Clinical outcomes for plasma-based comprehensive genomic profiling versus tissue testing in advanced lung adenocarcinoma.
Bibliographic record
Abstract
9027 Background: Somatic genomic testing is recommended by numerous expert guidelines to inform targeted therapy treatment for patients with advanced lung adenocarcinoma (aLUAD). The NILE study was a prospective observational study that demonstrated non-inferiority of cell-free circulating tumor DNA (cfDNA)-based tumor genotyping compared to tissue-based genotyping to find targetable genomic alterations in patients with newly diagnosed aLUAD. As the cohort has matured, clinical outcomes data can now be reported. Methods: This prospective, multicenter North American study (NCT03615443) enrolled patients with previously untreated aLUAD who had standard of care (SOC) tissue genotyping performed and concurrent comprehensive cfDNA analysis using the commercially available Guardant360 assay (Guardant Health, Redwood City, CA). After 12 months of study enrollment, objective response rates, disease control rate, and time to treatment data were collected for patients with targetable genomic alterations, as defined by NCCN guidelines, who were treated with physician’s choice of therapy. Results: Among 282 patients on the study, 89 (31.6%) had an actionable biomarker detected by tissue (21.3%) and/or cfDNA (27.3%) analysis. Sixty-one (68.5%) of these patients were treated with an FDA-approved targeted therapy guided by somatic genotyping results ( EGFR, ALK, ROS1). Thirty-three patients were eligible for clinical response evaluation and demonstrated an objective response rate of 58% and disease control rate of 94%. Twenty-five (76%) achieved a durable response > 6 months; 17 (52%) achieved a durable response > 12 months. Patients responded to targeted therapy regardless of the variant allele frequency of the target alteration. The time to treatment (TtT) was significantly faster for cfDNA-informed biomarker detection as compared to tissue genotyping (median 18 vs 31 days, respectively; p = 0.0008). Conclusions: This is the first prospective community-based study to find that cfDNA detects guideline-recommended biomarkers at a rate similar to tissue genotyping, and therapeutic outcomes based on plasma-based comprehensive genomic profiling are comparable to published tissue-based targeted therapy clinical outcomes. The NILE study complements and confirms findings in the prospective FLAURA and SLLIP studies, which exclusively enrolled at academic sites. Clinical trial information: NCT03615443.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".