Bevacizumab for metastatic colorectal cancer: a NICE single technology appraisal

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of bevacizumab (Roche Products) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of patients with metastatic colorectal cancer (mCRC), as part of the Institute's Single Technology Appraisal (STA) process. The School of Health and Related Research (ScHARR) at the University of Sheffield was commissioned to act as the Evidence Review Group (ERG). This paper provides a description of the company submission, the ERG review and NICE's subsequent decisions. The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology provided within 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. The main clinical effectiveness data were derived from a phase III, multicentre, multinational, two-arm, randomized, open-label study with the primary objective of confirming the non-inferiority of oxaliplatin plus capecitabine (XELOX) compared with oxaliplatin plus 5-fluorouracil and folinic acid (FOLFOX-4) in adult patients with histologically confirmed mCRC who had not previously been treated. The ERG considered that the NO16966 trial was of reasonable methodological quality and demonstrated a significant improvement in both progression-free and overall survival when bevacizumab is added to either XELOX or FOLFOX-4. The ERG considered that the size of the actual treatment effect of bevacizumab was uncertain due to trial design limitations, imbalance of a known prognostic factor, relatively short treatment duration compared with that allowed within the trial protocol, and interpretation of the statistical analyses. The manufacturer's submission included a de novo economic evaluation using a cost-effectiveness model built in Microsoft® Excel. The ERG believed that the modelling structure employed was appropriate but highlighted several areas of uncertainty that had the potential to have a significant impact on the resulting incremental cost-effectiveness ratios (ICERs). The areas of uncertainty identified by the ERG included whether chemotherapy would be administered continuously or intermittently, patient access scheme (PAS) costs and uptake, survival that was dependent on the statistical analyses used, and the likely duration of continued treatment with bevacizumab after cessation of oxaliplatin and the efficacy associated with continuation. The STA described here highlighted the challenges in appraising interventions with a complex PAS. Based on the analyses that include a discount to the list price of oxaliplatin, the ERG concluded that the ICERs for the addition of bevacizumab to XELOX or FOLFOX were both over £50 000. The NICE Appraisal Committee concluded that bevacizumab in combination with oxaliplatin and either 5-fluorouracil plus folinic acid or capecitabine (i.e. FOLFOX or XELOX) was not recommended for the treatment of mCRC.