Position Paper on the Value of Extended Adjuvant Therapy with Neratinib for Early HER2+/HR+ Breast Cancer.

backgroundIn August 2018, neratinib - an oral, irreversible pan-HER-tyrosine-kinase inhibitor - was approved by the European Commission for the extended adjuvant treatment of adult patients with early-stage, hormone receptor-positive (HR+), HER2 overexpressed/amplified (HER2+) breast cancer who completed trastuzumab-based adjuvant therapy within the last year. Despite recent improvements in long-term outcome, there is still an unmet need to further reduce the risk of recurrence, especially in patients with poor response to neoadjuvant treatment. SUMMARY: National and international guidelines included recommendations for using neratinib. Based on the health technology assessment for neratinib, the Federal Joint Committee (G-BA) in Germany has granted an added benefit for neratinib compared with the standard "watch and wait" strategies. Inclusion in the Reimbursement Code, however, was rejected by the Austrian social insurance companies in July 2020, and neratinib is now in the "No Box" for individual head physician reimbursement. KEY MESSAGES: We analysed the value of extended adjuvant therapy with neratinib in early HER2+/HR+ breast cancer based on current data and made recommendations for the evidence-based and economical use of neratinib in Austria. In particular, prognostic factors associated with an increased risk of recurrence following standard therapy are considered. Extended adjuvant therapy should be offered primarily to nodal-positive patients at surgery. For nodal-negative patients, neratinib therapy may be considered in case of large and/or inflammatory primary tumours (T3-4) without pathological complete response after neoadjuvant therapy. For all other patients, neratinib may be considered depending on additional risk factors on an individual basis that should be evaluated by interdisciplinary tumour conferences.