Abstract 202TiP
Background
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 pre-operative treatment with taxane and HER2-targeted therapy. However a high unmet need remains in some higher risk subgroups (eg, 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 PD-L1 inhibitor atezolizumab to T-DM1 results in longer progression-free survival compared to T-DM1 alone in pts with previously treated PD-L1-positive metastatic BC. PD-L1/PD-1 inhibitors may have a different effect in eBC as they result in improved pCR 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 (EudraCT#2020-003681-40) is a phase 3, 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. Eligible pts have clinical stage cT4/anyN/M0, any cT/N2–3/M0, or cT1-3/N0-1/M0 at presentation. Pts with cT1mi/T1a/T1b/N0 disease are not eligible. Those with cT1-3/N0-1 disease must have pathologic evidence of residual invasive carcinoma in axillary lymph node(s) at surgery. Within 12 weeks of primary surgery, pts are randomized 1:1 to T-DM1 3.6 mg/kg IV q3w plus atezolizumab 1200 mg IV q3w or T-DM1 3.6 mg/kg IV q3w plus atezolizumab-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. The primary endpoint is IDFS. Secondary endpoints include overall survival, safety, and patient-reported outcomes. Approximately 1590 pts will be enrolled.
Clinical trial identification
EudraCT 2020-003681-40.
Editorial acknowledgement
Medical writing support was provided by Holly Strausbaugh, PhD of Twist Medical, LLC, and funded by F. Hoffmann-La Roche, Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
P. Schmid: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Puma; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Oncogenex; Financial Interests, Institutional, Research Grant: Roche; Other, Spouse - Employee: Roche. T. Bachelot: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other, Steering Committee Member: Roche; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: SeaGen. G. Bianchini: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Neopharm Israel; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Genomic Health; Financial Interests, Personal, Advisory Board: EISAI; Financial Interests, Personal, Other, travel grants: Roche; Financial Interests, Personal, Other, travel grants: Pfizer; Financial Interests, Personal, Other, travel grants: AstraZeneca; Financial Interests, Personal, Other, travel grants: EISAI; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Training: MSD; Financial Interests, Personal, Training: Pfizer. N. Harbeck: Financial Interests, Personal, Advisory Role, honoraria: AstraZeneca; Financial Interests, Personal, Advisory Role, honoraria: Daiichi Sankyo; Financial Interests, Personal, Advisory Role, honoraria: Lilly; Financial Interests, Personal, Advisory Role, honoraria: MSD; Financial Interests, Personal, Advisory Role, honoraria: Novartis; Financial Interests, Personal, Advisory Role, honoraria: Pierre Fabre; Financial Interests, Personal, Advisory Role, honoraria: Pfizer; Financial Interests, Personal, Advisory Role, honoraria: Roche; Financial Interests, Personal, Advisory Role, honoraria: Sandoz/Hexal; Financial Interests, Personal, Advisory Role, honoraria: Seattle Genetics; Non-Financial Interests, Personal, Ownership Interest: West German Study Group (WSG). S. Loi: Financial Interests, Institutional, Expert Testimony, Consultant: Aduro Biotech; Financial Interests, Institutional, Advisory Board, Consultant: Novartis; Financial Interests, Institutional, Advisory Board, Consultant: GlaxoSmithKline; Financial Interests, Institutional, Advisory Board, Consultant: Roche Genentech; Financial Interests, Institutional, Advisory Board, Consultant: AstraZeneca; Financial Interests, Institutional, Advisory Board, Consultant: Silverback Therapeutics; Financial Interests, Institutional, Advisory Board, Consultant: G1 Therapeutics; Financial Interests, Institutional, Funding, Research: Novartis; Financial Interests, Institutional, Funding, Research: BMS; Financial Interests, Institutional, Funding, Research: Merck; Financial Interests, Institutional, Funding, Research: PUMA Biotechnology; Financial Interests, Institutional, Funding, Research: Eli Lilly; Financial Interests, Institutional, Funding, Research: Nektar Therapeutics; Financial Interests, Institutional, Funding, Research: AstraZeneca; Financial Interests, Institutional, Funding, Research: Seattle Genetics; Non-Financial Interests, Personal, Advisory Role, Consultant (non-renumerated): Novartis; Non-Financial Interests, Personal, Advisory Role, Consultant (non-renumerated): Bristol Myers Squibb; Non-Financial Interests, Personal, Advisory Role, Consultant (non-renumerated): Seattle Genetics; Non-Financial Interests, Personal, Advisory Role, Consultant (non-renumerated): Merck; Non-Financial Interests, Personal, Advisory Role, Consultant (non-renumerated): AstraZeneca; Non-Financial Interests, Personal, Advisory Role, Consultant (non-renumerated): Roche Genentech; Financial Interests, Institutional, Funding, Research: Roche Genentech; Financial Interests, Institutional, Advisory Board, Consultant: PUMA Biotechnologies; Financial Interests, Institutional, Advisory Board, Consultant: Pfizer; Financial Interests, Institutional, Advisory Board, Consultant: Seattle Genetics; Financial Interests, Institutional, Advisory Board, Consultant: Bristol Meyers Squibb; Financial Interests, Personal, Advisory Role, Scientific Advisory Board Member: Akamara Therapeutics; Financial Interests, Personal, Other: National Breast Cancer Foundation of Australia Endowed Chair; Financial Interests, Personal, Other: Breast Cancer Research Foundation, New York. Y.H. Park: Non-Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant, Contracted research: AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: AstraZeneca; Non-Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Institutional, Funding, Contracted research: Pfizer; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Pfizer; Non-Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Funding, Contracted