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

• Type of Material: Article
• Authors: Jennifer K. Litton, University of Texas, Houston; Meredith M. Regan, Harvard Medical School; Lajos Pusztai, Yale School of Medicine; Hope S. Rugo, University of California, San Francisco; Sara M. Tolaney, Dana-Farber Cancer Institute; Elizabeth Garrett-Mayer, American Society of Clinical Oncology; Laleh Amiri-Kordestani, US Food and Drug Administration; Reva K. Basho, The Lawrence J. Ellison Institute for Transformative Medicine; Ana F. Best, National Cancer Institute; Jean-Francois Boileau, McGill University; Carsten Denkert, University Marburg; Jared C. Foster, National Cancer Institute; Nadia Harbeck, LMU University Hospital; Heather A. Jacene, Brigham and Women's Hospital; Tari A. King, Brigham and Women's Hospital; Ginny Mason, The Inflammatory Breast Cancer Research Foundation; Ciara C. O'Sullivan, Mayo Clinic, Rochester; Tatiana M. Prowell, Johns Hopkins Kimmel Comprehensive Cancer Center; Andrea L. Richardson, Johns Hopkins Medicine; Karla A. Sepulveda, Baylor College of Medicine; Mary Lou Smith, Research Advocacy Network; Judy A. Tjoe, Novant Health; Gulisa Turashvili, Emory University; Wendy A. Woodward, University of Texas, Houston; Lynn Pearson Butler, The Emmes Corporation; Elena I. Schwartz, National Cancer Institute; Larissa A. Korde, National Cancer Institute
• Language: English
• Date: 2023-07-11
• Publisher: Wolters Kluwer Health, Inc.
• Publication Version: Final Published Version
• Copyright Statement: © 2023 by American Society of Clinical Oncology
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://doi.org/10.1200%2FJCO.23.00435
• Title of Journal or Parent Work: Journal of Clinical Oncology
• Volume: 41
• Issue: 27
• Start Page: 4433
• End Page: 4442
• Keywords: Breast cancer; STEEP
• Research Categories: Health Sciences, 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.