Abstract P3-10-12: Retrospective analysis of adverse events and outcomes of patients receiving neoadjuvant pembrolizumab for triple negative breast cancer in Australia

Field: Medicine (Health Sciences)

Abstract Introduction and objectives: Neoadjuvant pembrolizumab combined with chemotherapy has become the standard of care since 2022, for patients with triple negative breast cancer (TNBC) in Australia, following the KEYNOTE-522 trial, which identified significantly higher pathological complete response (pCR) compared to placebo, acknowledging the serious immune-related adverse events (irAEs) (1). A secondary analysis of this trial included patients enrolled in Asia and found similar rates of grade 3-4 irAEs in the pembrolizumab and placebo groups (3). Reports of adverse outcomes are often overshadowed by the significant benefit of pembrolizumab in TNBC, a subtype of breast cancer with significant risk of recurrence and mortality (2). Our objective was to collect real-world data relating to the use of neoadjuvant pembrolizumab in patients with TNBC, to identify the pattern of adverse events and outcomes. Methods: Retrospective data was collected across three tertiary hospitals in Melbourne, Australia, for patients diagnosed with TNBC, who received neoadjuvant pembrolizumab; baseline demographics, medical background, primary tumour details, pembrolizumab and chemotherapy regimen, serious adverse events and their management, breast surgery and pathological response. Results: There were 54 female patients who received neoadjuvant pembrolizumab; median age 52 years and median follow up of 11 months. 4 patients had a history of autoimmune disease and 2 had immunosuppressant therapy during or within 2 years prior to treatment with pembrolizumab. At primary diagnosis, 69% had nodal involvement. At least one irAE occurred in 54% of patients; thyroiditis (22%), adrenal insufficiency (20%), colitis (7%), hepatitis (6%) rash of at least grade 3 severity (4%) and pneumonitis (4%). Other less frequent irAEs include autoimmune haemolytic anaemia, transverse myelitis, arthralgia and type 1 diabetes mellitus. Of those with irAEs, 45% were hospitalised, 1 patient required intensive care and 69% have ongoing sequelae. The median time from commencement of pembrolizumab to irAE onset was 84 days. An interruption in pembrolizumab dose occurred in 23 patients, with 70% of these discontinuing therapy early. 41 patients underwent surgical intervention, and 40 had lymph node dissection. pCR was achieved in 37%, while 60% of those who achieved pCR experienced at least one irAE. Conclusion: There are significant immune related adverse events associated with the use of neoadjuvant pembrolizumab, a notable proportion of whom required hospitalisation, which poses an important and concerning burden for patients and the healthcare system. These real-world outcomes will continue to be monitored. Further work should also look at survival outcomes and quality of life, to better inform shared-decision making. References: Schmid, P. et al. (2020) ‘Pembrolizumab for early triple-negative breast cancer’, New England Journal of Medicine, 382(9), pp. 810–821. doi:10.1056/nejmoa1910549. Hudis, C.A. and Gianni, L. (2011) ‘Triple-negative breast cancer: An unmet medical need’, The Oncologist, 16(S1), pp. 1–11. doi:10.1634/theoncologist.2011-s1-01. Takahashi, M. et al. (2023) ‘Pembrolizumab plus chemotherapy followed by pembrolizumab in patients with early triple-negative breast cancer’, JAMA Network Open, 6(11). doi:10.1001/jamanetworkopen.2023.42107. Citation Format: Evon Jude, Jasmine Grisold, Sarah Jaboury, Qing Ze Fang, Josephine Stewart, Frances Barnett, Bianca Devitt, Belinda Yeo. Retrospective analysis of adverse events and outcomes of patients receiving neoadjuvant pembrolizumab for triple negative breast cancer in Australia [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-10-12.