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

Authors

Jennifer K Litton
Meredith M Regan
Lajos Pusztai
Hope S Rugo
Sara M Tolaney
Elizabeth Garrett-Mayer
Laleh Amiri-Kordestani
Reva K Basho
Ana F Best
Jean-Francois Boileau
Carsten Denkert
Jared C Foster
Nadia Harbeck
Heather A Jacene
Tari A King
Ginny Mason
Ciara C O'Sullivan
Tatiana M Prowell
Andrea L Richardson
Karla A Sepulveda
Mary Lou Smith
Judy A Tjoe
Gulisa Turashvili
Wendy A Woodward
Lynn Pearson Butler
Elena I Schwartz
Larissa A Korde

Publication Date

9-20-2023

Journal

Journal of Clinical Oncology

Abstract

PURPOSE: The Standardized Definitions for Efficacy End Points (STEEP) criteria, established in 2007 and updated in 2021 (STEEP 2.0), provide standardized definitions of adjuvant breast cancer (BC) end points. STEEP 2.0 identified a need to separately address end points for neoadjuvant clinical trials. The multidisciplinary NeoSTEEP working group of experts was convened to critically evaluate and align neoadjuvant BC trial end points.

METHODS: The NeoSTEEP working group concentrated on neoadjuvant systemic therapy end points in clinical trials with efficacy outcomes-both pathologic and time-to-event survival end points-particularly for registrational intent. Special considerations for subtypes and therapeutic approaches, imaging, nodal staging at surgery, bilateral and multifocal diseases, correlative tissue collection, and US Food and Drug Administration regulatory considerations were contemplated.

RESULTS: The working group recommends a preferred definition of pathologic complete response (pCR) as the absence of residual invasive cancer in the complete resected breast specimen and all sampled regional lymph nodes (ypT0/Tis ypN0 per AJCC staging). Residual cancer burden should be a secondary end point to facilitate future assessment of its utility. Alternative end points are needed for hormone receptor-positive disease. Time-to-event survival end point definitions should pay particular attention to the measurement starting point. Trials should include end points originating at random assignment (event-free survival and overall survival) to capture presurgery progression and deaths as events. Secondary end points adapted from STEEP 2.0, which are defined from starting at curative-intent surgery, may also be appropriate. Specification and standardization of biopsy protocols, imaging, and pathologic nodal evaluation are also crucial.

CONCLUSION: End points in addition to pCR should be selected on the basis of clinical and biologic aspects of the tumor and the therapeutic agent investigated. Consistent prespecified definitions and interventions are paramount for clinically meaningful trial results and cross-trial comparison.

Keywords

Humans, Female, Breast Neoplasms, Neoadjuvant Therapy, Research Design, Progression-Free Survival

Comments

PMID: 37433103