Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 platform trial

Durvalumab with olaparib was one of the experimental regimens evaluated in I-SPY 2, a neoadjuvant platform trial for high risk, early stage breast cancer, and graduated in the HER2- and HR+HER2- signatures. We hypothesized that (pre-treatment) expression-based immune signatures may predict response to the immune checkpoint inhibitor durvalumab and signatures related to DNA repair deficiency (DRD) may associate with response to olaparib. In this analysis, we assessed 13 expression based signatures related to immune, DRD, proliferation and estrogen signaling as specific predictor of pathologic complete response (pCR) to durvalumab/olaparib. RNA extracted from pretreatment biopsies were profiled using Agilent 44 K expression arrays (GPL20078). I-SPY2 changed biopsy requirements from fresh frozen (FF) tissue to formalin fixed paraffin embedded (FFPE) tissues in May 2018; therefore, patients on the durvalumab/olaparib arm had RNA extracted from FFPE biopsies (N=71). As microarray-based gene expression levels may differ between FF and FFPE tissues, we restricted the control set in the biomarker analysis to patients who received treatment in the control arm and had FFPE-derived gene expression data (N=34). The sample characteristics and their values represent: HER2: the status of the HER2 gene. 1 = positive; 0 = negative. HR: the status of hormone (estrogen and progesterone) receptors 1 = positive; 0 = negative. pCR: the status of a pathological complete response (pCR) 1 = complete response; 0 = failed complete response MP: MP status MammaPrint High 1: 0 ; MammaPrint (ultra)-High2: 1 . Arm: arm of the trial per patient ‘durvalumab/olaparib’; control