Real-World Data Backs Invasive DFS as Surrogate Endpoint for OS in EBC

Invasive disease-free survival (iDFS) is a reliable surrogate endpoint for overall survival (OS) in trials of hormone receptor-positive/HER2-negative early breast cancer, according to a real-world study published in Cancer.

“Although OS is the ‘gold standard’ endpoint in clinical trials, a challenge is the extended follow-up periods needed to detect sufficient events for adequately powered analysis,” wrote study researchers led by Stephanie L. Graff, MD, of Legorreta Cancer Center at Brown University, Providence, Rhode Island. “This may limit the use of OS as the primary endpoint in some oncology trials. This limitation is particularly relevant in breast cancer, where standard-of-care targeted therapies have improved outcomes in metastatic disease, making it even more challenging to demonstrate OS benefit in early breast cancer.”

In contrast, evaluation of iDFS requires shorter follow-up times. Dr. Graff and colleagues conducted a retrospective analysis of patient data to assess if iDFS could be used as a surrogate endpoint for OS in adjuvant HR-positive/HER2-negative early breast cancer. Included data was from 3,133 patients aged 18 or older with stage II or III disease; patients had prior surgery and adjuvant endocrine therapy.

The median follow-up time was about 4.5 years. Among the included patients, about one-third (35.2%) had iDFS events; 17.7% had an OS event.

In the overall patient cohort, iDFS and OS had “a positive, very strong, clinically relevant correlation.” There was a positive correlation between iDFS and OS (Spearman coefficient ρ = 0.88; 95% CI, 0.87-0.89; P< .0001). iDFS accounted for 82% of the variation in OS.

Similar correlations were seen for subgroups of patients including analysis by endocrine therapy, menopausal status, disease stage, nodal involvement, and prior therapy. All these groups had a “very strong” correlation except stage III disease, which had a “strong” correlation.

“Our study adds to the body of knowledge showing that iDFS is a clinically relevant surrogate for OS, as it showed there was a very strong correlation in all categories that were tested, including varying ET treatment,” the study researchers wrote. “This suggests that the use of iDFS in clinical trials is justifiable.”

Reference

Graff SL, Tolaney SM, Hart LL, et al. Correlation analysis of invasive disease-free survival and overall survival in a real-world population of patients with HR+/HER2– early breast cancer. Cancer. 2025;e35817. doi:10.1002/cncr.35817