A new predictive biomarker of immunotherapy benefit in triple-negative breast cancer was validated in the NeoTRIP trial

The new DetermaIO assay, a 27-gene immune-related signature, has been demonstrated as a predictive biomarker of immunotherapy benefit over chemotherapy alone in triple-negative breast cancer, as shown recently on Clinical Cancer Research.

The DetermaIO assay is a 27-gene signature that captures the phenotype of the tumor immune microenvironment and is predictive of benefit form immune checkpoint inhibitors in different tumor types.

Authors evaluated the 27-gene RT-qPCR based DetermaIO assay in pre-treatment core biopsies from patients with stage II/III triple negative breast cancer enrolled in the NeoTRIPaPDL1 phase III randomized trial comparing neoadjuvant carboplatin/nab-paclitaxel chemotherapy (CT) plus atezolizumab (n=242) with CT alone (n=220). The DetermaIO assay was further evaluated in expression data from patients treated with paclitaxel plus pembrolizumab or paclitaxel alone in the I-SPY2 trial. Results showed the predictive value of response to immunotherapy of DetermaIO assay: in NeoTRIPaPDL1, DetermaIO positive cancers (41.8%) had pathologic complete response rates of 69.8% and 46.9% in the CT+atezolizumab and CT arms, respectively. In I-SPY2, DetermaIO positive cancers (45.9%) had pathologic complete response rates of 85.7% and 16%, with and without immunotherapy, respectively. These results show that «the 27-gene DetermaIO assay can identify the subset of patients with triple negative breast cancer that experienced improvement in pathologic complete response rate when atezolizumab was added to neoadjuvant chemotherapy», as authors say. «Based on these results, a prospective study or registry could be designed to directly test the clinical utility of the assay. Also considering the results available in other malignancies, the DetermaIO assay is emerging as a clinically available predicitve tool that may identify patients who may benefit from the addition of immunotherapy to standard neoadjuvant chemotherapy: only patients with DetermaIO-positive tumors have significantly higher likelihood of achieving pathologic complete response when treated with chemotherapy in combination with immunotherapy. Our results confirm DetermaIO as a predictive biomarker of immunotherapy benefit», authors conclude.