pCODR Reimbursement Decision
|Xalkori (Original Submission)|
|Manufacturer||Pfizer Canada Inc.|
|pCODR Indication||Advanced Non-Small Cell Lung Cancer|
|pCODR Tumour Type||Lung|
|Funding Request||Patients with anaplastic lymphoma kinase-(ALK) positive advanced non-small cell lung cancer (NSCLC).|
|Submission Type||New Drug|
|Review Status||Notification to Implement Issued|
|Notification to Implement Date||2012-10-22|
|RD Interpretation of pERC Recommendation||Not recommended - clinical benefit insufficient/unclear.|
The pERC does not recommend funding crizotinib (Xalkori) for patients with ALK-positive advanced non-small cell lung cancer. The Committee made this recommendation because the Committee was not confident of the net clinical benefit of crizotinib due to limitations in the evidence available from clinical trials. Although the pertinent studies were appropriately conducted, pERC considered that the conclusions that could be drawn from non-randomized phase two studies were limited. While pERC was confident that crizotinib produced a tumour response, based on the observed magnitude of response, pERC was unable to determine how crizotinib compares with other treatments on outcomes important to decision-making such as overall survival, progression-free survival and quality of life.
Patients with ALK-positive advanced non-small cell lung cancer (NSCLC).
|RD Interpretation of Patient Population Requested vs Actual||
|Summary of pERC Deliberations - Clinical||
pERC deliberated upon the results of PROFILE 1001 and PROFILE 1005 but was not satisfied that the available evidence clearly demonstrated a net overall clinical benefit of treatment with crizotinib. While pERC considered that PROFILE 1001 and PROFILE 1005 were appropriately conducted non-randomized studies, the Committee concluded that the conclusions that can be drawn from these studies were limited. While pERC considered that the magnitude of objective tumour response observed with crizotinib in the two trials was substantial, pERC did not consider it sufficient evidence of effectiveness. pERC was concerned about the strength of the evidence due to inherent biases in such a study design. pERC further noted that results of a randomized controlled trial comparing crizotinib with standard of care in previously treated patients (PROFILE 1007) will soon be available and may provide additional clarity on the effectiveness of crizotinib. pERC noted that objective response rate is an uncertain surrogate for overall survival and that PROFILE 1001 and PROFILE 1005 did not provide any comparative evidence on overall survival or progression-free survival, which are standard outcomes in lung cancer. Furthermore, pERC found it difficult to assess the impact of crizotinib on patient-reported outcomes and quality of life as only abstract-level data were available and these could not be adequately appraised.
|Summary of pERC Deliberations - Safety||
pERC reviewed safety evidence for crizotinib from PROFILE 1001 and PROFILE 1005. pERC noted that there were a number of deaths due to hepatotoxicity and that QT prolongation had been observed. pERC noted that crizotinib generally appeared to be tolerated by patients with an acceptable toxicity profile; the most frequently observed adverse events included nausea, vomiting, dizziness and visual disturbances. However, given the lack of a comparator arm in PROFILE 1001 and PROFILE 1005, pERC considered the safety data to be preliminary.
|Summary of pERC Deliberations - Cost-effectiveness||
Overall, pERC considered that because of the limitations in the available clinical information for crizotinib from non-randomized studies, it was challenging to draw conclusions on the cost-effectiveness of crizotinib. In addition, when discussing the cost-effectiveness estimates, pERC noted that the EGP estimates were substantially larger than the manufacturer’s estimates but considered that the EGP estimates and assumptions were more realistic and clinically valid.
|Provincial Funding Report:|
|Final Recommendation Report:||
pCODR-pERC Final Recommendation report
|Final Clinical Guidance Report:||
pCODR Final Clinical Guidance report
|Final Economic Guidance Report:||
pCODR Final Economic Guidance report
†The information referenced on this page is compiled from publicly available documents published by pCODR and is available through the embedded links.