Multicenter phase 2 trial of neoadjuvant durvalumab plus chemotherapy for early triple-negative breast cancer: long-term analysis of GeparNuevo

The multicenter phase 2 GeparNuevo trial evaluated addition of durvalumab to neoadjuvant chemotherapy (NACT) in 174 patients with early triple-negative breast cancer (TNBC) cT1b-cT4a-d, and found that addition of durvalumab increased pathological complete response (pCR) rate versus placebo. Patients were randomized to receive durvalumab or placebo concurrently with nab-paclitaxel once per week and followed by dose-dense epirubicin and cyclophosphamide. Long-term analysis of the trial, with 86.4 months additional median follow-up compared to the previously reported 43.7 months, has now been published. Addition of durvalumab improved invasive disease-free survival (HR 0.56; p=0.0431), distant disease-free survival (HR 0.41; p=0.0069), and overall survival (HR 0.33; p=0.0085). All analyses were stratified by stromal tumor-infiltrating lymphocytes (sTILs) at baseline: low (≤10%), intermediate (11-59%), and high (≥60%). In exploratory subgroup analysis, patients with nodal involvement at baseline demonstrated a greater iDFS benefit. Post hoc analyses by sTILs high (>10%) versus low (≤10%) in residual disease showed 7-years iDFS rates 92.3% versus 51.4%. The authors conclude that addition of durvalumab to dose-dense NACT without adjuvant continuation of checkpoint inhibition improved long-term survival outcomes, irrespective of the extent of pathologic response. This underscores the necessity to re-evaluate the adjuvant continuation of checkpoint inhibition.