Real-world evidence (RWE) of effectiveness and safety of TCHP regimen: INSIGHT-HER2BC trial interim results

BackgroundTrastuzumab-based neoadjuvant therapy (NAT) is a standard of care for localized HER2-positive breast cancer (HER2+ BC). TCHP regimen has proven efficacy and safety by TRYPHAENA and KRISTINE trial results. However, the data from RWE trials are quite limited. Here we report the data of the continuing ambispective observational RWE program to assess the efficacy and safety of the TCHP regimen in pts with HER2+ BC – INSIGHT trial.MethodsThis ongoing ambispective study included 1154 pts with HER2+ BC who underwent ≥1 cycle of NAT TCHP at three Moscow oncology centers since Jan’2017 to data cut-off at Jan’2024. We performed statistical analysis (Chi-Square test, survival rates, log-rank test) of various clinical features to assess the effectiveness and safety of treatment.ResultsThe median age of pts was 56.0 years (range: 23-85). 71.3% of them has hormone-positive (HER2+HR+) tumor and 28.7% - hormone-negative (HER2+HR-). Mastectomy was performed in 85.6% (n=988) pts and resection in 14.4% (n=166) pts. The data about the morphological response was available for 1053 pts. pCR was achieved in 60.3% pts (n=696) (pCR+), 75.1% in HER2+HR- subgroup in comparison with 54.3% for HER2+HR+ pts, p<0.05. At the data cut-off, the median follow-up was 28.0 months. 5y-DFS rate was higher in pts received complete NAT (6 cycles) vs. incomplete (<6 cycles): 99.2% vs. 96.1% (p<0.05) and in pCR+ group compared to pCR-: 97% vs. 95% (p<0.05). 5y-DFS rate difference was not statistically significant in HER2+HR+ vs. HER2+HR- pts. Grade 3-4 adverse events (AEs) were reported in 12.7%: neutropenia was the most frequent (60%), and the others were anemia, diarrhea, atrial fibrillation, hypertension, and esophagitis.ConclusionsWe consider TCHP as the effective regimen in a real-world population of HER2+ BC patients. Our results are comparable with TRYPHAENA and KRISTINE trials but the safety profile were different with lower occurrence of grade 3-4 AEs in real-world scenarios. Our study is limited to imbalanced and suboptimal data input which we aim to fix as the project is ongoing. It also highlights the importance of data quality control in routine electronic medical records management to effectively utilize RWE-based data.Legal entity responsible for the studyMoscow City Healthcare Department.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.