A gene expression test, DetermaIO, shows promise in predicting which patients with triple-negative breast cancer (TNBC) are most likely to benefit from the addition of atezolizumab (Tecentriq) to neoadjuvant chemotherapy. Findings from the phase 2 neoTRIPaPDL1 trial, published in Clinical Cancer Research, indicate that DetermaIO can identify a subset of TNBC patients who experience a significant improvement in pathologic complete response (pCR) rates when treated with atezolizumab in combination with chemotherapy.
The multi-center, open-label NeoTRIP trial involved 280 patients with stage II/III TNBC. Patients were randomized to receive either neoadjuvant carboplatin plus nab-paclitaxel, or the same chemotherapy regimen in combination with atezolizumab. The primary endpoint was event-free survival (EFS), with pCR as a secondary endpoint.
DetermaIO Predicts pCR Improvement
The study revealed that among patients in the atezolizumab/chemotherapy arm, 69.8% (n = 30/43) who tested positive with DetermaIO achieved a pCR, compared to 46.9% in the chemotherapy-only arm (P = .043). Conversely, in patients with a negative DetermaIO result, the pCR rate was 44.6% (n = 29/65) with atezolizumab plus chemotherapy versus 49.2% in the chemotherapy-alone arm. This suggests that atezolizumab provides a significant benefit only to patients identified as DetermaIO-positive.
Validation with Pembrolizumab Data
To further validate these findings, investigators analyzed gene expression data from the phase 2 I-SPY2 trial, focusing on TNBC patients treated with pembrolizumab (Keytruda) plus chemotherapy or chemotherapy alone. The results mirrored those of the neoTRIPaPDL1 trial. In the pembrolizumab/chemotherapy arm, the pCR rate was 85.7% among DetermaIO-positive patients and 46.7% among DetermaIO-negative patients (odds ratio [OR], 6.86; 95% CI, 1.12-41.83; P = .037). In the chemotherapy-alone arm, pCR rates were 16% for both DetermaIO-positive and -negative patients (OR, 0.99; 95% CI, 0.24-4.16; P = .990).
Clinical Implications and Future Directions
According to Matteo Dugo, from the Department of Medical Oncology at IRCCS Ospedale San Raffaele, Milan, Italy, the 27-gene DetermaIO assay can effectively identify the subset of TNBC patients who experience an improved pCR rate when atezolizumab is added to neoadjuvant chemotherapy. He suggests that a prospective study or registry could be designed to directly test the clinical utility of the assay.
Josh Riggs, chief executive officer at Oncocyte, the developers of DetermaIO, expressed enthusiasm for the data, stating that it clearly demonstrates DetermaIO's ability to identify patients more likely to benefit from immunotherapy. Oncocyte is now seeking reimbursement coverage from the Centers for Medicare and Medicaid Services (CMS) to broaden access to this test.
The study highlights the potential of DetermaIO as a clinically valuable diagnostic tool for identifying patients who will benefit from immune checkpoint therapy in the neoadjuvant setting for TNBC.
