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

<h3>Background</h3> 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. <h3>Materials and methods</h3> 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 <i>in situ</i> disease) and rwEFS (time from NAC start to first event). Outcomes were compared with those from the KEYNOTE-522 control arm. <h3>Results</h3> In the RW cohort (<i>n</i> = 128), rwpCR was 37.5%, compared with 51.2% pCR in the KEYNOTE-522 control arm (<i>n</i> = 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 <i>P</i> = 0.97). The incidence rates of first events were also similar (22.0% RW versus 23.8% trial). <h3>Conclusions</h3> 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.