The Immune-Related 27-Gene Signature DetermaIO Predicts Response to Neoadjuvant Atezolizumab plus Chemotherapy in Triple-Negative Breast Cancer
Matteo Dugo, Chiun‐Sheng Huang, Daniel Egle, Begoña Bermejo, C. Zamagni, Robert S. Seitz, Tyler J. Nielsen, Marc Thill, Antonio Antón, Stefania Russo, Eva Ciruelos, Brock L. Schweitzer, Douglas Teller Ross, Barbara Galbardi, Richard Greil, Semiglazov Vf, Balázs Győrffy, Marco Colleoni, Catherine M. Kelly, Gabriella Mariani, Lucia Del Mastro, Olivia Blasi, Maurizio Callari, Lajos Pusztai, Pinuccia Valagussa, Giuseppe Viale, Luca Gianni, Giampaolo Bianchini
Abstract
PURPOSE: We assessed the 27-gene RT-qPCR-based DetermaIO assay and the same score calculated from RNA sequencing (RNA-seq) data as predictors of sensitivity to immune checkpoint therapy in the neoTRIPaPDL1 randomized trial that compared neoadjuvant carboplatin/nab-paclitaxel chemotherapy (CT) plus atezolizumab with CT alone in stage II/III triple-negative breast cancer. We also assessed the predictive function of the immuno-oncology (IO) score in expression data of patients treated with pembrolizumab plus paclitaxel (N = 29) or CT alone (N = 56) in the I-SPY2 trial. EXPERIMENTAL DESIGN: RNA-seq data were obtained from pretreatment core biopsies from 242 (93.8%) of the 258 patients in the per-protocol-population. The DetermaIO RT-qPCR test, performed in the CAP/CLIA-accredited laboratory of Oncocyte Corp., was available for 220 patients (85.3%). A previously established threshold was used to assign DetermaIO-positive versus DetermaIO-negative status. Publicly available microarray data were used from I-SPY2. RESULTS: IO scores calculated from RNA-seq and RT-qPCR data were highly concordant. In neoTRIPaPDL1, DetermaIO-positive cancers (N = 92, 41.8%) had pathologic complete response (pCR) rates of 69.8% and 46.9% in the CT + atezolizumab and CT arms, respectively. In DetermaIO-negative cases, pCR rates were similar in both arms (44.6% vs. 49.2%; interaction test P = 0.04). PDL1 protein expression and stromal tumor-infiltrating lymphocyte count were not predictive of differential benefit from atezolizumab. In I-SPY2, IO-positive cancers (45.9%) had pCR rates of 85.7% and 16%, with and without immunotherapy, respectively. In IO-negative cancers, pCR rates were 46.7% versus 16.1%. CONCLUSIONS: DetermaIO identified patients who benefited from neoadjuvant immunotherapy resulting in improved pCR rate, independently of PDL1.