Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Division of Biostatistics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
J Clin Oncol. 2023 Sep 20;41(27):4433-4442. doi: 10.1200/JCO.23.00435. Epub 2023 Jul 11.
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.
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.
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.
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.
标准化疗效终点定义（STEEP）标准于 2007 年建立，并于 2021 年更新（STEEP 2.0），为辅助乳腺癌（BC）终点提供了标准化定义。STEEP 2.0 确定需要分别解决新辅助临床试验的终点问题。为此，成立了多学科新辅助 STEEP 工作组，专门负责评估和调整新辅助 BC 试验终点。
新辅助 STEEP 工作组主要关注具有疗效结果的新辅助系统治疗临床试验的终点，包括病理和时间相关生存终点，特别是基于注册目的的终点。还考虑了亚组和治疗方法、影像学、手术时的淋巴结分期、双侧和多灶性疾病、相关组织采集以及美国食品和药物管理局（FDA）监管考虑因素。
工作组建议将病理完全缓解（pCR）的首选定义为完整切除的乳腺标本和所有取样的区域淋巴结中不存在残留浸润性癌（根据 AJCC 分期为 ypT0/Tis ypN0）。残留癌负荷应作为次要终点，以促进未来对其效用的评估。激素受体阳性疾病需要替代终点。时间相关生存终点的定义应特别注意测量起点。试验应包括从随机分组开始的终点（无事件生存和总生存），以捕获术前进展和死亡事件。也可以使用从根治性手术开始定义的来自 STEEP 2.0 的次要终点。规范和标准化活检方案、影像学和病理淋巴结评估也至关重要。
除了 pCR 之外，还应根据肿瘤的临床和生物学特征以及所研究的治疗药物选择终点。一致的预设定义和干预措施对于有临床意义的试验结果和跨试验比较至关重要。
