Final analysis of WSG-ADAPT HER2+/HR- trial: Efficacy, safety, and predictive markers for 12-weeks of neoadjuvant dual blockade with trastuzumab + pertuzumab {+/-} weekly paclitaxel in HER2+/HR- early breast cancer (EBC).

518Background: In HER2+ EBC pCR rates after neoadjuvant chemo (CT)+/- anti-HER2 therapy differ according to hormone receptor (HR) status. The neoadjuvant ADAPT HER2+/HR- phase II trial aims to identify early responders (at 3 weeks) and evaluates the impact of additional paclitaxel (Pac) on pCR in patients receiving dual anti-HER2 blockade with trastuzumab + pertuzumab (T+P). Methods: 134 HER2+/HR-, cT1-4c, cN0/+ patients were randomized (2.5:1) to 12 weeks of neoadjuvant T+P ± weekly Pac (2/14-12/15). After surgery, standard therapy (CT+T) was recommended. Trial (planned n=220) tests non-inferiority of pCR (ypT0/is, ypN0) in T+P responders vs. T+P+Pac. Biomarkers are measured in baseline and 3-week biopsies. At the pre-planned interim analysis (IA), DSMB recommended 2ndIA (n=120) for validation of trial assumptions and re-evaluation of responder definition (Ki-67 drop u003e 30% or low cellularity). Results: Of the IA cohort 82 patients were evaluable for T+P and 38 for T+P+Pac. Baseline characteristics (T+P/T...