A randomized, double-blind, phase III trial of neoadjuvant chemotherapy with Atezolizumab/Placebo in patients with triple-negative breast cancer followed by adjuvant continuation of Atezolizumab/Placebo (GeparDouze)

Background:

TNBC is associated with higher percentages of pathological complete response (pCR) to neoadjuvant chemotherapy (NACT), and women with a pCR have a favorable prognosis. However, women with residual disease have a substantially higher risk of recurrence than women with other subtypes of breast cancer (Liedtke 2008, Loibl 2017). Therapeutic blockade of PD-L1 binding by atezolizumab has resulted in relevant anti-tumor efficacy (Adams 2017, Schmid 2017).

Methods:

GeparDouze (NSABP B-59/GBG96) will randomize (1:1) 1520 patients to NACT + atezolizumab 1200 mg or placebo IV every 3 wks followed by continuation of atezolizumab 1200 mg or placebo IV as adjuvant therapy for 6 months, stratified by region (North America; Europe), tumor size (1.1 – 3.0 cm; > 3.0 cm), epirubicin or doxorubicin/cyclophosphamide (EC/AC, q2w; q3w), and nodal status (positive; negative). Patients with primary cT1c-cT3 TNBC and centrally assessed hormone receptor-status, HER2-status, Ki-67, and sTILs on core biopsy can be enrolled. Co-primary endpoints are pCR (ypT0/Tis ypN0) and event free survival (EFS). Main secondary endpoints are overall survival, recurrence-free interval, distant disease-free survival, and toxicity.

Results:

GeparDouze is being conducted as an academic collaboration between GBG and NSABP. So far, 2 patients are enrolled. Accrual for this study will be 1,520 randomized patients. It is expected that approximately 760 patients will be randomized within 33 months by North American sites and approximately 760 patients by European sites.

Conclusions:

The aim of GeparDouze is to determine whether the addition of atezolizumab to NACT and adjuvant therapy improves pCR and EFS in patients with TNBC.