Authors' objectives:

The objective of the appraisal was to evaluate the clinical effectiveness and cost-effectiveness of bevacizumab, within its licensed indications, in combination with oxaliplatin and either 5-fluorouracil or capecitabine for the treatment of metastatic colorectal cancer. The comparator was oxaliplatin or irinotecan, including chemotherapy regimens without bevacizumab. Measured outcomes included overall survival, progression-free survival, response rate, adverse effects of treatment and health-related quality of life.

Authors' recommendations: The NO16966 trial was of reasonable methodological quality and demonstrated a significant improvement in both progression-free survival and overall survival when bevacizumab wasadded to XELOX or FOLFOX. However, the size of the actual treatment effect of bevacizumab is uncertain due to the following:Trial design limitations (two-part study, open-label design)Imbalance of known prognostic factor (time between primary treatment and recurrence) Relatively short duration of chemotherapy treatment (approximately 6 months) despite the fact that the trial protocol allowed continuation of the study therapy until progressive disease or unacceptable toxicityInterpretation of the statistical analyses (pooled analysis of all patients versus analysis by factorial design). In addition, there was uncertainty around whether bevacizumab treatment should be continued until progression of the underlying disease. The ERG believed that the modelling structure employed was appropriate, but highlighted several key issues and areas of uncertainty and included the following:It is unclear which approach to data analysis (pooling, excluding adjuvant therapy patients, etc.) is most appropriate and the choice of approach has a significant impact on theresulting ICERs.Unlike the N016966 trial, in clinical practice chemotherapy may be administered intermittently rather than continuously. This introduces considerable uncertainty as the differences in cost and efficacy between intermittent and continuous use are not known.At the time of writing the decision on whether the proposed PAS scheme would be accepted was unknown. The majority of the analysis presented by the manufacturer included thePAS. Running the model without the PAS resulted in much higher ICERs.The efficacy associated with the continuation of treatment with bevacizumab after cessation of oxaliplatin is unknown. However, with the PAS the incremental cost of continuing bevacizumab after oxaliplatin cessation is almost three times the incremental cost of adding bevacizumab to oxaliplatin. Hence bevacizumab treatment post oxaliplatin cessation has the potential to have a significant impact on the resulting ICERs.

Project Status: Completed

URL for project: http://www.hta.ac.uk/erg/supplements/supplement1402.pdf#nameddest=article07

Year Published: 2010

URL for published report: http://www.hta.ac.uk/project/2059.asp

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: England, United Kingdom

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk

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