Chemotherapy (CT) is the only treatment option in triple negative breast cancer (TNBC) since so far no targeted agents are available. High amounts of tumor infiltrating lymphocytes (TILs) in TNBC are associated with higher treatment response and better outcome. Immunotherapy alone or in combination might be used to increase pathological complete response (pCR, ypT0 ypN0). Adding an anti-PD-L1 checkpoint inhibitor (Durvalumab) to standard CT might be a valid option.
GeparNuevo will randomize patients to Durvalumab 1500 mg i.v. or placebo every 4 weeks. Monotherapy (750 mg i.v.) is given for the first 2 weeks (window phase), followed by a biopsy and Durvalumab/placebo plus nab-paclitaxel (nP) 125 mg/m2 weekly for 12 weeks followed by Durvalumab/placebo plus epirubicin/cyclophosphamide every 2 weeks for 4 cycles. Randomization will be stratified by TILs. Patients with primary cT1b-cT4a-d disease, centrally confirmed TNBC, and Ki-67 and TILs status on core biopsy can be included. Stromal TILs will be evaluated as no (≤10%) vs intermediate (11-59%) immune infiltrate vs lymphocyte predominant breast cancer (≥60%). PD-L1 status, immune markers and other predefined biomarkers will be prospectively assessed. Primary objective is to compare pCR rates. Secondary objectives are pCR rates in stratified subpopulations and according to other definitions; response rates; breast conservation rate; toxicity and compliance; quality of life; and survival. Change in TILs, Ki67 and other biomarkers before CT, after the window phase and after CT will be correlated with outcome. Six safety interim analyses focusing especially on immune-mediated adverse events are planned. It is planned to recruit 174 patients into this phase II trial. Recruitment has started in QII/2016 and is planned for 18 months in 30 sites in Germany.
Legal entity responsible for the study
German Breast Group
All authors have declared no conflicts of interest.