Gene Expression Test May Predict Added Atezolizumab Benefit in TNBC

“We demonstrated that the 27-gene DetermaIO assay can identify the subset of [patients with] TNBC [who] experienced an improvement in pCR rate when atezolizumab was added to neoadjuvant [chemotherapy],” according to the authors of the phase 2 neoTRIPaPDL1 trial (NCT002620280).

Use of the gene expression test DetermaIO™ identified patients with triple-negative breast cancer (TNBC) who were most likely to benefit from the addition of immunotherapy with atezolizumab (Tecentriq) to neoadjuvant chemotherapy, according to findings from the phase 2 neoTRIPaPDL1 trial (NCT002620280) published in Clinical Cancer Research.¹

Data showed that 69.8% (n = 30/43) of patients in the atezolizumab/chemotherapy arm who had a positive test result with DetermaIO experienced a pathologic complete response (pCR) compared with 46.9% of those with a positive outcome in the chemotherapy arm (P = .043). Among patients with a negative DetermaIO test result, the pCR rate was 44.6% (n = 29/65) with atezolizumab plus chemotherapy vs 49.2% in the chemotherapy alone arm.

When analyzing PD-L1 immunohistochemistry, stromal tumor-infiltrating lymphocytes, and 11 immune signatures, only DetermaIO showed significance for interaction, suggesting it may predict patients who are most likely to experience a pCR with the addition of atezolizumab to chemotherapy.² Across an unselected patient population, atezolizumab plus chemotherapy produced a pCR rate of 48.6% compared with 44.4% in the chemotherapy alone arm; this numerical improvement did not reach statistical significance (P = .48).

Investigators further assessed the validity of DetermaIO by using gene expression data from the phase 2 I-SPY2 trial (NCT01042379) associated with patients with TNBC who received pembrolizumab (Keytruda) plus chemotherapy or chemotherapy alone. In the pembrolizumab/chemotherapy arm, the pCR rate was 85.7% among those with a positive DetermaIO result and 46.7% among those with a negative result (odds ratio [OR], 6.86; 95% CI, 1.12-41.83; P = .037). In the chemotherapy alone arm, the pCR rates were 16% for patients with a positive result and 16% for those with a negative result (OR, 0.99; 95% CI, 0.24-4.16; P = .990).

“We demonstrated that the 27-gene DetermaIO assay can identify the subset of [patients with] TNBC [who] experienced an improvement in pCR rate when atezolizumab was added to neoadjuvant [chemotherapy],” Matteo Dugo, from the Department of Medical Oncology at IRCCS Ospedale San Raffaele, Milan, Italy, and coauthors wrote.¹ “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 diagnostic tool that may identify patients who do not experience improved pCR rate with neoadjuvant immune checkpoint therapy.”

In the multi-center, open-label NeoTRIP trial, 280 patients with stage II/III TNBC were assigned to receive neoadjuvant carboplatin at area under the curve 2 plus nab-paclitaxel at 125 mg/m² intravenously on days 1 and 8 alone (n = 142) or in combination with atezolizumab at 1200 mg intravenously on day 1 (n = 138). Treatment in both arms continued every 3 weeks for 8 cycles before patients underwent surgery.

The trial’s primary end point was event-free survival (EFS).3 Secondary end points included pCR, clinical objective response, distant EFS, and safety and tolerability.

Patients 18 years and older with early high-risk and locally advanced or inflammatory breast cancers, histologically confirmed unilateral breast cancer with invasive ductal histology not otherwise specified of high proliferation or grade, and HER2-negative disease were eligible for enrollment on the trial.

“We are thankful for the support from Matteo Dugo and his team and are thrilled that the data in this clinical trial and this publication clearly demonstrate that DetermaIO can identify patients who are more likely to benefit from immunotherapy,” Josh Riggs, chief executive officer at Oncocyte, the developers of DetermaIO, stated in a press release on these findings.²

References

1. Dugo M, Huang C-S, Egle D, et al. The immune-related 27-gene signature DetermaIO predicts response to neoadjuvant atezolizumab plus chemotherapy in triple-negative breast cancer. Clinical Cancer Research. 2024. doi:10.1158/1078-0432.CCR-24-0149
2. Oncocyte’s DetermaIO immuno-oncology assay predicts response to atezolizumab in phase 2 clinical trial. News release. Oncocyte Corp. October 8, 2024. Accessed October 9, 2024. https://tinyurl.com/3b3vv2u2
3. Neoadjuvant therapy in TRIPle Negative Breast Cancer With antiPDL1 (NeoTRIPaPDL1). ClinicalTrials.gov. Updated June 3, 2024. Accessed October 9, 2024. https://tinyurl.com/3s56x5du