1303989

Pazopanib versus sunitinib in metastatic renal-cell carcinoma. / Motzer, Robert J.; Hutson, Thomas E.; Cella, David; Reeves, James; Hawkins, Robert; Guo, Jun; Nathan, Paul; Staehler, Michael; Souza, Paulde; Merchan, Jaime R; Boleti, Ekaterini; Fife, Kate; Jin, Jie; Jones, Robert; Uemura, Hirotsugu; De Giorgi, Ugo; Harmenberg, Ulrika; Wang, Jinwan; Sternberg, Cora N.; Deen, Keith; McCann, Lauren; Hackshaw, Michelle D.; Crescenzo, Rocco; Pandite, Lini N.; Choueiri, Toni K.

In: New England Journal of Medicine, Vol. 369, No. 8, 28.08.2013, p. 722-731.

Research output: Contribution to journalArticle

Motzer, RJ, Hutson, TE, Cella, D, Reeves, J, Hawkins, R, Guo, J, Nathan, P, Staehler, M, Souza, P, Merchan, JR, Boleti, E, Fife, K, Jin, J, Jones, R, Uemura, H, De Giorgi, U, Harmenberg, U, Wang, J, Sternberg, CN, Deen, K, McCann, L, Hackshaw, MD, Crescenzo, R, Pandite, LN & Choueiri, TK 2013, 'Pazopanib versus sunitinib in metastatic renal-cell carcinoma', New England Journal of Medicine, vol. 369, no. 8, pp. 722-731. https://doi.org/10.1056/NEJMoa1303989
Motzer RJ, Hutson TE, Cella D, Reeves J, Hawkins R, Guo J et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. New England Journal of Medicine. 2013 Aug 28;369(8):722-731. https://doi.org/10.1056/NEJMoa1303989
Motzer, Robert J. ; Hutson, Thomas E. ; Cella, David ; Reeves, James ; Hawkins, Robert ; Guo, Jun ; Nathan, Paul ; Staehler, Michael ; Souza, Paulde ; Merchan, Jaime R ; Boleti, Ekaterini ; Fife, Kate ; Jin, Jie ; Jones, Robert ; Uemura, Hirotsugu ; De Giorgi, Ugo ; Harmenberg, Ulrika ; Wang, Jinwan ; Sternberg, Cora N. ; Deen, Keith ; McCann, Lauren ; Hackshaw, Michelle D. ; Crescenzo, Rocco ; Pandite, Lini N. ; Choueiri, Toni K. / Pazopanib versus sunitinib in metastatic renal-cell carcinoma. In: New England Journal of Medicine. 2013 ; Vol. 369, No. 8. pp. 722-731.
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abstract = "BACKGROUND: Pazopanib and sunitinib provided a progression-free survival benefit, as compared with placebo or interferon, in previous phase 3 studies involving patients with metastatic renal-cell carcinoma. This phase 3, randomized trial compared the efficacy and safety of pazopanib and sunitinib as first-line therapy. METHODS: We randomly assigned 1110 patients with clear-cell, metastatic renal-cell carcinoma, in a 1:1 ratio, to receive a continuous dose of pazopanib (800 mg once daily; 557 patients) or sunitinib in 6-week cycles (50 mg once daily for 4 weeks, followed by 2 weeks without treatment; 553 patients). The primary end point was progression-free survival as assessed by independent review, and the study was powered to show the noninferiority of pazopanib versus sunitinib. Secondary end points included overall survival, safety, and quality of life. RESULTS: Pazopanib was noninferior to sunitinib with respect to progression-free survival (hazard ratio for progression of disease or death from any cause, 1.05; 95{\%} confidence interval [CI], 0.90 to 1.22), meeting the predefined noninferiority margin (upper bound of the 95{\%} confidence interval, <1.25). Overall survival was similar (hazard ratio for death with pazopanib, 0.91; 95{\%} CI, 0.76 to 1.08). Patients treated with sunitinib, as compared with those treated with pazopanib, had a higher incidence of fatigue (63{\%} vs. 55{\%}), the hand-foot syndrome (50{\%} vs. 29{\%}), and thrombocytopenia (78{\%} vs. 41{\%}); patients treated with pazopanib had a higher incidence of increased levels of alanine aminotransferase (60{\%}, vs. 43{\%} with sunitinib). The mean change from baseline in 11 of 14 health-related quality-of-life domains, particularly those related to fatigue or soreness in the mouth, throat, hands, or feet, during the first 6 months of treatment favored pazopanib (P<0.05 for all 11 comparisons). CONCLUSIONS: Pazopanib and sunitinib have similar efficacy, but the safety and quality-of-life profiles favor pazopanib.",
author = "Motzer, {Robert J.} and Hutson, {Thomas E.} and David Cella and James Reeves and Robert Hawkins and Jun Guo and Paul Nathan and Michael Staehler and Paulde Souza and Merchan, {Jaime R} and Ekaterini Boleti and Kate Fife and Jie Jin and Robert Jones and Hirotsugu Uemura and {De Giorgi}, Ugo and Ulrika Harmenberg and Jinwan Wang and Sternberg, {Cora N.} and Keith Deen and Lauren McCann and Hackshaw, {Michelle D.} and Rocco Crescenzo and Pandite, {Lini N.} and Choueiri, {Toni K.}",
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T1 - Pazopanib versus sunitinib in metastatic renal-cell carcinoma

AU - Motzer, Robert J.

