Investigating denosumab as add-on neoadjuvant treatment for hormone receptor-negative, RANK-positive or RANK-negative primary breast cancer and two different nab-Paclitaxel schedules - 2x2 factorial design (GeparX).

Abstract

TPS635Background: RANK ligand (RANKL) functions via its receptor RANK and pharmacologic inhibition attenuates breast cancer (BC) development and metastatic progression. High RANK expression is associated in hormone receptor negative (HR-) BC with higher pathological complete response (pCR) rates. Denosumab, an antibody against RANKL, will be tested in patients with HR- primary BC in addition to neoadjuvant chemotherapy (NACT). Methods: GeparX will randomize 778 patients to NACT +/- denosumab (120mg sc every 4 weeks for 6 cycles), stratified by lymphocyte predominant BC ( ≤ 50% vs > 50% stromal tumor infiltrating lymphocytes [TILs]), HER2 status, and epirubicin/cyclophosphamide (EC, q2w vs q3w). Secondarily patients will be randomized to the backbone treatment of nab-paclitaxel (nP) 125mg/m² weekly + EC or nP 125mg/m² day 1,8 q22 + EC, stratified by the first randomization. Carboplatin will be given in triple negative (TNBC) and trastuzumab + pertuzumab in HER2+ BC. Patients with primary cT1c-cT4a-d BC, ce...