, Volume 31, Issue 1, pp 15–24 | Cite as

Pazopanib for the First-Line Treatment of Patients with Advanced and/or Metastatic Renal Cell Carcinoma

A NICE Single Technology Appraisal
  • Mary KilonzoEmail author
  • Jenni Hislop
  • Andrew Elders
  • Cynthia Fraser
  • Donald Bissett
  • Samuel McClinton
  • Graham Mowatt
  • Luke Vale
Review Article


The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of pazopanib hydrochloride (GlaxoSmithKline) to submit evidence of the clinical and cost effectiveness of the drug for the first-line treatment of advanced and/or metastatic renal cell carcinoma, as part of the Institute’s single technology appraisal (STA) process. The Aberdeen Health Technology Assessment Group were commissioned to act as the Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and NICE’s subsequent decisions. The objective of this paper is to summarize the independent review and critique of the evidence submitted for the consideration of the NICE Appraisal Committee and NICE’s subsequently issued guidance. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology based upon the manufacturer’s submission to NICE. The ERG also independently searched for relevant evidence and modified the manufacturer’s decision analytic model to examine the impact of altering some of the key assumptions. For progression-free survival (PFS), there was a statistically significant longer survival for pazopanib compared with placebo (as assessed by the ERG, based upon the original manufacturer submission with a clinical cut-off date of 23 May 2008) [median 11.1 vs. 2.8 months; hazard ratio (HR) 0.40; 95 % CI 0.27, 0.60]. Data from the indirect comparison suggested that pazopanib had a greater survival than interferon alpha (IFN-α) [HR 0.512; 95 % CI 0.326, 0.802] but provided no evidence of any difference compared with sunitinib (HR 0.949; 95 % CI 0.575, 1.568). With regard to overall survival, 64 % (n = 99) of patients in the pazopanib arm and 63 % (n = 49) of patients in the placebo arm had died and a total of 51 % (n = 40) of placebo patients had crossed over to receive pazopanib. Although data were provided on an intention-to-treat basis, crossover between therapies made such data difficult to interpret. There was no evidence of any statistically significant difference between pazopanib and best supportive care (HR 0.501; 95 % CI 0.136, 2.348). In the indirect comparison, there were no statistically significant differences between pazopanib and IFN-α (HR 0.627; 95 % CI 0.173, 2.269) or between pazopanib and sunitinib (HR 0.969; 95 % CI 0.359, 2.608). Based upon the work presented including a 12.5 % discount for pazopanib, sunitinib was extendedly dominated by a combination of pazopanib and IFN-α. As a consequence, the incremental cost per QALY for pazopanib versus IFN-α was £38,925. The results were not greatly altered over the range of univariate deterministic sensitivity analyses conducted by the manufacturer but pair-wise probabilistic sensitivity analyses suggested that given a threshold value of £30,000, there is a 54 % probability that pazopanib was preferred to sunitinib, 40 % chance against IFN-α and 47 % chance against best supportive care. The Appraisal Committee concluded that pazopanib should be recommended as a first-line treatment option for people with advanced renal cell carcinoma who have not received prior cytokine therapy and have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and if the manufacturer provides pazopanib with a 12.5 % discount on the list price and provides a possible future rebate linked to the outcome of the head-to-head COMPARZ trial, as agreed under the terms of the patient access scheme and to be confirmed when the COMPARZ trial data are made available.


Overall Survival Sunitinib Pazopanib Indirect Comparison Good Supportive Care 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment Programme (project number 08/220/01) and will be published as part of a compendium of ERG articles in Health Technology Assessment (HTA). See the HTA programme website for further project information ( This summary of the ERG report was compiled after the Appraisal Committee’s review. The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the Department of Health. Further acknowledgements are detailed in the ERG report [2]. This summary has not been externally peer reviewed by PharmacoEconomics.

Conflicts of interest

The authors declare no conflicts of interest.

Author contributions

Mary Kilonzo and Luke Vale conducted the critique of the manufacturer’s economic evaluation. Jenni Hislop and Graham Mowatt critiqued the manufacturer’s submission of effectiveness evidence. Donald Bissett and Samuel McClinton provided clinical advice and drafted the background and critique of the manufacturer’s decision problem. Andrew Elders critiqued the statistical methods used. Cynthia Fraser conducted the literature searches and critiqued the methods used for identifying relevant literature. All authors commented on drafts of the report. Mary Kilonzo can act as a guarantor for the overall content.


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Copyright information

© Springer International Publishing Switzerland 2012

Authors and Affiliations

  • Mary Kilonzo
    • 1
    Email author
  • Jenni Hislop
    • 2
  • Andrew Elders
    • 2
  • Cynthia Fraser
    • 2
  • Donald Bissett
    • 3
  • Samuel McClinton
    • 4
  • Graham Mowatt
    • 2
  • Luke Vale
    • 1
    • 2
  1. 1.Health Economics Research Unit, Institute of Applied Health SciencesUniversity of Aberdeen, Polwarth Building, ForesterhillAberdeenUK
  2. 2.Health Services Research, Unit Institute of Applied Health SciencesUniversity of AberdeenAberdeenUK
  3. 3.Department of Clinical OncologyAberdeen Royal InfirmaryAberdeenUK
  4. 4.Department of UrologyAberdeen Royal InfirmaryAberdeenUK

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