Abstract 248TiP
Background
TNBC is associated with higher percentages of pathological complete response (pCR) to NACT, and pts with a pCR have a favorable prognosis. However, pts with residual disease have a substantially higher risk of recurrence than pts with other subtypes of breast cancer (Liedke 2008, Hahnen 2017). Primary results have demonstrated clinically relevant efficacy and an acceptable safety profile of therapeutic blockade of PD-L1 binding by atezolizumab in pts with metastatic TNBC (Emens 2015, Schmidt 2015, Schmidt 2018). GeparDouze (NSABP B-59/GBG96) is an academic collaboration between NSABP and GBG. The aim is to determine whether the addition of atezolizumab to NACT and adjuvant therapy improves efficacy and to provide further data on safety of atezolizumab in pts with early TNBC.
Trial design
This is a phase III, double blind, placebo-controlled trial. 1520 pts are randomized 1:1 to receive atezolizumab/placebo 1200 mg IV q3wks concurrently with weekly paclitaxel 80 mg/m2 IV (12 doses) with carboplatin AUC 5 IV q3wks (4 doses) followed by epirubicin or doxorubicin/cyclophosphamide (EC/AC) every 2 or 3 wks (per investigators decision) for 4 doses. Following surgery, pts resume atezolizumab/placebo 1200 mg IV q3wks as adjuvant therapy for 6 months. Radiotherapy based on local standards is co-administered with atezolizumab/placebo. Stratification factors are Group (NSABP Foundation Inc.; GBG), tumor size (1.1-3.0cm; >3.0cm), EC/AC schedule (q2w; q3w), nodal status (positive; negative) and PD-L1 Status (positive; negative; indeterminate). Pts with centrally confirmed early TNBC and PD-L1-status can be enrolled. Primary tumor must be stage T2 or T3 or T1c and cN+. Co-primary endpoints are pCR (ypT0/Tis ypN0) and EFS. Main secondary endpoints are overall survival, recurrence-free interval, distant disease-free survival, and toxicity. Amendment #2 is currently under preparation to allow postneoadjuvant capecitabine for patients with non-pCR after NACT. As of 13-05-20, 679/1,520 pts have been randomized. The trial is financially supported by Genentech/Roche.
Clinical trial identification
NCT03281954.
Editorial acknowledgement
Legal entity responsible for the study
German Breast Group.
Funding
Genentech/Roche.
Disclosure
S. Loibl: Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards paid to institute: AbbVie ; Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards paid to institute: Amgen; Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards paid to institute: AstraZeneca; Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards paid to institute: Celgene; Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards paid to institute: Novartis; Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards paid to institute: Pfizer; Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards paid to institute: Roche; Honoraria (institution), honorario for lectures and ad boards paid to institute: Seattle Genetics; Honoraria (institution), honorarium for lectures paid to institute: PriME/ Medscape; Honoraria (self), lecture: Chugai; Research grant/Funding (institution): Teva; Research grant/Funding (institution): Vifor; Honoraria (institution), honorarioumpaid to institute: Daiichi Sankyo; Honoraria (institution), honorarium for ad boards paid to institute: Lilly; Honoraria (institution), honorarium for lectures and ad boards paid to institute: Samsung; Honoraria (institution), Advisor paid to institute: Eirgenix; Honoraria (institution), advisor honorarium paid to institute: BMS; Honoraria (institution), advisor honorarium paid to institute: Puma; Honoraria (institution), honorarium paid to insitute: MSD; Research grant/Funding (institution), paid to institue: Immunomedics; Licensing/Royalties, Immunsignature in TNBC: EP14153692.0 pending. P. Rastogi: Travel/Accommodation/Expenses, Travel and accommodations: AstraZeneca; Travel/Accommodation/Expenses, Travel and accommodations: Genentech/Roche; Travel/Accommodation/Expenses, Travel and accommodations: Lilly. S. Seiler: Research grant/Funding (institution), GeparOla study was supported by AstraZeneca: AstraZeneca; Advisory/Consultancy, Advisory Boards: Amgen; Advisory/Consultancy, Advisory Boards: Hexal; Honoraria (self), Presentations: Roche; Advisory/Consultancy, Advisory Boards: Mundipharma; Travel/Accommodation/Expenses, Travel costs: Novartis. C. Jackisch: Honoraria (self): AstraZeneca; Honoraria (self): Roche. P.C. Lucas: Shareholder/Stockholder/Stock options, Stock ownership: Amgen; Advisory/Consultancy, Spouse/Financial dependant, Consulting (spouse): Bayer/Loxo. C. Denkert: Honoraria (self): Novartis; Honoraria (self): Roche; Honoraria (self): MSD Oncology; Honoraria (self): Daiichi Sankyo; Research grant/Funding (institution): Myriad Genetics; Shareholder/Stockholder/Stock options, Cofounder and shareholder: Sividon Diagnostics / Myriad; Licensing/Royalties, cancer immunotherapy: EP18209672; Licensing/Royalties, therapy response: EP20150702464; Licensing/Royalties, Ki67 evaluator: Software (VMscope digital pathology). A. Poklepovic: Speaker Bureau/Expert testimony, Speakers Bureau: Bristol Myers Squibb; Advisory/Consultancy, Consulting: Novartis; Advisory/Consultancy, Consulting: Merck; Advisory/Consultancy, Consulting: Castle Biosciences. F. Moreno: Honoraria (self), Non-remunerated activity/ies: Pfizer; Honoraria (self), Non-remunerated activity/ies: Novartis; Honoraria (self), Non-remunerated activity/ies: Roche; Honoraria (self): MSD; Honoraria (self): AstraZeneca. E.P. Mamounas: Honoraria (self), Honoraria for Advisory Board and Speaker's Bureau: Genentech/Roche; Honoraria (self), Honoraria for Advisory Board and Speaker's Bureau: Exact Sciences; Honoraria (self), Honoraria for Advisory Board: Biotheranostics, Daiichi Sankyo; Honoraria (self), Consultant: Merck. Y. Lin: Honoraria (self): NSABP foundation. N. Wolmark: Honoraria (self), Service contract between NSABP Foundation, Inc. , Genentech/Roche: Genentech/Roche. C. Geyer: Honoraria (self), NSABP Foundation: Genentech/Roche; Honoraria (self), Non-financial support and Other, Travel/hotel expenses for Steering Committee activities: AstraZeneca; Honoraria (self), Non-financial support, medical writing support: AbbVie. All other authors have declared no conflicts of interest.