Chemo-Free Durvalumab + Trastuzumab + Pertuzumab Yields 49% pCR (68% RCB0/1) in HER2-Enriched Early Breast Cancer

The single-arm Phase II DTP trial (NCT03820141) treated 39 stage I–III, ER/PR-negative, (by a BluePrint [BP] 80-gene molecular subtyping test that classifies early-stage breast cancer (EBC) into Basal, Luminal, and HER2 subtypes) tumors with six 3-weekly cycles of the PD-L1 antibody durvalumab plus dual HER2 blockade (trastuzumab 6 mg/kg Q3W, pertuzumab 420 mg Q3W) without chemotherapy; 37 were evaluable. Pathologic complete response reached 18/37 (48.6%) and overall RCB0/1 25/37 (67.6%). pCR correlated positively with stromal TILs (p = 0.02) and PD-L1 CPS (p = 0.038) and inversely with tumor size and node positivity. Only five grade 3 AEs occurred, versus the ≥40% grade 3–4 toxicity typical of taxane-based regimens. Notably, this chemo-free pCR rivals the 49% achieved by docetaxel + trastuzumab + pertuzumab in the NeoSphere trial and far surpasses the 17% pCR seen with trastuzumab + pertuzumab alone.