AU - Hutson, Thomas E.

AU - Cella, David

AU - Reeves, James

AU - Hawkins, Robert

AU - Guo, Jun

AU - Nathan, Paul

AU - Staehler, Michael

AU - Souza, Paulde

AU - Merchan, Jaime R

AU - Boleti, Ekaterini

AU - Fife, Kate

AU - Jin, Jie

AU - Jones, Robert

AU - Uemura, Hirotsugu

AU - De Giorgi, Ugo

AU - Harmenberg, Ulrika

AU - Wang, Jinwan

AU - Sternberg, Cora N.

AU - Deen, Keith

AU - McCann, Lauren

AU - Hackshaw, Michelle D.

AU - Crescenzo, Rocco

AU - Pandite, Lini N.

AU - Choueiri, Toni K.

PY - 2013/8/28

Y1 - 2013/8/28

N2 - BACKGROUND: Pazopanib and sunitinib provided a progression-free survival benefit, as compared with placebo or interferon, in previous phase 3 studies involving patients with metastatic renal-cell carcinoma. This phase 3, randomized trial compared the efficacy and safety of pazopanib and sunitinib as first-line therapy. METHODS: We randomly assigned 1110 patients with clear-cell, metastatic renal-cell carcinoma, in a 1:1 ratio, to receive a continuous dose of pazopanib (800 mg once daily; 557 patients) or sunitinib in 6-week cycles (50 mg once daily for 4 weeks, followed by 2 weeks without treatment; 553 patients). The primary end point was progression-free survival as assessed by independent review, and the study was powered to show the noninferiority of pazopanib versus sunitinib. Secondary end points included overall survival, safety, and quality of life. RESULTS: Pazopanib was noninferior to sunitinib with respect to progression-free survival (hazard ratio for progression of disease or death from any cause, 1.05; 95% confidence interval [CI], 0.90 to 1.22), meeting the predefined noninferiority margin (upper bound of the 95% confidence interval, <1.25). Overall survival was similar (hazard ratio for death with pazopanib, 0.91; 95% CI, 0.76 to 1.08). Patients treated with sunitinib, as compared with those treated with pazopanib, had a higher incidence of fatigue (63% vs. 55%), the hand-foot syndrome (50% vs. 29%), and thrombocytopenia (78% vs. 41%); patients treated with pazopanib had a higher incidence of increased levels of alanine aminotransferase (60%, vs. 43% with sunitinib). The mean change from baseline in 11 of 14 health-related quality-of-life domains, particularly those related to fatigue or soreness in the mouth, throat, hands, or feet, during the first 6 months of treatment favored pazopanib (P<0.05 for all 11 comparisons). CONCLUSIONS: Pazopanib and sunitinib have similar efficacy, but the safety and quality-of-life profiles favor pazopanib.

AB - BACKGROUND: Pazopanib and sunitinib provided a progression-free survival benefit, as compared with placebo or interferon, in previous phase 3 studies involving patients with metastatic renal-cell carcinoma. This phase 3, randomized trial compared the efficacy and safety of pazopanib and sunitinib as first-line therapy. METHODS: We randomly assigned 1110 patients with clear-cell, metastatic renal-cell carcinoma, in a 1:1 ratio, to receive a continuous dose of pazopanib (800 mg once daily; 557 patients) or sunitinib in 6-week cycles (50 mg once daily for 4 weeks, followed by 2 weeks without treatment; 553 patients). The primary end point was progression-free survival as assessed by independent review, and the study was powered to show the noninferiority of pazopanib versus sunitinib. Secondary end points included overall survival, safety, and quality of life. RESULTS: Pazopanib was noninferior to sunitinib with respect to progression-free survival (hazard ratio for progression of disease or death from any cause, 1.05; 95% confidence interval [CI], 0.90 to 1.22), meeting the predefined noninferiority margin (upper bound of the 95% confidence interval, <1.25). Overall survival was similar (hazard ratio for death with pazopanib, 0.91; 95% CI, 0.76 to 1.08). Patients treated with sunitinib, as compared with those treated with pazopanib, had a higher incidence of fatigue (63% vs. 55%), the hand-foot syndrome (50% vs. 29%), and thrombocytopenia (78% vs. 41%); patients treated with pazopanib had a higher incidence of increased levels of alanine aminotransferase (60%, vs. 43% with sunitinib). The mean change from baseline in 11 of 14 health-related quality-of-life domains, particularly those related to fatigue or soreness in the mouth, throat, hands, or feet, during the first 6 months of treatment favored pazopanib (P<0.05 for all 11 comparisons). CONCLUSIONS: Pazopanib and sunitinib have similar efficacy, but the safety and quality-of-life profiles favor pazopanib.

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