• Although the single pivotal trial

• Although the single pivotal trial submitted in support of the application achieves nominal statistical significance, it falls short of the expectations to be exceptionally compelling and with precise estimates of the treatment effect as described in the points to consider document on applications with one pivotal study (CPMP/EWP/2330/99). For the primary endpoint of invasive disease-free survival (iDFS) in the intention-to-treat population, the 2-year and 5-year point estimates for hazard ratio (0.66-0.73) and absolute difference (2.3-2.5%) are modest in absolute terms in particular if maintained in the long term. However, the effect size is uncertain due to incomplete re-consent for longer term follow-up, and hence the potential for important bias in the estimated treatment effect.