Breast cancer (early) - paclitaxel

3. The manufacturer’s submission

The Appraisal Committee (appendix A) considered evidence submitted by the manufacturer of Taxol (Bristol-Myers Squibb) and a review of this submission by the evidence review group (ERG) (appendix B).

3.1. The manufacturer’s submission approached the decision problem by providing evidence about the clinical and cost effectiveness of the regimen, specified in the SPC, of four cycles of the anthracycline doxorubicin and cyclophosphamide (a chemotherapy combination known as AC) followed by four cycles of paclitaxel, compared with four cycles of AC alone. It also provided evidence from comparisons of four cycles of AC followed by four cycles of paclitaxel or docetaxel (another taxane) using regimens that are not currently covered by a marketing authorisation in the UK. The clinical studies included in the manufacturer’s submission were not identified through a systematic review of the relevant literature. In the studies which included four cycles of AC as comparator, the addition of four cycles of paclitaxel after four cycles of AC resulted in statistically significant improvements in disease-free survival (hazard ratio [HR] in both studies 0.83). One of the studies also showed a statistically significant improvement in overall survival (HR 0.82) whereas the other did not.

3.2. The manufacturer’s submission provided economic evidence based on a probabilistic Markov state-transition model that compared four cycles of paclitaxel (following four cycles of AC) with four cycles of AC alone. The reported cost per quality-adjusted life year (QALY) gained for this comparison was £4726.

3.3. The ERG raised a number of issues related to the manufacturer’s submission.

• There was no systematic review of the effectiveness evidence or the cost-effectiveness evidence, or to inform inputs for the economic model.
• The comparator used in the economic analysis (four cycles of AC) is not commonly used in the NHS for the adjuvant treatment of early node-positive breast cancer and is considered less effective than the most commonly used regimens, including extended anthracycline therapy of six to eight cycles.
• No patient subgroups stratified according to prognostic characteristics were considered.
• Utility data were not adjusted for patient age or chemotherapy-specific toxicities.
• The costs of adverse events in the first four cycles with AC were not included in the model, and neutropenia was the only adverse event for which costs were included in the model.

3.4. Full details of all the evidence are in the manufacturer’s submission and the ERG report, which are available from www.nice.org.uk/TA108