Abstract OT2-04-08: A randomized double-blind phase III clinical trial of neoadjuvant chemotherapy (NAC) with atezolizumab or placebo in patients (pts) with triple negative breast cancer (TNBC) followed by adjuvant atezolizumab or placebo: NSABP B-59/GBG 96-GeparDouze
Authors: Geyer Charles E , Loibl Sibylle , Rastogi Priya , Seiler Sabine , Costantino Joseph P , Nekljudova Valentina , Cortazar Patricia , Lucas Peter C , Denkert Carsten , Mamounas Eleftherios P , Jackish Christian , Wolmark Norman 
Published: March 2020

Background: TNBC is associated with higher percentages of pathological complete response (pCR) to neoadjuvant chemotherapy (NAC), and women with a pCR have a favorable prognosis. However, previous studies have found that women with residual disease have a substantially higher risk of recurrence than women with other subtypes of breast cancer. Additionally, other recent studies have found that therapeutic blockade of PD-L1 binding by atezolizumab has resulted in relevant anti-tumor efficacy. Design This is a phase III, double blind, placebo-control trial evaluating neoadjuvant atezolizumab with NAC followed by adjuvant atezolizumab in TNBC. Pts are stratified by region (North America; Europe), tumor size (1.1-3.0cm; &gt;3.0cm), AC/EC schedule (q2w; q3w), nodal status (positive; negative), and PD-L1 status (positive; negative or indeterminate) then randomized 1:1 to receive atezolizumab/placebo 1200 mg IV every 3 wks concurrently with both sequential regimens of weekly paclitaxel 80 mg/m2 IV for 12 doses with every 3-wk carboplatin AUC of 5 IV for 4 doses followed by AC/EC every 2-3 wks (per investigator discretion) for 4 cycles. Following surgery, pts resume atezolizumab/placebo 1200 mg IV every 3 wks as adjuvant therapy for 6 months. Radiotherapy based on local standards is co-administered with atezolizumab/placebo. Eligibility criteria Centrally-confirmed ER-neg, PR-neg, HER2-neg invasive breast cancer by ASCO/CAP guidelines. Primary tumor must be stage T2 or T3 if cN0 or cN1 with negative biopsy or T1c, T2, or T3 if cN1 with positive biopsy or cN2 or cN3. LVEF &gt;55% and no significant cardiac history. Statistical methods Co-primary endpoints are event-free survival (EFS) and pCR breast/nodes. Secondary endpoints include pCR breast, overall survival, distant disease-free survival, safety and toxicity. Trial is an academic collaboration between NSABP and GBG with support from Genentech/Roche. As of 7-8-19, 279/1,520 pts have been randomized. NCT03281954 Support: Genentech/Roche.

Citation Format: Charles E Geyer Jr., Sibylle Loibl, Priya Rastogi, Sabine Seiler, Joseph P Costantino, Valentina Nekljudova, Patricia Cortazar, Peter C Lucas, Carsten Denkert, Eleftherios P Mamounas, Christian Jackish, Norman Wolmark. A randomized double-blind phase III clinical trial of neoadjuvant chemotherapy (NAC) with atezolizumab or placebo in patients (pts) with triple negative breast cancer (TNBC) followed by adjuvant atezolizumab or placebo: NSABP B-59/GBG 96-GeparDouze [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT2-04-08.