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

<b><i>Background:</i></b> In 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. <b><i>Summary:</i></b> 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. <b><i>Key Messages:</i></b> 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.

The Neat-HER virtual registry: Updated results on HER2+ breast cancer patients receiving neratinib as extended adjuvant therapy.

e13565 Background: Data from traditional registries are usually limited to patients treated at study sites. Virtual registries can enroll a broader real-world population. Neat-HER is a U.S.-based virtual registry pilot through PicnicHealth that is enrolling patients with HER2+ breast cancer receiving neratinib as extended adjuvant therapy. Methods: Neat-HER evaluates the feasibility of enrolling patients and answering research questions using a novel electronic platform. Eligibility includes receipt of neratinib in the extended adjuvant setting, signed informed consent for medical record retrieval/data abstraction and age > 18 years. Patients who do not complete enrollment procedures, are participating in a clinical trial or have metastatic disease are excluded. Patients are recruited through multiple mechanisms including private social media groups, treating clinicians and patients enrolled in the Puma Texting Program. Patient health records for breast cancer-related treatment are collected from time of diagnosis to 1-year post-enrollment in the registry. Research questions focus on patient and tumor characteristics, receipt of therapy (e.g. radiotherapy, adjuvant therapy), neratinib duration, and diarrhea prophylaxis. Results: 33 patients with HER2+ early-stage breast cancer who received neratinib as extended adjuvant therapy have been enrolled in this registry study since December 2018. Median age was 50 years, with 79% of patients self-identifying as white. 82% of patients had hormone receptor-positive (ER/PR) disease and 73% of patients had node-positive disease. Prior HER2-targeted adjuvant therapy regimens were as follows: trastuzumab with paclitaxel (9%); trastuzumab/pertuzumab in combination with a taxane(s) (91%). 17 patients (52%) completed 12 months of neratinib treatment; 4 patients (12%) discontinued treatment early; 10 patients (30%) were still ongoing at the time of data cutoff. 31 patients (94%) had diarrhea prophylaxis discussed prior to the start of neratinib treatment. Conclusions: Neat-HER provides useful information on patient/tumor characteristics and treatment patterns in a real-world cohort receiving extended adjuvant neratinib and patient recruitment is ongoing. Updated results show that this pilot virtual registry continues to be a feasible and efficient modality to collect important data on descriptive characteristics and treatment patterns for a patient population derived from real-world practice settings. Validation of this method is needed and could be used in other tumor types.