Table 4.

Guidelines with recommendations for the use of neratinib in the treatment of early HER2+ breast cancer

Guidelines	Recommendation	Evidence level	Grading of recommendation	Sources
ASCO 2020 American Society of Clinical Oncology	Extended adjuvant therapy with neratinib in patients with HER2-positive early breast cancer Neratinib causes relevant diarrhoea and diarrhoea prophylaxis should be applied	High	Moderate	[16]
ESMO 2019 European Society for Medical Oncology	Extended anti-HER2 therapy with neratinib combined with appropriate diarrhoea prophylaxis and treatment may be considered in selected high-risk patients who have not previously been treated with a double blockade (especially HR+ patients)	I	B	[15, 18]
NCCN 2020 National Comprehensive Cancer Network	Neratinib as a therapy option after adjuvant trastuzumab therapy in HER2+/HR+ Mamma CA with a high risk of recurrence (N+); of note: no data is available for patients who have previously received pertuzumab Neratinib as a therapy option after adjuvant trastuzumab therapy in HER2+/HR+ breast cancer and pCR after neoadjuvant therapy with a high risk of recurrence; of note: no data is available for patients who have previously received pertuzumab or T-DM1	2 A	[17]
AGO	Neratinib combined with standard endocrine therapy after 1 year of adjuvant trastuzumab (HR+)	1b/B	+
Gynaecological
Oncological	Neratinib combined with standard endocrine therapy after 1 year of post-neoadjuvant trastuzumab (HR+, non-pCR) Primary prophylaxis with loperamide	3b/B	+/−	[8, 55]
Working Group e.V.		2b/B	++

HER2, human epidermal growth factor receptor 2; HR, hormone receptor; Mamma CA, breast cancer; N, lymph node/nodal status; pCR, pathological complete response; T-DM1, trastuzumab-emtansine.