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A Retrospective Observational Study of Extended Adjuvant Neratinib for HER2-Positive Early-Stage Breast Cancer in a European Early Access Program

Year: 2025

Type: article

Abstract: 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. 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. Among 108 eligible patients, most had HR+ disease (n = 92) and a high risk of recurrence (defined as stage II–III or node-positive disease, or non-pathological complete response after neoadjuvant therapy; n = 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. These results provide additional data supporting the safety and exploratory effectiveness of neratinib in the EAP, reflecting real-world clinical practice. NCT05599334 (31 October 2022, retrospectively registered). Neratinib is a medication used to treat a type of early-stage breast cancer that is associated with human epidermal growth factor receptor 2 (HER2) proteins on the surface of cancer cells, referred to as ‘HER2-positive’ breast cancer. Neratinib is given by mouth following surgery and subsequent trastuzumab-based treatment. Although the use of neratinib in this way has been investigated in a well-controlled clinical study, more information is needed about the everyday use of neratinib to treat HER2-positive breast cancer within the current treatment landscape. The NEAR study investigated various aspects of neratinib use, including the characteristics of patients treated, duration and effectiveness of neratinib treatment and its safety profile. Data were assessed from 108 adults who had HER2-positive early-stage breast cancer and had been treated with neratinib between 1 August 2017 and 31 December 2020 after having received surgery and trastuzumab. Among these people, most had breast cancer considered to be at high risk of recurring and started neratinib about 5 months after their last dose of trastuzumab. Approximately two thirds of patients reported having a side effect, with diarrhoea being the most common, mostly mild to moderate in severity. Severe diarrhoea could be reduced by taking anti-diarrhoeal medications before the side effect occurred. Patients who received a lower starting dose of neratinib were less likely to have severe diarrhoea and to prematurely stop treatment than those starting at the full recommended dose. Two years after starting treatment with neratinib, 93% of patients remained free of breast cancer.

Source: Oncology and Therapy

DOI: 10.1007/s40487-025-00392-w