Abstract LB107: Association of circulating free DNA (cfDNA) maximum variant allele frequency (mVAF) levels with clinical outcomes in patients (pts) with metastatic nonsquamous non-small cell lung cancer (NSCLC) treated with pembrolizumab (pembro) + chemotherapy (chemo) in the phase 2 KEYNOTE-782 trial
Bibliographic record
Abstract
Abstract Background: The phase 2 KEYNOTE-782 trial (NCT03664024) was designed to prospectively evaluate plasma-derived biomarkers of response to first-line pembro + chemo in pts with metastatic nonsquamous NSCLC. This exploratory analysis of KEYNOTE-782 evaluated the association of cfDNA mVAF levels with clinical outcomes. Methods: Adults with untreated stage IV nonsquamous NSCLC received pembro 200 mg Q3W + chemo (pemetrexed + carboplatin or cisplatin). cfDNA was isolated from plasma samples collected at baseline (BL) and cycle 2 (C2) and sequenced using a targeted NGS-based assay previously used to assess blood tumor mutational burden from cfDNA for the primary analysis. cfDNA mVAF was quantified for each patient. The associations of BL cfDNA mVAF (all pts) and change in cfDNA mVAF from BL at C2 (pts with ≥1 detectable variant at BL; cfDNA+) as continuous variables with ORR, PFS, and OS were evaluated; 1-sided α was prespecified at 0.05 after multiplicity adjustment. ORR, PFS, and OS were also descriptively evaluated by cfDNA bins (BL mVAF, >0 vs 0; mVAF change from BL, ≥median vs 0 (n = 83) vs 0 (n = 18), ORR (95% CI) was 38.6% (28.1-49.9) vs 55.6% (30.8-78.5), median PFS (95% CI) was 6.6 mo (4.9-9.0) vs 19.7 mo (9.8-not reached [NR]), and median OS (95% CI) was 13.6 mo (9.4-22.5) vs 31.6 mo (20.1-NR). Larger reductions in mVAF from BL at C2 were associated with improved ORR, PFS, and OS (P <0.05, each). The AUROC for discriminating response was 0.69 (95% CI, 0.57-0.82). After adjustment for best overall response, change in mVAF from BL at C2 was not associated with PFS or OS (P >0.05). In a descriptive evaluation for pts with a mVAF change from BL at C2 ≥median of 0.15 (n = 37) vs Citation Format: Jair Bar, Emilio Esteban, Delvys Rodríguez-Abreu, Santiago Ponce-Aix, Zsuzsanna Szalai, Enriqueta Felip, Maya Gottfried, Mariano Provencio Pulla, Andrew Robinson, Andrea Fülöp, Suman Bannur Rao, D. Ross Camidge, Giovanna Speranza, Nathan Hunkapiller, Robert McDaniel, Byoungsok Jung, David Burkhardt, Ruth Mauntz, Cai Chen, Carol Pena, Razvan Cristescu, Elisha J. Dettman, Steven M. Townson, Julie Kobie, Tibor Csőszi. Association of circulating free DNA (cfDNA) maximum variant allele frequency (mVAF) levels with clinical outcomes in patients (pts) with metastatic nonsquamous non-small cell lung cancer (NSCLC) treated with pembrolizumab (pembro) + chemotherapy (chemo) in the phase 2 KEYNOTE-782 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB107.
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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 | 0.001 | 0.002 |
| 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".