Abstract 4682: Sunitinib (SU) in advanced NSCLC: Correlation of circulating biomarkers with clinical outcome
Bibliographic record
Abstract
Abstract Introduction SU is an oral multitargeted inhibitor of VEGFRs, PDGFRs, KIT, FLT3, CSF-1R and RET. Antitumor activity and safety of SU in NSCLC were reported in phase II trials. We investigated potential biomarkers of clinical outcome with SU in NSCLC. Methods Patients (pts) with Stage IIIB/IV NSCLC in two phase II trials received single-agent SU either as maintenance therapy (n=66: 50 mg/day on Schedule 4/2 [6-week cycle: 4 weeks on followed by 2 weeks off treatment]) following first-line paclitaxel/carboplatin, or as refractory treatment (n=63: 50 mg/day on Schedule 4/2 for up to 9 cycles, or n=47: 37.5 mg/day on a continuous daily dose [CDD] schedule of 4-week cycles for up to 13 cycles). Soluble (s) plasma proteins (VEGF-A, VEGF-C, sVEGFR-2, sVEGFR-3, sE-selectin, sKIT) assayed by ELISA pre-dose and at regular intervals in both trials were analyzed for association with efficacy. Results In the trial of SU maintenance therapy, median progression-free survival (PFS) and overall survival (OS) were greater for pts with sVEGFR-3 levels < median ratio to baseline (BL) (n=10) vs. pts with sVEGFR-3 levels ≥ median ratio to BL (n=11) at Cycle 3 Day 1 (PFS: hazard ratio [HR] 3.6, 95% CI 1.19-11.13, p=0.0153; OS: HR 3.8 [1.35-10.88] p=0.0074). Median PFS was also greater for pts with VEGF-C levels ≥ median ratio to BL (n=15) vs. pts with VEGF-C levels < median ratio to BL (n=15) at Cycle 2 Day 28 (HR 0.3 [0.12-0.80] p=0.0109), a similar but non-significant trend was observed for OS. While PFS did not differ based on sE-selectin levels, pts with sE-selectin levels < median ratio to BL had greater median OS vs. pts with sE-selectin levels ≥ median ratio to BL at Cycle 3 Day 1 (n=8 vs. n=8: HR 4.4 [1.09-17.56] p=0.0241) and end of treatment (n=8 vs. n=9: HR 3.4 [1.10-10.41], p=0.0251). sVEGFR-3 median ratios to BL for pts with complete response (CR), partial response (PR) or stable disease (SD) ≥6 weeks (n=15) were lower vs. progressive disease (PD, n=5) at Cycle 3 Day 1 (0.57 vs. 0.92 p=0.029). In the trial of SU in refractory NSCLC, for Schedule 4/2 VEGF-A mean ratios to BL were higher in pts with CR/PR/SD ≥6 weeks (n=24) vs. PD (n=23) at Cycle 1 Day 14 (4.1 vs. 2.5 p=0.046). sVEGFR-2 and sVEGFR-3 mean ratios to BL were lower in pts with CR/PR/SD ≥6 weeks vs. PD at Cycle 2 Day 28 (0.4 [n=22] vs. 0.6 [n=8] p=0.03) and Cycle 1 Day 28 (0.3 [n=23] vs. 0.4 [n=19] p=0.043), respectively. In the CDD cohort, sVEGFR-2 mean ratios to BL were greater in pts with PFS ≥ median vs. PFS < median at Cycle 3 Day1 (0.5 [n=13] vs. 0.4 [n=4] p=0.032). Mean BL sVEGFR-3 levels were lower in pts with PR/SD vs. PD (41,498 [n=10] vs. 56,210 [n=20] pg/mL p=0.02). No significant difference in sKIT BL levels or ratios to BL were observed and no further strong correlations were apparent for other analytes in either cohort. Conclusions Soluble protein levels at some timepoints correlate with clinical outcome in advanced NSCLC pts treated with SU; low sVEGFR-3 levels were associated with favorable outcome in all analyses. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4682.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.001 | 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".