3.1 The appraisal committee (section 6) considered evidence submitted by Roche and a review of this submission by the evidence review group. The appraisal was paused in 2014 to allow NICE's decision support unit to provide a discussion paper and then later reconsidered as part of the transition to the new Cancer Drugs Fund system. The reconsideration focussed on the final analysis of the CLEOPATRA trial and an updated economic model that incorporated a confidential commercial access arrangement. See the committee papers for full details of the evidence.
3.2 The company included 1 randomised controlled trial in its original submission (CLEOPATRA). This was a double-blind, randomised, placebo-controlled trial assessing the efficacy and safety of pertuzumab plus trastuzumab and docetaxel in 808 adults with human epidermal growth factor receptor 2 (HER2)‑positive metastatic breast cancer in 25 countries including the UK. Randomisation was stratified by geographic region (Asia, Europe, North America and South America) and prior treatment status (de novo and prior adjuvant or neoadjuvant chemotherapy). Investigators randomised patients in a 1:1 ratio to either pertuzumab plus trastuzumab and docetaxel (n=402), or placebo plus trastuzumab and docetaxel (n=406). Patients had either pertuzumab at a loading dose of 840 mg followed by 420 mg every 3 weeks or by placebo every 3 weeks, until disease progression or unacceptable toxicity occurred. All patients had trastuzumab at a loading dose of 8 mg/kg body weight followed by 6 mg/kg body weight every 3 weeks, and docetaxel 75 to 100 mg/m2 (at investigator discretion) every 3 weeks for at least 6 cycles.