Safety, treatment delivery, and pathological response before and after pembrolizumab implementation for early ER-negative, HER2-normal breast cancer.

BACKGROUND: Pembrolizumab has become standard neoadjuvant systemic therapy (NST) for early estrogen receptor (ER)-negative, human epidermal growth factor receptor 2 (HER2)-normal early breast cancer (eBC). Electronic health record (EHR) data may support real-world assessment of its implementation in routine care. PATIENTS AND METHODS: Using centralized EHR data from eastern Denmark, we identified adults with ER-negative, HER2-normal eBC receiving NST. Patients were grouped by treatment start before (April 2021-June 2022; comparator) or after (April 2023-June 2024; study) pembrolizumab implementation. We compared treatment exposure, adverse events (AEs) from laboratory data, clinical notes, and AE-indicating medications, and pathological complete response (pCR) from pathology records. Follow-up ended 200 days after surgery, progression, or death. Manual validation included 50 patients. RESULTS: Among 210 included patients, 109 were in the study population and 101 in the comparator population. Baseline characteristics were broadly similar. Pembrolizumab was received by 77% versus 0% and carboplatin omission was less frequent after implementation (7% versus 47%). During NST, grade 3/4 AEs were observed in 77 study patients (71%) and 66 comparator patients (65%). Suspected grade 3/4 autoimmune disorders during NST occurred in 18 pembrolizumab-treated study patients (21%) and in no comparator patients, and no grade 5 AEs were identified. pCR was achieved in 74 study patients (68%) versus 49 comparator patients (49%). Manual validation showed high structured-data completeness after resolution of a small number of data processing errors but also identified missing data. CONCLUSION: After introduction of pembrolizumab into NST, patients with early ER-negative, HER2-normal breast cancer (BC) had a higher pCR proportion, alongside a higher toxicity.