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pCODR Reimbursement Decision




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  Votrient (Original Submission)
Generic Name Pazopanib Hydrochloride
Manufacturer GlaxoSmithKline Inc.
pCODR Indication Metastatic Renal Cell Carcinoma
pCODR Tumour Type Genitourinary
Funding Request First-line therapy in patients with metastatic renal cell (clear cell) carcinoma who have a Memorial Sloan Kettering prognostic score of favourable or intermediate risk.
Submission Date 2011-07-14
Submission Type New Drug
Review Status Notification to Implement Issued
Recommendation Date 2012-01-05
Notification to Implement Date 2012-01-20
RD Interpretation of pERC Recommendation Recommended - with criteria/conditions.
pERC Recommendation

The pCODR Expert Review Committee (pERC) recommends funding pazopanib hydrochloride (Votrient) for patients with advanced or metastatic clear cell renal carcinoma who, based on the mutual assessment of the treating physician and the patient, are unable to tolerate ongoing use of an effective dose of sunitinib. Funding in a broader patient population was not recommended because there is too much uncertainty, due to the lack of direct evidence from randomized comparative trials, that the effectiveness of pazopanib is similar to sunitinib; however, there is a need for other options among patients unable to tolerate sunitinib. Therefore, while current evidence is insufficient to recommend funding broadly, from a clinical perspective, it suggests that pazopanib could have similar efficacy, better tolerability and may be cost-effective relative to sunitinib, assuming similar pricing and standard dosing of the two therapies. This led pERC to recommend pazopanib for the defined population of patients who are unable to tolerate sunitinib.

Patient Population

Patients with advanced or metastatic clear cell renal carcinoma who are unable to tolerate ongoing use of an effective dose of sunitinib.

RD Interpretation of Patient Population Requested vs Actual

Limited

Summary of pERC Deliberations - Clinical

Given the lack of a relevant comparator in the main pazopanib study, pERC placed progression-free survival and overall survival results from Study VEG105192 in the context of results from a randomized controlled trial comparing sunitinib with interferon (Motzer 2007) as well as an indirect comparison that informed the clinical effect estimates in the economic analysis (Kilonzo 2010). This led pERC to consider the possibility that pazopanib and sunitinib may have similar efficacy. The Committee had concerns that interpretations based on cross-trial and indirect comparisons are uncertain on the magnitude and direction of benefit. pERC discussed that results from an ongoing study comparing pazopanib and sunitinib (COMPARZ) will provide more certainty regarding the relative effectiveness of the two treatments. Given the uncertainty in the effectiveness of pazopanib relative to other available targeted therapies used to treat advanced or metastatic renal cell carcinoma, pERC did not support funding pazopanib as a first-line treatment in all patients with advanced or metastatic renal cell carcinoma. However, pERC determined that when considering need and the availability of effective alternatives, there may be a smaller patient population that could benefit from access to pazopanib. Upon reconsideration of the pERC Initial Recommendation, the Committee discussed feedback from the manufacturer but noted that none of this feedback was able to reduce the uncertainty that pERC experienced in interpreting the evidence associated with pazopanib. pERC also deliberated upon the potential use of pazopanib in patients whose disease has progressed while taking sunitinib. It was noted that there were no randomized controlled trials evaluating pazopanib in this patient population. In addition, the Committee discussed comments from the Provincial Advisory Group that use of pazopanib following other tyrosine kinase inhibitors may impact adoption feasibility by increasing the budget impact of pazopanib. pERC noted that the current standard of care for second-line treatment of advanced or metastatic renal cell carcinoma is everolimus and concluded that there was insufficient reason to support pazopanib use in this setting as everolimus has been studied in patients with metastatic renal cell carcinoma with disease progression on a tyrosine kinase inhibitor.

Summary of pERC Deliberations - Safety

The Committee also interpreted safety data on pazopanib in the context of cross-trial and indirect comparisons with sunitinib and encountered similar uncertainty. The Committee noted that in an indirect comparison, pazopanib had statistically significantly less fatigue compared with sunitinib but that no other statistically significant differences in adverse events were reported. This led pERC to consider the possibility that pazopanib may have a more favourable side effect profile. In further reflecting on the safety of pazopanib and the current clinical context, the Committee noted that side effects such as hand- foot syndrome are associated with sunitinib and are a concern to patients. In the randomized controlled trial comparing pazopanib with placebo, the proportion of patients reporting hand-foot syndrome was less than 10%, which the Committee considered to be low. Therefore, pERC considered that providing pazopanib as an option in patients who are intolerant to sunitinib may meet a specific need for some patients and would align with patient-expressed values of having more treatment options and potentially less side effects than with currently available drugs. Upon reconsideration of the pERC Initial Recommendation, the Committee discussed patient advocacy group feedback regarding how intolerance to sunitinib could best be defined for funding purposes and how patient care could be impacted by the definition of intolerance. pERC noted that it was important that the determination of intolerance to sunitinib be based on the assessment of the treating physician, taking into consideration the concerns of the patient.

Summary of pERC Deliberations - Cost-effectiveness

pERC deliberated upon the cost-effectiveness of pazopanib. pERC determined that due to the uncertainty of the clinical effectiveness of pazopanib relative to sunitinib, the cost-effectiveness of pazopanib was also uncertain. However, when considering a number of estimates and ranges of cost- effectiveness including the manufacturer’s estimate of $57,309 per quality-adjusted life year for pazopanib versus sunitinib, pERC recognized that there is a possibility that pazopanib could be cost-effective as a first-line therapy. This estimate was based on a confidential price for pazopanib and a 10% reduction from the list price for sunitinib. The Committee noted that the possibility of confidential pricing arrangements for pazopanib and sunitinib introduced further uncertainty into the cost-effectiveness estimates. The Committee recognized that the cost-effectiveness estimates in the economic evaluation did not apply to patients who are intolerant to sunitinib. They discussed that there is currently no clinical data on the effectiveness of pazopanib in these patients but also concluded that there is limited merit in trying to collect these data simply to inform this recommendation.

Provincial Funding Report: pCODR Provincial Funding Summary Report  pCODR Provincial Funding Summary report
https://www.cadth.ca/sites/default/files/pcodr/pcodr-provfund_votrient-mrcc.pdf
Final Recommendation Report: pCODR-pERC Final Recommendation report  pCODR-pERC Final Recommendation report
https://www.cadth.ca/sites/default/files/pcodr/pcodr-votrientmrcc-fn-rec.pdf
Final Clinical Guidance Report: pCODR Final Clinical Guidance Report  pCODR Final Clinical Guidance report
https://www.cadth.ca/sites/default/files/pcodr/pcodr-votrientmrcc-fn-cgr.pdf
Final Economic Guidance Report: pCODR Final Economic Guidance report  pCODR Final Economic Guidance report
https://www.cadth.ca/sites/default/files/pcodr/pcodr-votrientmrcc-fn-egr.pdf

†The information referenced on this page is compiled from publicly available documents published by pCODR and is available through the embedded links.


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