Updated Standardized Definitions for Efficacy End Points (STEEP) in Adjuvant Breast Cancer Clinical Trials: STEEP Version 2.0

Abstract

PURPOSE The Standardized Definitions for Efficacy End Points (STEEP) criteria, established in 2007, provide standardized definitions of adjuvant breast cancer clinical trial end points. Given the evolution of breast cancer clinical trials and improvements in outcomes, a panel of experts reviewed the STEEP criteria to determine whether modifications are needed. METHODS We conducted systematic searches of ClinicalTrials.gov for adjuvant systemic and local-regional therapy trials for breast cancer to investigate if the primary end points reported met STEEP criteria. On the basis of common STEEP deviations, we performed a series of simulations to evaluate the effect of excluding non–breast cancer deaths and new nonbreast primary cancers from the invasive disease–free survival end point. RESULTS Among 11 phase III breast cancer trials with primary efficacy end points, three had primary end points that followed STEEP criteria, four used STEEP definitions but not the corresponding end point names, and four used end points that were not included in the original STEEP manuscript. Simulation modeling demonstrated that inclusion of second nonbreast primary cancer can increase the probability of incorrect inferences, can decrease power to detect clinically relevant efficacy effects, and may mask differences in recurrence rates, especially when recurrence rates are low. CONCLUSION We recommend an additional end point, invasive breast cancer–free survival, which includes all invasive disease–free survival events except second nonbreast primary cancers. This end point should be considered for trials in which the toxicities of agents are well-known and where the risk of second primary cancer is small. Additionally, we provide end point recommendations for local therapy trials, low-risk populations, noninferiority trials, and trials incorporating patient-reported outcomes.

Early prediction of neoadjuvant chemotherapy response by exploiting a transfer learning approach on breast DCE-MRIs

“…The main factors favouring the choice of NAC are a high ratio between the tumor volume and the breast volume, the presence of lymph node metastases, the young age of the patient and some histological parameters including the high tumor grading and the presence of specific molecular subtypes such as Triple Negative and HER2+ tumors 2 . Therefore, the proposed support tool could be helpful to drive any changes to the therapy in progress, i.e., dose-dense neoadjuvant chemotherapy 39 , introduction of new chemotherapy drugs or combination of chemotherapy and other drugs, such as trastuzumab 40 .…”

“…Alongside all these developments, the proposed tool can be extended to evaluate the efficacy of multiple neoadjuvant schemes early on. In this way, the probability of positively responding to therapy could be predicted and compared among the diverse NAC scenarios referred to the ASCO guidelines 40 . The medical experts could be able to prefer a tailored therapy pathway associated with the highest probability of positive response to therapy.…”

HER2 expression, copy number variation and survival outcomes in HER2-low non-metastatic breast cancer: an international multicentre cohort study and TCGA-METABRIC analysis

“…Clinical staging was used for patients that received neoadjuvant therapy. Outcome measures were RFS and OS, each defined according to STEEP version 2 [ 31 ].…”

FNTB Promoter Polymorphisms Are Independent Predictors of Survival in Patients with Triple Negative Breast Cancer

“…All statistical analyses were performed using GraphPad Prism 8.3 (GraphPad Software, La Jolla, CA, USA) and SPSS software version 25 (IBM, Armonk, NY, USA). The standardized definitions for efficacy end points (STEEP) criteria were used as endpoint definitions [26]. The primary endpoints of this study were recurrence-free interval (RFI), breast cancer-specific survival (BCSS) and overall survival (OS).…”