Diversity, inclusion, and patient (pt)-centricity in the randomized, double-blind, phase III ASTEFANIA study of ado-trastuzumab emtansine (T-DM1) ± atezolizumab in pts with HER2-positive early breast cancer (EBC) with residual invasive disease after preoperative chemotherapy and anti-HER2 therapy.
Authors: Rogerson Sarah , Turner Howard , Bilkhu Angela , Monturus Estefania , Knott Adam , Restuccia Eleonora , Quashie Nigel , Wheatley Duncan , Gilham Leslie , Hurvitz Sara A. , Schmid Peter , Bachelot Thomas , Bianchini Giampaolo , Harbeck Nadia , Loi Sherene , Park Yeon Hee , Prat Aleix , Simkins Tracy 
Published: June 2022

e12504

Background: Representative pt populations in clinical trials are essential to address healthcare disparities between different racial/ethnic groups, including treatment access and pt outcomes. Many clinical trials mainly include White pts, which may limit the generalizability of the results to the global population. A framework that was recently developed by Genentech for improving inclusion of underrepresented pt groups, as well as the CHIMES (NCT04377555) and EMPACTA (NCT04372186) studies, have all shown the feasibility of inclusive studies. ASTEFANIA (NCT04873362) is a pt-centric study, which includes pt/investigator collaboration to keep a pt focus and tactics to recruit a diverse population and enable participation of underserved communities. We report early recruitment data. Methods: Global/local initiatives and inclusive eligibility criteria remove barriers to enrollment of underserved pts and support treatment journeys. Eligible pts (Eastern Cooperative Oncology Group performance status of 0/1; no prior immune checkpoint inhibitor treatment) are randomized 1:1 to T-DM1 (3.6 mg/kg) + atezolizumab (1200 mg)/placebo every 3 weeks for 14 cycles (stratification factors: clinical stage, hormone receptor status, preoperative anti-HER2 therapy, PD-L1 status). Primary endpoints: IDFS in intention-to-treat and PD-L1-positive populations. Secondary endpoints include overall survival, patient-reported outcomes (PROs), and safety. To remove pt access barriers and ease pt burden, consent and PRO forms are available in multiple languages, mobile nursing/telemedicine is planned for pts in rural areas, a wellness app and culturally sensitive support videos are being created, and financial support is provided for study-related expenses and loss of earnings. Results: Recruitment began in May 2021. By Feb 9, 2022, 236 pts were randomized: 147 White (62%), 72 Asian (31%; Indian [n = 4], Korean [46], Chinese [16], other [6]), 10 Hispanic (4%; 5 of whom also identify as American Indian), 2 Black (1%), and 5 pts (2%) whose race/ethnicity was unreported/unknown. Of these, 27 (11%) have received financial support. Enrollment in Africa begins later this year. Mobile nursing/telemedicine is planned for 14 countries. Conclusions: As the first study of its kind in HER2-positive EBC, ASTEFANIA actively aims to be accessible and include pts from a range of races/ethnicities and socially underserved backgrounds. There is a growing need for more compassionate and inclusive research. To do this, forward planning of pt-centric studies is essential to reduce the burden on study resources. We hope that the tactics outlined here will allow us to achieve our goals of inclusive research. Clinical trial information: NCT04873362.