Developing and evaluating definitions of real-world clinical endpoints for patients with early-stage triple-negative breast cancer using a United States of America secondary database

Background The KEYNOTE-522 trial showed that neoadjuvant chemotherapy (NAC) plus adjuvant pembrolizumab improved overall survival, event-free survival (EFS), and pathological complete response (pCR) in high-risk early-stage triple-negative breast cancer. As treatments evolve, evaluating real-world (RW) effectiveness is key to understanding trial generalizability. This study benchmarked RW efficacy endpoints in early-stage triple-negative breast cancer patients treated with NAC. Materials and methods This retrospective study used RW data from United States community practices abstracted by oncology data specialists. Eligible patients received NAC regimens similar to the KEYNOTE-522 control arm. Control arm patients received no adjuvant therapy, while the RW cohort could receive adjuvant capecitabine. Two RW endpoints were assessed: rwpCR (ypT0/Tis ypN0 or clinical pCR with in situ disease) and rwEFS (time from NAC start to first event). Outcomes were compared with those from the KEYNOTE-522 control arm. Results In the RW cohort (n = 128), rwpCR was 37.5%, compared with 51.2% pCR in the KEYNOTE-522 control arm (n = 390). rwEFS over 36 months was comparable: 75.0% (95% confidence interval 67.1% to 83.8%) in the RW cohort versus 76.8% (95% confidence interval 72.2% to 80.7%) in the KEYNOTE-522 control arm (log-rank P = 0.97). The incidence rates of first events were also similar (22.0% RW versus 23.8% trial). Conclusions Although pCR rates were higher in the KEYNOTE-522 control arm compared with the RW cohort, rwEFS was comparable with EFS in the KEYNOTE-522 control arm. This study highlights the value of combining structured data with custom abstraction to assess RW endpoints and support future research.