Abstract PO1-01-06: Patterns in use and tolerance of adjuvant neratinib in patients with hormone receptor (HR)-positive, HER2-positive early-stage breast cancer
Authors: Blanter Julia , Baldwin Elena , Patel Rima , Sheng Tianxiang , Tiersten Amy 
Published: May 2024

Abstract
Background: In the ExteNET study, 1 year of neratinib therapy was shown to derive a significant invasive disease-free survival (iDFS) benefit in HR+, HER2+, node-positive disease after trastuzumab-based adjuvant therapy. Currently, the NCCN guidelines recommend extended adjuvant neratinib following trastuzumab-based therapy for patients (pts) with high-risk HR+ HER2+ disease. Limitations to use of neratinib include significant gastrointestinal side effects which often result in pts discontinuing treatment. In this study, we aimed to identify high-risk clinical features and characteristics of pts who were offered adjuvant neratinib therapy and factors that impacted treatment completion versus discontinuation. Methods: We performed a retrospective review of all pts with early-stage HR+ HER2+ breast cancer who were prescribed neratinib from 2017-2023 at our institution. We used the electronic medical record to extract information on patient characteristics, clinical and high-risk features. High-risk was defined as any of the following: at least 4 lymph nodes positive for disease, 1-3 lymph nodes positive for disease and a grade 3 (poorly differentiated) tumor, tumor &gt; 5 cm, or Ki67 &gt; 20%. Length of time on treatment, treatment holds, dose reductions and up-titrations were documented. Statistical analysis was performed using two-sided T-tests and chi-square tests. Results: We identified 62 eligible pts of whom 34 (55%) completed 1 year of neratinib and 28 (45%) did not. Median age at diagnosis was 51.5 years. 49% of pts were pre-menopausal at diagnosis, 43% were post-menopausal, 5% were peri-menopausal and 3% had undocumented menopausal status at diagnosis. Clinical features of the pts are documented in Table 1. Sixty percent of patients offered neratinib were considered high-risk at diagnosis, based on definitions described above. 73% of pts received neoadjuvant treatment with pertuzumab in addition to trastuzumab. 24 pts (39%) had residual disease and 22 pts (35%) received adjuvant T-DM1. The most common reason for neratinib discontinuation was inability to tolerate side effects (54%) followed by pill burden (18%). The most common side effect experienced by pts was diarrhea despite anti-diarrheal prophylaxis (56%), followed by rash (8%). Pts who received an up-titration of neratinib were more likely to complete the full course of neratinib when compared to those who did not (76% vs. 40.5% p = 0.013). The median starting dose of those who completed neratinib treatment was 140 mg vs. 240 mg in those who did not (p = 0.016). The median length of time on neratinib for those that did not complete the 1-year treatment course was 30 days. Neither group experienced a statistically significant greater likelihood of treatment holds or dose reductions. In terms of outcomes, 10 pts had progression of disease of whom 7 did not complete neratinib treatment (p = 0.169). Interestingly, those 7 pts developed metastatic disease and 57% had central nervous system metastases. Conclusions: Pts are more likely to complete 1 year of adjuvant neratinib with dose up-titration. Dose reductions and interruptions did not affect neratinib adherence in our patient population. Seven pts in our study developed metastatic disease, all of whom did not complete adjuvant neratinib treatment. Future prospective studies are needed to further determine the impact of adjuvant neratinib treatment on iDFS in pts who have received pertuzumab and/or T-DM1.
Table 1: Clinical Features of Patients Prescribed Neratinib
Citation Format: Julia Blanter, Elena Baldwin, Rima Patel, Tianxiang Sheng, Amy Tiersten. Patterns in use and tolerance of adjuvant neratinib in patients with hormone receptor (HR)-positive, HER2-positive early-stage breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-01-06.