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

利用美国二级数据库,制定和评估早期三阴性乳腺癌患者真实世界临床终点的定义

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Abstract

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.

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