Abstract PO3-20-01: ASTEFANIA: a Phase III study of ado-trastuzumab emtansine plus atezolizumab or placebo as adjuvant therapy in patients with residual invasive breast cancer after neoadjuvant HER2-targeted therapy and chemotherapy
Authors: Schmid Peter , Bachelot Thomas , Bianchini Giampaolo , Harbeck Nadia , Loi Sherene , Park Yeon , Prat Aleix , Gilham Leslie , Boulet Thomas , Gochitashvili Nino , Monturus Estefania , Lambertini Chiara , Nyawira Beatrice , Knott Adam , Hurvitz Sara 
Published: May 2024

Abstract
BACKGROUND
Ado-trastuzumab emtansine (T-DM1) is the standard of care for adjuvant treatment of patients (pts) with HER2-positive early breast cancer (eBC) who have invasive residual disease after preoperative treatment with taxane and HER2-targeted therapy. However, a high unmet need remains in some higher risk subgroups (e.g., inoperable or lymph node-positive, hormone receptor-negative disease) who have 3-year invasive disease-free survival (IDFS) rates of 76%. Exploratory analyses suggest that addition of the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab to T-DM1 results in longer progression-free survival compared with T-DM1 alone in pts with previously treated PD-L1-positive metastatic BC. PD-L1/programmed death-1 inhibitors may have a different effect in eBC, as they result in improved pathologic complete response in early triple-negative BC regardless of PD-L1 status. ASTEFANIA evaluates atezolizumab plus T-DM1 in PD-L1-unselected pts with higher risk residual invasive breast cancer after neoadjuvant treatment.
TRIAL DESIGN
ASTEFANIA is a Phase III, randomized, double-blind, multicenter, study in pts with centrally confirmed HER2-positive eBC with residual invasive disease at surgery after neoadjuvant chemotherapy and HER2-directed treatment including ≥9 weeks of taxane and ≥9 weeks of trastuzumab. Within 12 weeks of primary surgery, pts are randomized 1:1 to intravenous (IV) T-DM1 3.6 mg/kg every 3 weeks (q3w) plus atezolizumab 1200 mg IV q3w or T-DM1 3.6 mg/kg IV q3w plus placebo IV q3w for 14 cycles. Radiotherapy and/or endocrine therapy is administered per local standards. Randomization is stratified by clinical stage at presentation, hormone receptor status, preoperative HER2-directed therapy, and PD-L1 status.
ELIGIBILITY CRITERIA
Eligible pts have clinical stage cT4/any N/M0, any cT/N2–3/M0, or cT1–3/N0–1/M0 at presentation. Those with cT1–3/N0–1 disease must have pathologic evidence of residual invasive carcinoma in axillary lymph node(s) at surgery. Pts with cT1mi/T1a/T1b/N0 disease are not eligible.
AIMS
The primary endpoint is IDFS. Secondary endpoints include overall survival, safety, and patient-reported outcomes.
STATISTICAL METHODS
The log-rank test will be used to compare IDFS between the treatment arms, according to the protocol-defined stratification factors. The Cox proportional hazards model, stratified by the protocol-defined stratification factors, will be used to estimate the hazard ratio between the two treatment arms and its 95% confidence intervals.
ACCRUAL
As of Jun 28, 2023, 789 pts of the target of 1,700 have been enrolled.
CONTACT INFORMATION
For more information or to refer a patient, email global.rochegenentechtrials@roche.com or call 1-888-662-6728 (USA only).
Clinicaltrials.gov number NCT04873362.
Originally presented at the ESMO Congress 2021, 202TiP, Peter Schmid et al. – Reused with permission.
Further information is available in Future Oncology 2022; 18:3563–3572. Submitted with permission from Future Medicine & Future Science, part of the Future Science Group.
Citation Format: Peter Schmid, Thomas Bachelot, Giampaolo Bianchini, Nadia Harbeck, Sherene Loi, Yeon Park, Aleix Prat, Leslie Gilham, Thomas Boulet, Nino Gochitashvili, Estefania Monturus, Chiara Lambertini, Beatrice Nyawira, Adam Knott, Sara Hurvitz. ASTEFANIA: a Phase III study of ado-trastuzumab emtansine plus atezolizumab or placebo as adjuvant therapy in patients with residual invasive breast cancer after neoadjuvant HER2-targeted therapy and chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-20-01.