Standardized Definitions for Efficacy End Points in Neoadjuvant Breast Cancer Clinical Trials: NeoSTEEP.

Area of Science:

• Oncology
• Clinical Trials
• Biostatistics

Background:

• The Standardized Definitions for Efficacy End Points (STEEP) criteria, updated in 2021, established definitions for adjuvant breast cancer (BC) end points.
• STEEP 2.0 highlighted the need for distinct end points in neoadjuvant BC clinical trials.

Purpose of the Study:

• To critically evaluate and align end points for neoadjuvant breast cancer clinical trials.
• To develop standardized definitions for efficacy outcomes in neoadjuvant systemic therapy trials.

Main Methods:

• A multidisciplinary NeoSTEEP working group of experts was convened.
• Focused on neoadjuvant systemic therapy end points, including pathologic and time-to-event survival outcomes.
• Considered subtype-specific needs, imaging, nodal staging, and regulatory factors.

Main Results:

• Recommends defining pathologic complete response (pCR) as absence of residual invasive cancer in breast and lymph nodes (ypT0/Tis ypN0).
• Suggests residual cancer burden as a secondary end point and calls for alternative end points for hormone receptor-positive disease.
• Advocates for time-to-event end points measured from random assignment (event-free survival, overall survival) to capture early events.

Conclusions:

• End point selection should align with tumor biology and therapeutic agents.
• Consistent, prespecified definitions and interventions are crucial for meaningful trial results and cross-trial comparisons.