research: Roche; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Roche; Financial Interests, Personal, Other, Speaker fee: Roche; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Daiichi Sankyo; Non-Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Other, Speaker fee: Novartis; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Novartis; Non-Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Institutional, Funding, Contracted research: Merck; Non-Financial Interests, Institutional, Principal Investigator, Contracted research: Merck; Non-Financial Interests, Personal, Other, Medical writing support for this abstract: Roche. A. Prat: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Role, Consultancy: Roche; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Role, Consultancy: Pfizer; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Role, Consultancy: Novartis; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Role, Consultancy: Amgen; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Role, Consultancy: BMS; Financial Interests, Personal, Invited Speaker: Nanostring Technologies; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Advisory Role, Consultancy: Puma; Financial Interests, Personal, Advisory Role, Consultancy: Oncolytics Biotech; Financial Interests, Personal, Advisory Role, Consultancy: MSD; Financial Interests, Personal, Advisory Role, Consultancy: Guardan Health; Financial Interests, Personal, Advisory Role, Consultancy: Peptomyc; Financial Interests, Personal, Advisory Role, Consultancy: Lilly; Financial Interests, Personal, Leadership Role: Reveal Genomics, SL; Financial Interests, Institutional, Funding, Contracted research, Clinical trials: Boehringer Ingelheim; Financial Interests, Institutional, Funding, Contracted research, Clinical trials: Novartis; Financial Interests, Institutional, Funding, Contracted research, Clinical trials: Roche; Financial Interests, Institutional, Funding, Contracted research: Nanostring Tecnologies; Financial Interests, Institutional, Invited Speaker: Nanostring Tecnologies; Financial Interests, Institutional, Funding, Contracted research: Sysmex Europa GmbH; Financial Interests, Institutional, Funding, Contracted research: Medica Scientia inno. Research, SL; Financial Interests, Institutional, Funding, Contracted research: Celgene; Financial Interests, Institutional, Funding, Contracted research: Astellas; Financial Interests, Institutional, Funding, Contracted research: Pfizer; Financial Interests, Institutional, Funding, Clinical trials: Roche; Financial Interests, Institutional, Funding, Clinical trials: Amgen; Financial Interests, Institutional, Funding, Clinical trials: Daiichi Sankyo; Other, Personal, Leadership Role, Executive board: Reveal Genomics, SL; Other, Personal, Leadership Role, Executive board: Beast International Group (BIG); Other, Personal, Leadership Role, Executive board: SOLTI cooperative group; Other, Personal, Leadership Role, Patronage committee: Actitud Frente al Cáncer Foundation. L. Gilham: Financial Interests, Personal, Advisory Role: Roche; Non-Financial Interests, Personal, Advisory Role: Breast Cancer Trials (Australia & New Zealand). T. Boulet: Financial Interests, Institutional, Full or part-time Employment, Employee of PAREXEL International GmbH contracted by F. Hoffmann-La Roche Ltd.: N. Gochitashvili: Financial Interests, Personal, Full or part-time Employment: Roche. E. Monturus: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche; Financial Interests, Institutional, Sponsor/Funding: F. Hoffmann-La Roche. C. Lambertini: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Stocks/Shares: F. Hoffmann-La Roche Ltd. B. Nyawira: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche. A. Knott: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. S.A. Hurvitz: Financial Interests, Personal, Ownership Interest, spouse: Ideal Implant; Financial Interests, Personal, Stocks/Shares, stock options: NK Max; Financial Interests, Personal, Stocks/Shares, spouse owns: ROM Tech; Financial Interests, Institutional, Research Grant: Ambrx; Financial Interests, Institutional, Principal Investigator, local PI: Ambrx; Financial Interests, Institutional, Principal Investigator, local PI: Arvinas; Financial Interests, Institutional, Principal Investigator, local PI: AstraZeneca; Financial Interests, Institutional, Principal Investigator, coordinating PI: Bayer; Financial Interests, Institutional, Principal Investigator, coordinating PI: Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator, local PI: Dignitana; Financial Interests, Institutional, Principal Investigator, local PI: Genentech/Roche; Financial Interests, Institutional, Principal Investigator, local PI: Gilead; Financial Interests, Institutional, Principal Investigator, local PI: GSK; Financial Interests, Institutional, Principal Investigator, local PI: Immunomedics; Financial Interests, Institutional, Principal Investigator, local PI: Lilly; Financial Interests, Institutional, Principal Investigator, local PI: Macrogenics; Financial Interests, Institutional, Principal Investigator, local PI: Novartis; Financial Interests, Institutional, Principal Investigator, local PI: OBI Pharma; Financial Interests, Institutional, Principal Investigator, local PI: Pfizer; Financial Interests, Institutional, Principal Investigator, local PI: Phoenix Molecular Designs, Ltd; Financial Interests, Institutional, Principal Investigator, local PI: Pieris; Financial Interests, Institutional, Principal Investigator, local PI: PUMA; Financial Interests, Institutional, Principal Investigator, local PI: Radius; Financial Interests, Institutional, Research Grant: Samumed; Financial Interests, Institutional, Principal Investigator, local PI: Sanofi; Financial Interests, Institutional, Principal Investigator, local PI: Seattle Genetics; Financial Interests, Institutional, Principal Investigator, local PI: Zymeworks.