Pertuzumab is a humanised monoclonal antibody that binds HER2 at a different epitope to trastuzumab. Combination treatment with pertuzumab and trastuzumab has shown increased activity and an acceptable safety profile. In the phase III CLEOPATRA study of docetaxel, trastuzumab, and placebo (n= 406) versus docetaxel, trastuzumab, and pertuzumab (n= 402), the primary endpoint of progression-free survival was extended from 12•4 months to 18•5 months with the addition of pertuzumab. In the Lancet Oncology, an interim analysis of overall survival, which was a secondary endpoint in the study, has been reported.
In the intention-to-treat population, 267 patients died by data cutoff (May 14, 2012), 154 (38%) in the placebo group and 113 (28%) in the pertuzumab group. Median overall survival was 37•6 months in the placebo group but had not been reached in the pertuzumab group (hazard ratio 0.66, 95% CI 0•52 to 0•84; p=0•0008). Overall, adverse events were similar to those reported at the primary analysis with respect to frequency, severity, and specificity.
At the time of data cut-off, 68 patients in the placebo group and 104 in the pertuzumab group were alive and on study treatment. Because of the statistically significant effect on survival, crossover to the pertuzumab-containing regimen has been offered to individuals still receiving study treatment in the placebo group. The researchers note that overall, this interim analysis of overall survival accords with findings from the first interim analysis and the primary analysis of independently assessed progression-free survival, an observation that could be attributable to sustained double-blinding of the study and the absence of any crossover before this analysis of overall survival. Of patients receiving subsequent treatment for breast cancer, the types of drugs used were generally balanced between both groups, suggesting that later-line treatment did not affect the overall survival results. Results from exploratory subgroup analyses in general indicate a trend in favour of pertuzumab, but because of the small number of patients and absence of statistical power, interpretation is limited. The final analysis, planned after 385 deaths have been recorded, will be a descriptive follow-up analysis only.
Pertuzumab was recently launched in the UK. NICE is due to appraise its clinical and cost-effectiveness, in combination with trastuzumab and docetaxel within its licensed indication for the treatment of HER2 positive metastatic or locally recurrent unresectable breast cancer, which has not been previously treated, or has relapsed after adjuvant therapy. Guidance is expected in November 2013.