Three year data have been required

Three year data have been required in general in the setting of adjuvant treatment of breast cancer. The robustness of the data for the 2 year is acknolewdged, but due to the study conduct after the 2 year phase (see above), the extent of benefit at five years remains uncertain; however, maintained benefit is expected, especially in the restricted HRc+ population with a larger effect size. The limited tolerability of Nerlynx due to diarrhoea, frequently leading to treatment discontinuation, is recognized as an important limitation on clinical utility. However, this side effect is reversible on discontinuation and further studies to identify appropriate strategies for anti-diarrhoeal management are underway (see RMP). Furthermore, no safety issues of major concern to negate the demonstrated benefit have emerged. At present, from a patient and clinical perspective, as long as benefits, risks, and uncertainties are clearly understood, it is considered that meaningful treatment decisions can be made and that treatment with neratinib can be a good option for some patients. Consequently, while it is recognized that adjuvant treatment with Nerlynx may not be appropriate for every patient, it is considered a reasonable treatment option on a case by case basis, as extended adjuvant therapy for HER2+, HRc+ early breast cancer (see PI). The clinical utility is expected to improve with optimisation of anti-diarrhoeal management.