59 DetermaIO (IO score) is associated with efficacy of ICI monotherapy in advanced NSCLC patients: a retrospective BC Cancer study
Bibliographic record
Abstract
<h3>Background</h3> Immune checkpoint inhibitors (ICI), either as monotherapy or in combination with platinum-based chemotherapy, is standard of care in aNSCLC. However, most patients do not respond to ICI therapy, even when PD-L1≥50% (PD-L1 high). At BC Cancer, only those patients with PD-L1 high are eligible for first line (1L) ICI monotherapy, offering an opportunity to study potential new biomarkers in a relatively unbiased cohort of patients treated by ICI without chemotherapy. DetermaIO (IO score) is a 27-gene RT-qPCR immuno-oncology assay that classifies the tumor immune microenvironment (TIME) as IO+ or IO- and has been previously shown to associate with clinical benefit to ICI therapy in multiple tumor types. <h3>Methods</h3> All available FFPE blocks were assembled for ECOG≤2 patients treated with at least one cycle of ICI monotherapy in the 1L (required to be PD-L1≥50%) or later line (2L+). DetermaIO was performed using a CAP/CLIA validated RT-qPCR assay for cases where sufficient tissue was available. IO score classification was analyzed for association with PFS and OS in patients treated in the 1L. <h3>Results</h3> Considering the entire cohort of 147 patients, DetermaIO was significantly associated with OS (HR=0.68, 95%CI 0.47–0.89, p=0.042) and PFS (HR=0.62, 95%CI 0.43–0.88, p=0.0069). When examining the cohort by line of therapy, 78 (53%) were treated in 1L with ICI monotherapy and were all PD-L1 high. DetermaIO in this subgroup was significantly associated with PFS (HR=0.55, 95%CI 0.32–0.94, p=0.028) and demonstrated meaningful clinical benefit when measuring OS (HR=0.60, 95%CI 0.34–1.06, p=0.078). The objective response rate in the 1L subgroup was 53% for IO+ (2CR, 28PR out of 56 patients) and 23% for IO- (5PR out of 22 patients). The net reclassification rate of IO- amongst the PD-L1 high 1L group was 54.5% (12/22, p<0.01) for response. <h3>Conclusions</h3> Retrospective analysis of outcomes of aNSCLC patients treated 1L with ICI monotherapy found that DetermaIO was significantly associated with PFS and trended towards significance for OS. First-line PD-L1 high patients who were IO- had significantly worse outcomes for PFS than PD-L1 high IO+ patients potentially informing the selection of combination therapy in PD-L1 high patients. These data confirm and expand previous studies of DetermaIO in advanced NSCLC and suggest IO score classification may offer significant incremental information for helping to make complex treatment decisions in aNSCLC. <h3>Ethics Approval</h3> This study was approved by the Research Ethics Board (REB) of University of British Columbia (H20–02635). Individual consent for this retrospective analysis and the use of tumor samples for the IO score assay was required for live patients. Consent was waived by the REB for deceased patients.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".