How do clinicians choose between pazopanib and sunitinib as first-line therapy for advanced renal cell carcinoma? Beyond the Abstract

Although there has been significant progress over the last decade regarding development and approval of new treatments for patients with advanced renal cell carcinoma, including the tyrosine kinase inhibitors pazopanib and sunitinib1, clinical decision making in the ‘real world’ practice setting is often a poorly understood process. There is also disagreement in the rationale for selection of a particular drug, making the individualized patient treatment approach even more challenging for healthcare providers in this space.

Results of our retrospective analysis conducted to demonstrate the ‘real world’ effectiveness and safety of pazopanib suggested that outcomes in patients with advanced renal cell carcinoma (RCC) and treated with first-line therapy in a community oncology setting between November 1, 2009 to August 31, 2012 (N=177)2 were consistent with those observed in the pazopanib clinical trials3,4,5. In our study, patients from the US Oncology Network (USON) who were treated with first-line pazopanib had median progression-free survival (PFS) of 8.5 months, median overall survival (OS) was 22 months, and there was no treatment discontinuation (persistence) for a median of 151 days. The most common adverse events (AEs) observed were fatigue (56%), diarrhea (52%), vomiting (44%), and nausea (40%).

An exploratory objective in our study (not published in Vogelzang et al.2) was to evaluate the feasibility of comparing outcomes of the same patients receiving first-line pazopanib (N=177) to patients who were treated with first-line sunitinib (N=739)6. Propensity score 1:1 matching was conducted based on age, gender, and Heng disease risk (prognostic criteria)7, to identify corresponding patients in the two cohorts. The results (Table 1) demonstrate that all variables were matched, with the exception of Karnofsky performance status and neutrophil counts which were significantly different between the groups.

A separate, retrospective analysis, conducted in patients with advanced RCC from USON, evaluated clinical outcomes, dosing patterns, and toxicity of first-line sunitinib between June 1, 2007, and May 31, 2011 (N=134)8. Median PFS observed in this study was 7.5 months, median OS was 15.5 months, and objective response rate (ORR) was 16.4%. The median treatment duration was 4 cycles (range, 1-19). Overall, 113 patients discontinued sunitinib, mainly because of disease progression (45.1%) or toxicities (16.8%). Of all discontinuations, 77% occurred within the first 5 cycles. A total of 45 patients were dose-reduced, mostly because of toxicities (93%).

Separate and sequential ‘real world’ studies were conducted retrospectively in the community setting among similar patient populations to assess effectiveness of first-line treatment with pazopanib and sunitinib2,8. In the pazopanib study, clinical outcomes were consistent with those reported in the clinical trials. In the sunitinib study, clinical outcomes were inferior to those observed in the sunitinib clinical trials 9,10, which was attributed to more frequent dose reductions due to toxicities with patients discontinuing from sunitinib therapy sooner than in the clinical trials.

Although a phase III study comparing the efficacy of pazopanib versus sunitinib as first-line therapy for advanced/metastatic RCC demonstrated that pazopanib was non-inferior to sunitinib as indicated by a PFS HR of 1.047 (95% confidence interval [CI]: 0.8982-1.2195)5, there have been no comparative studies conducted to date which evaluates the ‘real-world’ clinical effectiveness and safety of pazopanib versus sunitinib in advanced RCC patients treated in the first-line setting. The preliminary results of the feasibility analysis we conducted suggests that further investigation may be warranted on the comparative outcomes in advanced RCC patients that receive these two agents in the ‘real world’ setting. Results of such comparative assessments may enable more informed decision-making by clinicians between the two first-line treatment choices in the community-based setting.

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1. Bukowski RM, Figlin RA, & Motzer RJ (Eds.). (2015). Renal cell carcinoma: Molecular targets and clinical applications (3rd ed.). New York, NY: Springer.

2. Vogelzang NJ, Hackshaw MD, Huston TE, et al. (2015). First-line and sequential use of pazopanib followed by mTOR inhibitor therapy among patients with advanced/metastatic renal cell carcinoma in a US community oncology setting. Clinical Genitourinary Cancer, 13(3), 210-7.

3. Sternberg CN, Davis ID, 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.

4. Sternberg CN, Hawkins RE, Wagstaff J, et al. A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: Final overall survival results and safety update. Eur J Cancer. 2013; 49(6):1289-96.

5. Motzer RJ, Hutson TE, Cella D, et al. Pazopanib versus sunitinib in metastatic renal-cell carcinoma. N Engl J Med. 2013; 369:722-31.

6. Data on File. Study 200210. 2014. Available at:

7. Heng DYC, 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(34):5794-99.

8. Schnadig ID, Hutson TE, Chung H. (2014). Dosing Patterns, Toxicity, and Outcomes in Patients Treated With First-Line Sunitinib for Advanced Renal Cell Carcinoma in Community-Based Practices. Clinical Genitourinary Cancer, 7673 (14), 126-8.

9. Motzer RJ, Hutson TE, Tomczak P et al. Sunitinib versus interferon alfa in metastatic renal cell carcinoma. N Engl J Med, 2007; 356(2):115-124.

10. Motzer RJ, Hutson TE, Tomczak P, et al. Overall Survival and Updated Results for Sunitinib Compared With Interferon Alfa in Patients With Metastatic Renal Cell Carcinoma. Journal of Clinical Oncology. 2009; 27:3584-3590.

Written by:

Nicholas J. Vogelzang
US Oncology Network, McKesson Specialty Health, The Woodlands, TX; Comprehensive Cancer Centers of Nevada, Las Vegas, NV.

Michelle D. Hackshaw
GlaxoSmithKline, Collegeville, PA.

Thomas E. Hutson
US Oncology Network, McKesson Specialty Health, The Woodlands, TX; Comprehensive Cancer Centers of Nevada, Las Vegas, NV; Texas Oncology-Baylor Sammons Cancer Center, Dallas, TX.

Eric Jonasch
University of Texas MD Anderson Cancer Center, Houston, TX.

Abstract: First-Line and Sequential Use of Pazopanib Followed by Mammalian Target of Rapamycin Inhibitor Therapy Among Patients With Advanced Renal Cell Carcinoma in a US Community Oncology Setting