Ethnic disparities in pathological complete response and immune-related adverse events with neoadjuvant pembrolizumab in early triple-negative breast cancer

Abstract

Background: Pembrolizumab, combined with chemotherapy, is the standard-of-care neoadjuvant treatment for early triple-negative breast cancer (eTNBC). While there is growing real-world data on pembrolizumab-induced immune-related adverse events (irAEs) and rates of pathological complete response (pCR), little is known about how these outcomes vary across different ethnic groups. At St. Bartholomew's Hospital, which serves a highly diverse patient population, we investigated the impact of ethnicity on treatment outcomes and toxicity profiles. Method(s): We conducted a retrospective review of electronic medical records for 96 patients with eTNBC who received pembrolizumab and chemotherapy between December 2022 and August 2024. Treatment outcomes and irAEs were analyzed and compared with data from the KEYNOTE-522 trial. Result(s): The patient cohort included individuals who self-identified as White (39.4%), Asian (33.0%), Black (12.8%), Other (9.6%), Mixed (2.1%), and Not Stated (3.2%). Among the 96 patients, 50 presented with T2N0 staging. Immune-related adverse events were reported in 50% of patients, with significant variability across ethnic groups. Asian patients had the highest prevalence at 64.5%, followed by White patients at 49.9%, and Black patients at 33.3%. Notably, grade 3 ALT elevation was observed in 10% of our cohort, compared to 5% in the KEYNOTE-522 study, with 18.4% of Asian patients experiencing this irAE. Pathological complete response (pCR) data was available for 85 patients, with an overall pCR rate of 50.6%, lower than the 64.8% reported in the KEYNOTE-522 trial. pCR rates in the White and Black patients were higher at 53% and 55% respectively, whereas the rate in the Asian subgroup was lower at 47%. Our patient cohort was more diverse than that of the KEYNOTE-522 trial, which may have contributed to our lower overall pCR rate. Conclusion(s): This study reveals significant ethnic disparities in pCR and irAEs following treatment with neoadjuvant pembrolizumab, highlighting the need for further research into ethnicity-specific responses, greater clinician awareness, and improved patient education on irAEs. Legal entity responsible for the study: St. Bartholomew's Hospital. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest. Copyright © 2025