Introduction <p>Neratinib is approved in Europe as extended adjuvant therapy in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-positive (HER2+) early-stage breast cancer (EBC) who completed adjuvant trastuzumab-based therapy within 1 year. Real-world data are necessary to define the role of neratinib in the evolving treatment landscape.</p> Methods <p>NEAR was a retrospective, observational study evaluating treatment patterns, safety and effectiveness of neratinib during a European early access program (EAP). Eligible patients had HER2+ EBC and received neratinib between August 2017 and December 2020. Data were extracted from medical records up to July 2022. The primary endpoint was the patient demographic and clinical profile.</p> Results <p>Among 108&#xa0;eligible patients, most had HR+ disease (<i>n</i> = 92) and a high risk of recurrence (defined as stage II–III or node-positive disease, or non-pathological complete response after neoadjuvant therapy; <i>n</i> = 87); 74 were treated as per the neratinib European label. Trastuzumab plus pertuzumab and trastuzumab alone were the most common anti-HER2+ adjuvant therapies (9.3% and 88.4% of patients, respectively). Median duration of neratinib treatment was 12.3 months. Diarrhoea was the most common adverse event (58.3%). Prophylactic anti-diarrhoeal therapy reduced the occurrence of grade ≥ 3 diarrhoea (4.3% versus 13.2% without prophylaxis) and neratinib discontinuation (22.2% versus 35.7%, respectively). Exploratory invasive disease-free survival rates were 93.3% at 24 months and 89.9% at 36 months, with no central nervous system events.</p> Conclusion <p>These results provide additional data supporting the safety and exploratory effectiveness of neratinib in the EAP, reflecting real-world clinical practice.</p> ClinicalTrials.gov Identifier <p>NCT05599334 (31 October 2022, retrospectively registered).</p>