Investigating Denosumab as an add-on neoadjuvant treatment for RANK/L-positive or RANK/L-negative primary breast cancer and two different nab-Paclitaxel schedules – 2 × 2 factorial design (GeparX)

Background:

The GeparX study aims to investigate denosumab in patients with primary BC as an adjunct to neoadjuvant chemotherapy (NACT) for its ability to increase pCR rates and improve outcome overall and in relation to RANK/L expression.

Methods:

GeparX will randomize 778 patients to NACT+/-denosumab (120 mg s.c. q4w for 6 cycles), stratified by lymphocyte predominant BC (≤50% vs. > 50% stromal tumor infiltrating lymphocytes [sTILs]), subtype (HER2-/HR+ vs. triple negative (TNBC) vs. HER2+), and epirubicin/cyclophosphamide (EC, q2w vs. q3w). In addition, patients are randomized to different taxane backbones: nab-paclitaxel (nP) 125 mg/m² weekly+EC or nP 125 mg/m² day 1,8 q22+EC. TNBC receive carboplatin and HER2+ BC ABP 980, a trastuzumab biosimilar+pertuzumab. Patients with primary cT1c-cT4a-d BC and centrally assessed HR, HER2, Ki-67, sTILs and RANK status on core biopsy can be enrolled.

Co-primary objectives compare the pCR (ypT0 ypN0) rates of NACT+/-denosumab and the pCR rates between the two backbone treatments. Secondary objectives are interaction of denosumab treatment with RANK expression; pCR per arm for both randomizations in TNBC and HER2+ BC; pCR in RANK high vs. low; other pCR definitions for both randomizations; response rates; breast conservation rates; toxicity and compliance; survival.

Results:

So far, 258 patients (25 patients with HER2+ BC) are enrolled.

Conclusions:

GeparX investigates if the addition of denosumab to anthracycline/taxane-containing NACT will increase the pCR rate and which nP schedule to prefer in primary BC. In addition, safety and efficacy of ABP 980+pertuzumab as part of NACT for the treatment of HER2+ BC will be evaluated.