Developing and Evaluating Definitions of Real-World (rw) Clinical Endpoints for Patients with Early-Stage Triple Negative Breast Cancer (esTNBC) Using a US Secondary Database
Author(s)
Xiaohan Hu, MPH, PhD1, Amin Haiderali, MBA, MPH1, Jagadeswara Rao Earla, MBA, PharmD, PhD1, Giovanna I. Cruz, PhD, MS2, Hina Mohammed, MPH2, Tara Privette, BS2, Ronda Broome, MS, MSHMI2, Arelis Hernandez, MPH2, Radha Krishnan, MD1, Wilbur Pan, MD, PhD1;
1Merck & Co., Inc., Rahway, NJ, USA, 2Syapse Holdings Inc., West Chester, PA, USA
1Merck & Co., Inc., Rahway, NJ, USA, 2Syapse Holdings Inc., West Chester, PA, USA
Presentation Documents
OBJECTIVES: Real-world databases comprising electronic medical records can serve as rich sources of rw clinical information to evaluate treatment effectiveness in oncology. This retrospective study aimed to develop and evaluate rw early clinical endpoints for patients with esTNBC receiving care in the US.
METHODS: A rw-cohort was selected from the Syapse Learning Health Network of US community health systems including patients with esTNBC first diagnosed from 1-Jan-2016 to 31-Dec-2021 and ECOG performance status of 0-1 (or unknown). Eligible patients underwent surgery at the primary site after neoadjuvant therapy (NAT) regimens similar to those for the control arm of the KEYNOTE-522 trial (NCT03036488) with previously untreated stage II/III TNBC who received NAT+placebo, followed by definitive surgery. Patients enrolled in a clinical trial or who had prior immune checkpoint inhibitor therapy were excluded. We contrasted endpoint distribution with that for the KEYNOTE-522 control arm, including rw-pathologic complete response by local pathology assessment (rwpCR: no residual invasive cancer in resected tissue [ypT0/Tis ypN0]) and rw-event-free survival (rwEFS) estimated by Kaplan-Meier from NACT initiation. The rw-cohort was followed through 31-Dec-2023.
RESULTS: In the rw-cohort (n=128)/KEYNOTE-522 control arm (n=390), median ages were 54/48 years; 62%/43% of women were postmenopausal; 24%/13% had ECOG PS of 1; 34%/26% had tumor size T3-T4; 55%/25% had clinical stage III TNBC. Median follow-up times were 31.2/39.1 months. The rwpCR rate was 38%; the KEYNOTE-522 control arm pCR was 51%. Medians for rwEFS/EFS were not reached; the 36-month rwEFS/EFS rates were 75.0% (95% CI, 67.1-83.8) and 76.8% (72.2-80.7).
CONCLUSIONS: For patients with esTNBC, the rwpCR tended to be lower than the pCR in the trial control arm, while rwEFS/EFS results were similar. Differences in patient characteristics and in dosage and duration of the neoadjuvant treatment regimens might have contributed to the differences between rw and trial settings.
METHODS: A rw-cohort was selected from the Syapse Learning Health Network of US community health systems including patients with esTNBC first diagnosed from 1-Jan-2016 to 31-Dec-2021 and ECOG performance status of 0-1 (or unknown). Eligible patients underwent surgery at the primary site after neoadjuvant therapy (NAT) regimens similar to those for the control arm of the KEYNOTE-522 trial (NCT03036488) with previously untreated stage II/III TNBC who received NAT+placebo, followed by definitive surgery. Patients enrolled in a clinical trial or who had prior immune checkpoint inhibitor therapy were excluded. We contrasted endpoint distribution with that for the KEYNOTE-522 control arm, including rw-pathologic complete response by local pathology assessment (rwpCR: no residual invasive cancer in resected tissue [ypT0/Tis ypN0]) and rw-event-free survival (rwEFS) estimated by Kaplan-Meier from NACT initiation. The rw-cohort was followed through 31-Dec-2023.
RESULTS: In the rw-cohort (n=128)/KEYNOTE-522 control arm (n=390), median ages were 54/48 years; 62%/43% of women were postmenopausal; 24%/13% had ECOG PS of 1; 34%/26% had tumor size T3-T4; 55%/25% had clinical stage III TNBC. Median follow-up times were 31.2/39.1 months. The rwpCR rate was 38%; the KEYNOTE-522 control arm pCR was 51%. Medians for rwEFS/EFS were not reached; the 36-month rwEFS/EFS rates were 75.0% (95% CI, 67.1-83.8) and 76.8% (72.2-80.7).
CONCLUSIONS: For patients with esTNBC, the rwpCR tended to be lower than the pCR in the trial control arm, while rwEFS/EFS results were similar. Differences in patient characteristics and in dosage and duration of the neoadjuvant treatment regimens might have contributed to the differences between rw and trial settings.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
CO161
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment
Disease
SDC: Oncology